Pain

People with SCI often have some form of pain that compromises quality of life and the ability to carry out many activities. Pain can result from both damage to the spinal cord itself and the lifestyle imposed by the neurological damage (e.g., wheelchair transfers, etc). Unfortunately, efforts to manage such pain have been challenging.

PREVALENCE OF SCI PAIN

Numerous studies document the high prevalence of pain in individuals with SCI, including the following:

1) A survey of 380 individuals with SCI by Dr. P. Fenollosa et al indicated that 66% had experienced chronic pain lasting longer than six months. The most common type of pain was deafferentation or phantom pain due to the loss of sensory input into the central nervous system.

2) Dr. S. Stormer and colleagues (Germany) reported that 66% of 901 surveyed patients with SCI had either pain or pain-related sensations called dysesthesia (uncomfortable, abnormal sensations such as burning, wetness, itching, electric shock, and pins and needles). Sixty-one percent of them rated their pain intensity 7+ on a scale ranging from 0 (no pain) to 10 (as bad as it can get). Seventy-five percent described the pain “as rather or very distressing.” In these patients, 86% reported that the pain was located below the spinal-cord-injury lesion or in the transition zone surrounding it.

3) Dr. A. Ravenscroft and associates (United Kingdom) sent a questionnaire to 216 individuals with SCI listed on a regional SCI database. Of the 67% who responded, 79% indicated that they currently suffered from pain, with 39% describing it as severe. The survey results suggested that complete injury was more likely than incomplete injury to result in chronic pain.

4) Dr. Nanna Finnerup and colleagues (Denmark) mailed a questionnaire to 436 outpatients of a SCI rehabilitation center, of whom 76% responded. The time since injury in these individuals ranged from 0.5 to 39 (average 9.3) years. Overall, 77% of the respondents reported having pain or unpleasant sensations (e.g., dysesthesia), including 67% reporting pain or unpleasant sensations below the area of injury. Nearly half reported that pain-related sensations could be triggered by stimulation of the skin by non-noxious processes that do not normally provoke pain (a condition called allodynia).

5) Dr. P. Siddall et al. (Australia) followed the evolution of pain in 73 patients for five years after injury. Eighty-one percent reported the presence of pain, the most common form being musculoskeletal pain (59%), followed by at-level neuropathic pain (41%), below-level neuropathic pain (34%), and visceral pain (5%), respectively. [These different forms of SCI-related pain are discussed below.]

6) Dr. D. Cardenas et al (USA) reviewed the health records of 7,379 individuals with SCI, who had been entered in a national SCI database. Data analyses indicated that the prevalence of pain remained fairly constant over time, for example, 81% reporting pain one year after injury and 83% 25 years after injury. Although no gender difference was noted, pain prevalence was lower in nonwhites.

7) Dr. C. Donnelly and associates (Canada) examined the records of 66 individuals with SCI who had been consecutively admitted to a tertiary rehabilitation center. Six months after discharge, 86% reported pain, with 27% reporting pain severe enough to affect many or most activities.

SCI PAIN CLASSIFICATION

There are many different forms of SCI-associated pain. For example, the pain can be located above the level of neurological injury, at or near the injury level, or below the injury level. In addition, the pain can be either nociceptive or neuropathic in origin. Nociceptive pain occurs from damage to non-neural tissues, such as bones, connective tissue, muscle, skin, or other organs, that are still partially or fully innervated. It can be mechanical or musculoskeletal in nature, or arise from damage to or irritation of internal visceral organs affected by SCI.

As the name implies, neuropathic pain results from damage to neural tissue either within the peripheral (nerves outside of the brain and spinal cord) or central nervous system. Two common forms of SCI-neuropathic pain are central and radicular pain. The former is caused by damage to the spinal cord itself. The latter is caused by damage to nerve roots where they connect to the spinal column due to damage from the initial injury or impingement by bone fragments or disk or scar material.

Studies suggest that there are changes in the properties of nerve cells close to the injury site, including 1) increased responsiveness to peripheral stimulation, 2) more background activity, and 3) extended neuron firing following stimulation. Overall, injury results in altered neurotransmission and, as such, the firing properties of spinal neurons.

As indicated in the table, Drs. Thomas Bryce and Kristjan Ragnarsson (USA) have developed a SCI pain classification system that integrates these concepts into 15 different types of pain.

For illustration sake, a number of these categories are amplified below:

Type 1: An example of above-level, nociceptive pain of mechanical or musculoskeletal origin is shoulder pain resulting from transfers, rotator cuff injuries, etc.

Type 2: An example of this sort of pain is a headache from autonomic dysreflexia (see glossary).

Type 4: Above-level, compressive neuropathic pain is generated from impingement of a specific peripheral nerve, an example being carpel tunnel syndrome resulting from the repetitive actions of wheelchair pushing.

Type 6: At-level nociceptive pain of mechanical or musculoskeletal origin is similar to Type 1 pain except located nearer the level of injury, e.g., shoulder pain in the case of a cervical injury.

Type 7: At-level nociceptive pain of visceral origin results from damage, irritation, or distension of internal organs. An example is pain resulting from fecal impaction or bowel obstruction.

Type 8: At-level neuropathic, central pain is caused by damage to the spinal cord. In thoracic injuries, central pain is often characterized by tightness, pressure, or burning; and in cervical injuries by numbness, tingling, heat, or cold. The formation of a fluid-filled syringomyelia cavity within the spinal cord often causes central pain.

Type 9: At-level neuropathic, radicular pain is caused by damage to nerve roots at their connection to the spinal column. Such damage is often due to the initial injury or impingement by bone fragments, disk material, or scar tissue. Pain is often described as radiating, stabbing, shooting, or electric-shock like.

Type 10: At-level compressive, neuropathic pain is similar to Type 4 pain, except located nearer to the injury site. An example would be repetitive-motion-created carpal tunnel syndrome in an individual with a cervical injury.

Type 11: With complex regional pain syndrome, pain is 1) not limited to the region of a single peripheral nerve or nerve root, 2) out of proportion to what is expected, and 3) associated with edema, skin blood-flow abnormality, or irregular activity of the nerves that stimulate sweat glands (called sudomotor activity). It is associated with diffuse hand pain, swelling and stiffness.

Type 12: Nociceptive mechanical or musculoskeletal pain below the level of injury occurs in individuals with incomplete injuries or complete injuries with a zone of partial preservation extending to the level of the pain. It is often associated with spasticity.

Type 13: Below-level, nociceptive visceral pain is primarily due to damage, irritation, or distension of internal organs. It occurs in individuals with injuries above the mid-thoracic region and is often vague and poorly localized in nature.

Type 14: Below-level, neuropathic central pain is caused by damage to the spinal cord. It is often regional in nature affecting large areas such as the anal region, the bladder, the genitals, the legs or even the entire body below the injury level. The pain has been described as burning or aching and often continuous in presence.

TREATMENTS FOR SCI-RELATED PAIN

Many approaches have been developed for treating SCI-related pain, ranging from the pharmaceutical to the surgical to the alternative. In general, these approaches have had modest success at best, often depend upon the specific pain that is manifesting, and are frequently accompanied by significant side effects. Overall, pain management is a challenging problem, which will require the continued effort of clinicians and researchers to develop effective solutions.

PHARMACEUTICAL APPROACHES

For better or worse, pharmaceutical approaches remain the cornerstone of most SCI-pain-controlling strategies. Many different drugs developed for a variety of purposes have been used in an effort to ameliorate SCI pain, including anticonvulsants, analgesics, antispastics, antidepressants, nonsteroidal anti-inflammatory drugs, etc.

Anticonvulsant Drugs

Anticonvulsants are a diverse group of drugs developed for the treatment of epileptic seizures. They have been adopted for use in treating SCI pain because scientists have noted a similarity between the underlying physiology or biochemistry observed in seizure disorders and neuropathic pain, both of which involve abnormal firing of neurons. Several studies summarizing the use of a number of anticonvulsant drugs to treat SCI pain are provided below:

1) Initially developed to treat epileptic seizures, gabapentin has been used to manage neuropathic pain after SCI. Structurally related to a key neurotransmitter called GABA (gamma-amino butyric acid), evidence suggests that gabapentin interferes with the transport of calcium ions into neurons, a process involved in the excitation of neurons.

GABA	Gabapentin

A) Dr. Funda Levendoglu and associates (Turkey) examined the effectiveness of gabapentin in ameliorating neuropathic pain in 20 subjects (13 males, 7 females) with complete paraplegia. The subjects ranged in age from 23 to 62 (mean 36) years, and the time since injury varied from seven to 48 months.

The study was designed as a prospective, randomized, double-blind, placebo-controlled, crossover clinical trial. Basically, under this study design, an equal number of subjects were randomized to receive either gabapentin or placebo in identical capsules. In the first four weeks, the subjects received increasing doses of the drug/placebo until the maximum dosing level was achieved, which was maintained for four more weeks. After a two-week washout period in which no drug or placebo was administered, treatments were reversed for another four weeks; i.e., gabapentin-treated subjects now received placebo and vice versa.

Pain was measured by several different scales, including the Visual Analog Scale (VAS). With this scale, subjects rated their pain levels on a scale ranging from 0 (no pain) to 100 (worst pain imaginable). As can be seen from the table, the pain levels of gabapentin-treated subjects declined significantly over the treatment period relative to placebo.

With the Neuropathic Pain Scale, subjects rated their pain levels on a scale from 1 to 10 for different aspects of neuropathic pain, including that described as sharp, hot, dull, cold, sensitive, itchy, unpleasant, deep or surface pain. Any score above 4 was considered moderate to severe pain. Over time, gabapentin treatment provided a statistically significant reduction in pain for all aspects except for the itchy, dull, sensitive, and cold categories. For example, before gabapentin treatment, the score for deep neuropathic pain averaged 7.0, but after eight weeks of treatment, it averaged only 3.5.

Sixty-five percent and 25% of the gabapentin and placebo-treated patients, respectively, reported various side effects, such as nausea, vomiting, weakness, edema, vertigo, sedation, headache, diarrhea, blurred vision, muscle twitching, and itching.

B) Dr. T.P. To et al (Australia) retrospectively reviewed the health records of 38 individuals with SCI to assess gabapentin’s potential to alleviate neuropathic pain. Age averaged 47 (range 15 -75) years. There were 28 males; 19 and 16 with paraplegia and 16 tetraplegia, respectively; and three times more chronic than acute (< six months) injuries. The review indicated periodic assessments of pain using the Visual Analog Scale, which, in this case, ranged from 0 (no pain) to 10 (worse pain imaginable).

Using this scale, 29 of the 38 patients had some degree of pain relief due to gabapentin. There were eight reports of adverse effects, most notably drowsiness. Eleven patients had pain levels assessed at one, three, and six months after starting gabapentin treatment. As indicated in the table, average pain levels in these 11 patients decreased form 8.9 to 4.0 after six months.

C) Dr. Sang-Ho Ahn and associates (Korea) evaluated gabapentin’s effectiveness in treating neuropathic pain in 31 subjects with SCI. These individuals were divided into two groups: 1) 13 whose duration of pain was less than six months and 2) 18 whose duration of pain had lasted more than six months. Subject age averaging 45-46 years old; Group 1 was composed of seven and six individuals with tetraplegia and paraplegia, respectively; and Group 2 included six and 12 individuals with tetraplegia and paraplegia, respectively.

Before gabapentin treatment, all patients had been treated with a variety of other pain medications without improvement. While continuing these preexisting medication regimens, increasing gabapentin doses were administered to the patients until a maintenance dose was reached after 18 days. This maintenance dose was continued for eight weeks. Pain was periodically measured using the aforementioned VAS scale. In addition, interference of sleep by pain was assessed on a scale ranging from 0 (no interference) to 10 (unable to sleep because of pain).

Of the 31 subjects initially recruited, 25 completed the study. For both groups, the amount of pain and sleep interference was significantly reduced after eight weeks of gabapentin treatment. The reduction was greater in Group 1 (pain duration < 6 months) than Group 2 (pain duration > 6 months). Specifically, the average pain score for Group 1 decreased from 7.3 to 3.0 by eight weeks, whereas the Group 2 score decreased from 7.6 to 5.1. In the case of sleep interference, the Group-1 average score decreased from 5.7 to 1.8, while the Group-2 score declined from 5.9 to 4.2.

D) In an effort to determine gabapentin’s long-term effectiveness, Dr. John Putzke and colleagues (USA) identified 31 patients who had been treated with the drug for up to three years. Of these 31 patients, 76% were men, 67% had paraplegia, 76% had incomplete injuries, and 86% reported pain at or below the level of their injury.

Twenty seven of the initial 31 identified patients were contacted six months after initiating gabapentin treatment. Of these 27, six had discontinued treatment due to intolerable side effects. The remaining 21 rated their pain on a scale raging from 0 (no pain) to 10 (most excruciating pain imaginable). Fourteen (67%) of these 21 patients reported a favorable reduction in pain over this six-month time period defined as a 2+ point reduction on this 0-10 scale. Of these 14 subjects, 11 were contacted three years after initiating gabapentin treatment. Ten of these 11 continued to report pain-relieving benefits that they attributed to gabapentin. Side effects included fatigue, forgetfulness, edema, gastrointestinal upsets, sedation, blurred vision, dry mouth, constipation, and dizziness.

2) Pregabalin is also an anticonvulsant drug specifically developed to treat neuropathic pain as well as epileptic seizures. Like gabapentin, pregabalin is structural analog of the GABA neurotransmitter. It also apparently works by affecting calcium ion influx into neurons, which, in turn, modulates the firing of neurons involved in triggering pain sensations.

A) Dr. Philip Siddall and colleagues (Australia) evaluated pregablin’s effectiveness in treating central neuropathic pain in subjects recruited from eight Australian centers. In this study, 137 patients were randomized to receive either pregablin (70 patients) or placebo (67 patients) for 12 weeks. This was a double-blind study, meaning neither patient nor physician knew who was receiving the drug as opposed to the placebo. In the pregabalin-treated group, age averaged 50 years; 60% were men; and 59% and 41% had paraplegic and tetraplegic injuries, respectively. All subjects had been injured for at least a year and had central neuropathic pain lasting three months continuously or alternatively six months intermittently. Subjects were allowed to continue preexisting pain-medication regimens (~70% of subjects), except for gabapentin, which, due to its similarity to pregablin, had to be discontinued a least week before starting the study.

Starting the week before treatment (i.e., baseline assessment) and throughout the 12 week treatment period, all subjects rated their pain upon awakening in the morning for the preceding 24 hours on a scale from 0 (no pain) to 10 (worst possible pain). Using a similar scale, they also rated the degree to which the pain interfered with sleep.

The pain level in the pregablin-treated subjects decreased from 6.5 before treatment to 4.2 at the end of the study. In contrast, the pain levels for placebo-treated individuals only decreased from 6.7 to 6.3. Forty-two percent of the pregablin-treated subjects had at least a 30% reduction in pain compared to only 16% for the placebo-treated individuals. In addition, 22% of the pregablin-treated subjects had at least a 50% reduction in pain compared to only 8% for those who were treated with placebo.

Furthermore, pregablin-treated patients had a similar reduction in sleep problems. For example, in contrast to the placebo-treated subjects who had only a minimal reduction in sleep interference over the treatment period (4.9 to 4.7), the sleep interference score decreased from 4.2 to 2.8 in pregablin-treated subjects.

The most frequently reported adverse effects were drowsiness (41%), dizziness (24%), edema (20%), weakness (16 %), dry mouth (16%), and constipation (13%).

B) Dr. Jan Vranken and associates (The Netherlands) examined pregabalin’s effectiveness in a randomized, double-blind, placebo-controlled clinical trial. The investigators recruited 40 subjects with a variety of neurological disorders predisposing them central neuropathic pain, including 21 with complete and incomplete spinal cord injuries. These individuals were randomized to receive either pregabalin or placebo daily for four weeks. In addition, they were allowed to continue any preexisting pain-medication regimens if it had been stable in nature. The exception was gabapentin, which had to be discontinued at least three days before study initiation. To be enrolled, all subjects had to have a pain level of at least 6 using the previously described 0-10 pain-intensity scale.

As shown in the graph, pain intensity was significantly less in those treated with pregablin. Specifically, although pain levels in placebo-treated individuals essentially remained unchanged over the four-week trial period, pain in the pregabalin-treated subjects decreased from 7.6 to 5.1, a decrease the investigators described as a reduction from severe to modest. Seven pregabalin-treated subjects had a reduction in pain of more than 50% compared with only one placebo-treated subject. Roughly equal adverse effects were observed for both the pregabalin and placebo group, indicating that, at least in the case of this study, pregabalin-related side effects were minimal.

3) Lamotrigine is another anticonvulsant drug used to treat epilepsy, bipolar disorder, and, secondarily, neuropathic pain. Unlike gabapentin and pregabalin, it is not a structural analog of the GABA neurotransmitter.

Dr. Nanna Finnerup and associates (Denmark) evaluated lamotrigine’s pain-treating effectiveness in 30 individuals with SCI-related neuropathic pain below the level of the lesion. To be enrolled, subjects had to have a 3+ pain level on the 0 (no pain) to 10 (worst imaginable pain) scale discussed previously. The study was designed as a randomized, double-blind, placebo-controlled, crossover trial. Specifically, subjects were randomized to receive either lamotrigine or placebo for nine weeks, after which there was a two-week washout period in which no drug/placebo was given. When this washout period was finished, treatments were reversed and the lamotrigine-treated subjects now received placebo for nine weeks, and the placebo-treated individuals were given the active drug.

Of the 30 enrolled patients, 22 completed the study. Of these remaining subjects, age ranged from 27 to 63 (average 49) years; 18 were men; and 9, 11 and 2 had cervical, thoracic, and lumbosacral injuries, respectively (including both complete and incomplete injuries). Study results indicated that lamotrigine only reduced pain levels in those with incomplete injuries. Specifically, for these individuals, the difference in pain reduction between drug- and placebo-treated averaged a modest 25%. The drug had had no statistical significant effects for those with complete injuries. The number of adverse side effects were comparable in both lamotrigine and placebo groups.

Antidepressants Drugs

Several antidepressant drugs have been used to treat SCI pain, including the following:

1) Amitriptyline treats depression symptoms by raising the levels of naturally occurring substances in the central nervous system. For example, like other antidepressants, amitriptyline increases serotonin, a key mood-influencing neurotransmitter. In addition to depression, the drug has been used to treat pain generated from a variety of disorders, including SCI.

In a 2007 article, Dr. Diana Rintala and colleagues (USA) compared the effectiveness of amitriptyline relative to gabapentin in ameliorating chronic, SCI-associated neuropathic pain. Thirty-eight individuals with SCI were randomized to receive either amitriptyline, gabapentin, or an active placebo (Benadryl, an over-the-counter allergy medication). After a baseline interval in which subjects received no pain medications, one of these three agents was administered for nine weeks. This was followed by a one-week washout period in which no drugs were administered. Thereafter, a different drug was administered for another nine-week period, e.g., the amitriptyline-treated individuals were now given gabapentin or placebo, etc. After another washout period designed to remove residues from the body of the previously administered drug, the third agent would be given, e.g., the subjects who had been initially given amitriptyline followed by gabapentin were now treated with placebo, etc.

Of the 38 subjects who started the study, 22 completed the study. Average age was 43 (range 22-65) years; time since injury averaged 13 (range 1-33) years; and 90% were men. Subjects included individuals with both tetraplegia and paraplegia, as well as complete and incomplete injuries.

Pain was periodically assessed using the previously discussed VAS measure which subjectively rated pain on scale ranging from 0 (no pain) to 10 (worst possible pain). In addition, depression levels in subjects were periodically evaluated using another subjective scale.

The overall results indicated that amitriptyline was more effective than gabapentin in relieving pain. Specifically, after eight weeks of treatment, pain levels on the 0-10 VAS scale averaged 3.5 for amitriptyline-treated subjects, 4.8 for gabapentin-treated subjects, and 5.1 for placebo-treated subjects. Underscoring the relationship of pain to depression, amitriptyline’s pain-relieving benefits were greater in those individuals who started the study with the most depression. Documented side effects for amitriptyline included mouth dryness, constipation, increased spasticity, and painful urination.

Different results were observed in an earlier study (2002) carried out by Dr. Diana Cardenas and colleagues (USA). In this study, 44 and 40 subjects were randomized to receive either escalating doses of amitriptyline or placebo, respectively, for six weeks. Because a common side effect of amitriptyline is dry mouth, an active placebo (i.e., not inert) was chosen that also produced dry mouth (specifically, benztropine, a drug used for Parkinson’s disease). This was done to preserve the study’s blinded nature so that subjects could not readily distinguish amitriptyline from the placebo.

In the amitriptyline-treated subjects, age ranged from 21 to 63 (average 41) years; 59%, 39%, and 2% had cervical, thoracic, and lumbar/sacral injuries, respectively; approximately half had complete injuries; and 73% were men. The average time since injury was about 13 years.

As in the previously discussed studies, pain was periodically evaluated on a scale ranging from 0 (no pain) to 10 (as bad as could be). In this study, no statistically significant difference in pain levels was observed between the amitriptyline and placebo-treated groups. One possible reason for the different outcomes compared to the previous discussed study is that the Rintala study was limited to individuals with neuropathic pain while the Cardenas study included a variety of types of SCI-related pain, each of which may respond differently to various medications.

Analgesics

A number of traditional painkilling drugs have demonstrated some effectiveness in treating SCI-related pain, including the following:

1) Lidocaine has a variety of medical applications, pain killing and otherwise. Most commonly it has been used as a topical agent to relieve itching, burning, and pain from skin inflammation; or through injection as a dental numbing agent or as a local anesthetic for minor surgery. In addition, it has been intravenously administered to treat abnormal heart rhythms, i.e., arrhythmias. Physiologically, lidocaine affects the flux of sodium ions into neurons needed to propagate nerve signals. By so doing, scientists theorize that the neuronal hyperexcitability that characterizes SCI neuropathic pain may be dampened.

A) In 2005, Dr. Nanna Finnerup et al (Denmark) reported the results of a study treating 24 subjects with neuropathic pain at or below the level of the injury with lidocaine. Subjects were randomized to receive either an intravenous infusion of lidocaine or saline solution. Subject age ranged from 28 to 66 years; 17 were men; 9, 12, and 3 had cervical, thoracic, and lumbosacral injuries/dysfunction, respectively; and the sample included a range of both complete and incomplete injuries. Among other measures, pain was assessed on a subjective 0-100 scale before infusion, and 25 and 35 minutes after infusion was started. After at least six days, treatments were reversed; i.e., lidocaine-treated subjects now received the placebo infusion and vice versa.

The average difference in pain reduction between lidocaine- and placebo-treated subjects was 36%. Eleven lidocaine-treated subjects had at least a 33% reduction in pain compared to only two placebo-treated subjects. Nineteen lidocaine-treated subjects experienced various adverse side effects, including drowsiness, dizziness, impaired speech, lightheadedness, blurred vision, etc.

B) In 2000, Dr. N. Attal and associates (France) evaluated the effectiveness of intravenously administered lidocaine in alleviating pain in 16 individuals with stroke (6) or spinal cord injury/dysfunction (10). The study focused on central pain, including spontaneous ongoing pain and evoked pain such as allodynia produced by stimuli that does not normally provoke pain (such as skin brushing; see introductory discussion. Of the 16 patients enrolled, 10 were women and six men; mean age was 55; and duration of pain averaged 47 months. Subjects were randomized to receive either a 30-minute, intravenous infusion of lidocaine or saline solution. Among other measures, pain levels were assessed before treatment and periodically thereafter using a subjective pain scale ranging from 0 (no pain) to 100 (worst possible pain).

When compared to controls, the lidocaine-treated subjects had statistically significant less spontaneous pain at the end of the treatment and for up to 45 minutes afterwards. Specifically, the pain levels in lidocaine-treated subjects decreased from 61 to 31 while the pain levels in placebo-treated subjects decreased only to 46. However, after 45 minutes, the difference in pain levels between the two groups diminished. Similarly, lidocaine-treatment reduced the intensity of allodynia for 30 minutes after treatment was completed. Few, if any, long-term benefits were observed. The investigators concluded that “in least in patients with central pain, long-term analgesic effects of lidocaine are uncommon.” Adverse side effects included lightheadedness/dizziness, drowsiness, nausea/vomiting, impaired speech, malaise, etc.

C) In 1991, Dr. P. G. Loubser and associates (USA) evaluated lidocaine’s pain-killing effectiveness in 21 individuals with chronic SCI. In this study, subjects were randomized to receive either lidocaine or saline placebo by injection into the lumbar subarachnoid space (i.e., the area filled with cerebrospinal fluid). After a sufficient washout period, treatments were reversed. Subject age ranged from 18 to 58 (average 42) years; 14 subjects were men; and 5, 14, and 2 had cervical, thoracic, and lumbar injuries, respectively. All subjects had had chronic pain of at least six months duration.

Pain was assessed before and periodically after treatment using a variety of assessments. Thirteen lidocaine-treated subjects showed an average 38% reduction in pain lasting on average about two hours. Eight lidocaine-treated subjects showed no changes. In a many subjects, lidocaine affected the distribution of pain throughout the body and nature of the pain sensations. In a number of cases, there were spinal canal blockages, which prevented the lumbar-region-administered lidocaine from reaching and exerting painkilling effects in areas above the blockage.

2) Ketamine has been primarily used to generate brief periods of anesthesia, during which the patient feels dissociated or separated from the body. Due to these altered-consciousness effects, the drug has a history of substance abuse. Ketamine has also been medically used to treat pain, depression, and asthmatics or individuals with chronic obstructive airway disease. Ketamine interferes with a key neurotransmission process involved in generating pain.

In 2004, Dr. Ann Kvarnstrom et al (Sweden) evaluated the effectiveness of intravenous ketamine and lidocaine in treating below-level, neuropathic pain. Ten individuals with SCI were randomized to receive 40-minute intravenous infusions of either ketamine, lidocaine, or saline solution. After at least four days, one of the other agents was similarly administered, and after another four days, the final agent was given. Of the 10 subjects, nine were men; age ranged from 30-60 (average 45) years; 1 and 9 had complete and incomplete injuries, respectively; and 5, 4, and 1 had cervical, thoracic, and lumbar injuries, respectively. The average pain duration in subjects had been nine years.

Pain was evaluated before the start of the infusion and 15, 45, 60, 120 and 150 minutes afterwards using the subjective 0 (no pain) to 10 (worst pain imaginable) scale. Using this scale, the average pain reduction was 38% for the ketamine-treated subjects, 10% for the lidocaine-treated subjects, and 3% for the placebo-treated subjects. Five of the ketamine-treated subjects had at least a 50% reduction pain compared to only one lidocaine-treated subject, and none for placebo-treated subjects. Of the responders, all claimed that ketamine was better than any other painkilling medications they had tried.

Adverse side effects were common in both the ketamine- and lidocaine-treated subjects, including drowsiness, dizziness, out-of-body sensations, changes in hearing and vision, nausea, etc.

3) Alfentanil is a potent, short-acting opioid-like agent used for surgical anesthesia.

Opioids are psychoactive, naturally occurring and synthetic molecules that bind to various receptors on the surface of neurons, including those in the spinal cord. This binding alters communication between neurons, which can mute pain perception. The most well-known example of a naturally occurring opioid-containing material is opium isolated from the poppy. Opium is the source of many painkilling and substance-abuse drugs, such as morphine, its derivative heroin, codeine. In addition, a number of opioid-like molecules are actually produced by the body, such as the endorphins – a word actually created by combining morphine and endogenous. Endorphins are neurotransmitters associated with the feel-good endorphin rush or runner’s high generated by exercise and other stimulus.

In 1995, Dr. Per Kristian Eide and associates (Norway) compared the potential of both alfentanil and ketamine to reduce pain after SCI. Nine patients were randomized to receive an intravenous infusion of either alfentanil, ketamine, or a saline placebo solution. Each drug infusion was separated by two hours. Age ranged from 25-72 (average 41) years, and all but one of the subjects were men. The sample included four cervical, four thoracic, and one lumbar injuries, and five complete and four incomplete injuries. The duration of pain in these subjects ranged from 14 to 94 months, starting in all cases less than a half year after injury.

Continuous pain and pain evoked by various stimuli was assessed using a VAS scale ranging from 0 (no pain) to 100 (unbearable pain). As shown in the graphs below, both alfentanil and ketamine reduced both types of pain. Although no severe side effects were observed, a variety of weak or modest side effects were noted for both drugs, including nausea, fatigue, dizziness, mood changes, changes in vision and hearing, feelings of unreality.

Change in Continuous Pain	Change in Evoked Pain

4) Another opioid drug, tramadol has been extensively used to treat moderate to severe pain. In addition to binding to neuronal opioid receptors, tramadol also increases levels of serotonin, a key mood-influencing neurotransmitter.

In a 2009 study, Dr. Cecilia Norrbrink and colleagues (Sweden) examined tramadol’s ability to relieve SCI-related neuropathic pain. Of the 35 recruited subjects, 23 were randomized to receive tramadol and 12 randomized to receive an identical appearing placebo agent for an average of 21 days. Twenty-eight of the 35 recruited subjects were men; 16 and 19 had tetraplegia and paraplegia, respectively; and the time since injury averaged 15 years. To avoid biasing results, subjects maintained their existing pain-relieving medications throughout the study.

Pain was evaluated using a variety of assessments, including a 0-10 pain scale which combined numerical and verbal ratings. Using this scale, subjects would periodically record various aspects of the pain they had experienced, including intensity of present pain, general pain, and worst pain. Compared to placebo, tramadol-treated subjects had statistically significant less pain in all three of these categories. In addition, tramadol-treated subjects had less anxiety and greater life satisfaction and sleep quality.

Unfortunately, there was a high incidence of adverse effects. Specifically, 21 of the tramadol-treated subjects (91%) experienced at least one adverse effect, including 11 subjects that withdrew from the study as a result. The most commonly reported adverse effects were tiredness, dry mouth, and dizziness.

5) The most abundant opioid in opium, morphine is used to treat severe pain. Due to its euphoria-producing, anti-anxiety properties, the drug has considerable addictive and substance-abuse potential. Morphine is closely related to heroin; in fact, the body converts heroin to morphine before it binds to CNS neurons. This binding produces the drug’s painkilling and psychoactive effects.

In a 2002 study, Dr. N. Attal and colleagues (France) examined the potential of intravenously administered morphine to relieve central neuropathic pain in six patients with stroke and nine with SCI. The study included nine women and six men with an average age of 54 years. All subjects had had continuous pain of duration ranging from 1.5 to 20 years. In this double-blind, placebo-controlled, crossover study, subjects were randomized to receive either an intravenous infusion of morphine or saline solution. Two weeks later, the treatments were reversed, i.e., the morphine-treated subjects now received the placebo infusion and vice versa.

Using a scale rating pain from 0 (no pain) to 100 (worst possible pain), pain intensity was assessed before treatment and 15, 30, 45, 60, 90, and 120 minutes afterwards. A variety of central-pain components were assessed, including ongoing pain and pain produced by stroking the skin with a brush (i.e., allodynia). With respect to ongoing pain, seven subjects responded to morphine. However, statistically there were no significant differences in pain levels between the morphine- and placebo-treated subjects at any point in time. In contrast, morphine produced a statistically significant reduction in the brush-induced pain lasting up to 90 minutes after treatment. In nine subjects, this evoked pain was reduced by at least 50% by the end of the injection. The investigators concluded that morphine’s painkilling benefits were probably limited to certain components of central pain. The most frequent morphine-induced side effects were drowsiness, nausea, and headaches.

Within one week of completing the study’s intravenous phase, subjects began taking sustained-release, oral morphine and started recording their pain levels daily using the aforementioned 1-100 scale. Many of the subjects eventually dropped out of the study due to unacceptable side effects of the oral morphine or the absence of pain-relieving benefits. As a result, only three subjects were still taking the oral morphine a year later. The investigators noted that morphine-responsive subjects in the study’s intravenous phase study were more likely to accrue benefits from oral morphine.

6) Clonidine has been used to treat high blood pressure, various pain conditions, attention-deficit hyperactivity disorder (ADHD), and anxiety/panic disorders.

In a 2000 study, Dr. Philip Siddall et al (Australia) examined the potential of clonidine, morphine, and a combination of the two to alleviate SCI-related neuropathic pain in 15 subjects with SCI. Ranging from 26 to 78 (average 50) years old, subjects had below-level and/or at-level neuropathic pain (see introductory discussion). In this study, the drugs were administered into the lumbar-region, intrathecal space surrounding the spinal cord. Subjects were randomized to receive clonidine, morphine, or saline via this route of administration. When either a pain-relief or side-effect response was observed, testing of the next drug was initiated the following day. After all three agents had been tested, subjects received the clonidine-morphine combination. Pain was assessed using a 0-100 rating scale and verbal pain rating (none, mild, moderate, severe, or very severe).

Neither intrathecal administration of clonidine or morphine resulted in a statistically significant reduction in pain. However, intrathecal administration of the clonidine-morphine mixture did result in statistically significant reduction. Specifically, the drug combination resulted in an average reduction of pain to 63% of the baseline score. A greater percentage of subjects with at-level, neuropathic pain obtained substantial pain relief than those with below-level neuropathic pain. The investigators suggested that this difference may be due to the different physiological origins that underlie at-level versus below-level neuropathic pain. The investigators also noted that scarring around the injury site may inhibit the migration of the drugs, which were intrathecally administered below the injury site, to cervical regions above the injury site. Given the relatively small sample size, this issue may have lessened observed pain-reduction effects.

The most common side effects were itching (morphine associated), low blood pressure (mostly clonidine associated), nausea, sedation, and hypoxia (decreased oxygen levels).

7) Capsaicin is the active component of hot peppers; it produces the hot sensation when the peppers are eaten. Medicinally, it is used in topical ointments to relieve various types of pain, e.g., backache, muscle sprains, etc. Physiologically, capsaicin-exposed neurons are depleted of a key neurotransmitter (called substance P) involved in transmitting pain signals. Basically, a sustained capsaicin burning sensation overwhelms the neuron’s capability to report pain, leading to a reduction in pain sensitivity.

In 2000, Drs. Paul Sanford and Paula Benes (USA) reported the results of treating eight individuals with localized pain at or just below the level of injury with capsaicin cream topically applied four times daily (9). Age ranging from 18 to 66, six subjects were men. All but one subject had paraplegia, and subjects were equally divided between those complete and incomplete injuries. Patients who had not responded to capsaicin (~ half of treated patients) were not among the subjects included in this discussion – i.e., the article only reported the positive results.

Subjects subjectively assessed their pain levels using a 0 (no pain) to 10 (unbearable pain) scale. As shown in the table, capsaicin-treated patients often had substantial reductions in pain levels (again, only patients who benefitted are reported). In most cases, pain levels increased again after capsaicin treatment was discontinued. Other than initial burning sensations when the cream was applied, few side effects were observed.

Anti-Spasticity Drugs

1) Baclofen is primarily used to treat spasticity associated with various neurological disorders, including SCI, multiple sclerosis, and cerebral palsy. Like several of the anti-convulsant drugs previously discussed, baclofen is structurally related to GABA, a key neurotransmitter involved in pain perception. Baclofen is given either orally or infused into the intrathecal space surrounding the spinal cord.

GABA	Baclofen

A) Because chronic pain and spasticity often co-exist, in 1992, Dr. Richard Herman and colleagues (USA) evaluated baclofen’s ability to ameliorate pain in nine individuals with spinal lesions due to SCI, MS, and transverse myelitis (disorder involving inflammation of the spinal cord) (1). Three of the subjects were men, and age ranged from 33 to 63. In a double-blind trial, seven of the nine were randomized to receive on successive days either an intrathecal infusion of baclofen or placebo. Baclofen treatment significantly reduced dysesthetic pain (see earlier discussion) in six of the seven randomized patients within 5-20 minutes of treatment. It also eliminated all spasm-related pain. After this double-blind trial had been discontinued, two additional individuals with SCI were treated with baclofen. In one, dysesthetic pain was eliminated completely, and in the other, spasm-related pain was markedly reduced. As the baclofen cleared from the body, the pain returned 8-12 hours later.

B) In 1996, Drs. Paul Loubser and Nafiz Akman (USA) reported the pain-reducing influence of baclofen treatment intrathecally administered through an implanted pump (2). Twelve treated patients had chronic pain before the intervention, including six with neurogenic pain, three with musculoskeletal pain, and three with both types of pain. All were men except one, age ranged from 21-63, and injury level was equally divided between cervical and thoracic injuries. Pain status was evaluated before pump implantation and 6 and 12 months afterwards using a variety of assessments, including the previously discussed visual analog scale rating pain from 0 to 10.

Although no statistically significant reduction in neurogenic pain was observed at either 6 or 12 months, five of the six patients with musculoskeletal pain had a significant pain reduction. The investigators concluded that “intrathecal baclofen reduces chronic pain associated with spasticity but does not decrease neurogenic pain symptoms when used at dosages aimed at controlling spasticity.”

2) The most powerful neurotoxin known, botulinum toxin is produced by the bacteria Clostridium botulinum. At one time, the fatality rate for botulinum poisoning was 60% due to respiratory muscle paralysis. In spite of its lethality, botulinum toxin has a variety of low-dose medical uses related to its ability to decrease muscle activity. By far, its most well know application is cosmetic (i.e., Botox injections) to prevent the development of wrinkles through paralyzing facial muscles.

Due to its muscle-weakening ability, botulinum toxin is also used to treat spasticity-associated hyperactive muscles and dystonia-related involuntary muscle contractions. Botulinum toxin prevents the release of the acetylcholine neurotransmitter from a neuron into the gap between the neuron and muscle. Under normal circumstances, the released acetylcholine would interact with muscle-cell receptors on the other side of the gap, activating the muscle. In addition, evidence indicates botulinum toxin has the ability to lessen pain distinct from its spasticity-lowering effects. Specifically, botulinum toxin also appears to inhibit the release of substance P, a neurotransmitter, which, as discussed previously for capsaicin, is involved in transmitting pain signals.

A) In 2008, Dr. C. Marciniak and associates (USA) evaluated the use of botulinum toxin to treat spasticity and, as one of several secondary assessments, reduce pain (3). In this retrospective study, the charts of 28 individuals with SCI who had been treated with botulinum toxin for spasticity were reviewed. Patient age averaged 48 (range 20-76) years, and in 20, the cause of SCI was traumatic injury. Of the six individuals who had identified pain as an issue before treatment, five (83%) reported less pain afterwards. The investigators did not know whether this pain reduction was the result of less spasticity or due to botulinum toxin’s influence on pain transmitters, such as substance P.

3) Tetrahydrocannabinol (THC) is the active agent in cannabis, i.e., marijuana. Cannabis preparations have a long history of use for treating various neurological disorders and pain, including being used thousands of years ago as traditional Chinese and Indian (i.e., Ayurvedic) herbal remedies. THC binds to receptors on the surface of central-nervous-system cells. Research suggests that this binding affects the activity of GABA, which, as discussed before, is a key neurotransmitter involved in pain perception.

A) In a 2007 study, Dr. U. Hagenbach and colleagues (Switzerland) examined THC’s influence on primarily SCI spasticity (4). In addition, a number of secondary effects were also evaluated, including pain through self assessments. Twenty-five subjects with SCI were initially recruited for the various study arms. Of these, 11 and 14 had paraplegia and tetraplegia, respectively; all but two were men; and age ranged from 19 to 73. Of the 22 subjects treated with an oral THC preparation, 15 consumed the drug for six weeks. Although the results indicated an initial statistically significant reduction in pain, the effect did not persist over time.

SURGICAL APPROACHES

Dorsal Root Entry Zone Lesions

Spinal nerves project off the left and right side of the spinal cord to every part of the body through openings in the vertebral column. As shown below, these spinal nerves are composed of dorsal roots, which carry sensory information into the spinal cord, and ventral roots, which carry motor or movement information out of the spinal cord toward muscles. The location where the dorsal roots enter the spinal cord is called the dorsal root entry zone (DREZ).

Although specific mechanisms are still unclear, evidence suggests that the DREZ is a key area in transmitting or processing pain stimuli. Spinal cord injury or related neurological trauma, such as brachial plexus nerve-root avulsion (nerve roots stretched or torn away from the cord,) triggers aberrant activity within this pain-processing area. As such, surgical procedures were developed to destroy the DREZ tissue producing this dysfunctional activity. Basically with these procedures, after the spinal cord is exposed through a laminectomy, radiofrequency, laser, or other devices are used to produce a series of lesions in the DREZ tissue in the problematic area of the spinal cord.

Although these DREZ-lesioning procedures have had some success in reducing certain types of SCI-associated pain, they are not innocuous. Numerous complications have been observed, including, because nervous tissue is being destroyed in an inexact process, the further loss of sensation and function. As more function-restoring strategies have emerged in recent years, the tradeoff between not-guaranteed pain reduction versus the potential loss of additional function combined with the inability to access these emergent strategies has become more questionable.

The following summarizes key studies evaluating the pain-reducing effectiveness of DREZ lesioning.

1) The radiofrequency DREZ-lesioning procedure was initially described by Drs. Blaine Nashold and Roger Ostdahl (USA) in 1979 for pain caused by nerve-root avulsion. Using an electrode with a two-millimeter tip, about 10-20 radiofrequency-coagulation lesions spaced at 2-3-millimeter intervals were made in the DREZ area associated with the avulsed roots. These lesions gradually coalesced to produce a coagulation strip extending from the uppermost to lowermost intact root. Of the 18 patients with intractable pain due to brachial plexus avulsion injuries, 13 experienced good, lasting pain relief (i.e., 75+% pain relief). However, a number experienced mild to moderate lower extremity weakness on the same-side after the procedure.

2) Building upon their success described previously for brachial plexus avulsion injuries, in 1980, Drs. Blaine Nashold and Elizabeth Bullitt (USA) reported the results of using DREZ lesioning to reducing central pain in 13 individuals with lower-level spinal cord injuries. These injuries involved damage to the conus medullaris (the terminal end of the spinal cord) or cauda equina (a bundle of nerves occupying the vertebral column below the spinal cord). All subjects suffered from lower extremity pain starting several days to 12 years after injury. With age ranging from 35-60 years, five subjects were females and seven were males.

Using DREZ-lesioning procedures similar to those previously described, between seven and 16 lesions were made on each side of the cord, extending from one or two levels above the injury level down to the injury level or slightly below. Patients were followed from 5-38 months. All but two reported at least a 50% reduction in pain, with seven completely free of pain. Most patients were able to reduce their pain medications. Unfortunately, three patients lost significant function afterwards.

3) In 1984, Dr. Hans-Peter Richter and Klaus Seitz (Germany) reported the results of using DREZ-lesioning procedures to treat neuropathic pain in 10 patients (9 males, 1 female). Of these patients, eight had cervical injuries, mostly due to accidents, resulting in nerve-root avulsion, and two had thoracic injuries. Age ranged from 17-68 years. The DREZ-lesioning procedures were similar to those described above. Of the patients with cervical injuries, one died six days and another 36 days after surgery. The surviving patients were followed for 5-30 months. Of these, three were entirely pain free, one had residual pain, and two had no reduction in pain levels. In both patients with thoracic injuries, pain levels were the same as before the surgery.

4) Also in 1984, Drs. Madjid Samii and Jean Richard Moringlane (Germany) reported the results of treating 35 patients with DRES lesioning, including 22 with brachial plexus avulsion injuries and five with spinal cord injuries. Age ranged from 18-59 years; and 28 patients were male, and seven were female. The time period between pain onset and the DREZ-lesioning procedure ranged from three months to 35 years. Of the 22 patients with brachial plexus avulsion injuries, 17 had very good pain relief (defined as >70% reduction in pain), three had good pain relief (50-70% reduction in pain), and two had fair pain relief (<50% reduction in pain). Of the five patients with SCI, two, two, and one had very good, good, and fair pain relief, respectively. After the procedure, 18 patients suffered from transient sensory and/or motor deficits.

5) Due to the complications associated with radiofrequency DREZ-lesioning, Dr. Stephen Powers and associates (USA) used microsurgical lasers to produce more precise, smaller, and reproducible lesions. Of the 21 patients, seven with age ranging from 27-48 years had pain associated with paraplegia. Followed for periods ranging from 2-19 months, six of these seven patients with SCI reported greater than 50% pain relief. In the overall treatment group of 21 patients, transient and persistent sensory abnormalities were observed in seven individuals.

6) In 1986, Dr. Allan Friedman and colleagues (USA) summarized the results of using radiofrequency DREZ-lesioning to treat intractable pain in 56 individuals with SCI. Patient age ranged from 27-72 years, and all had suffered pain for at least eight months before surgery. Pain relief was considered 1) “good” if the patient was either free of pain or the pain did not require analgesics or compromise daily activities, 2) “fair” if the patient still needed non-narcotic analgesics, and 3) “poor” if residual pain required narcotic use or interfered with normal activities. Using these criteria, 50, 9, and 41% of the patients had good, fair, and poor pain relief, respectively, from the procedure. The investigators noted that certain types of SCI-pain syndromes responded better. For example, 74% of patients with pain below the level of injury had good pain relief. Complications were reported in 16 patients, including cerebrospinal fluid leaks and loss of function and sensation. For example, one patient who was able to walk with mechanical support before the procedure lost the ability afterwards.

7) In 1988, Dr. Stephen Powers et al (USA) summarized the results of treating 40 patients with various types of central pain with laser-generated DREZ lesions. Of these patients, 11 had paraplegia, nine from thoracic injuries and two from cauda-equina injuries. Patients were followed for periods ranging from four months to over five years. Five of the 11 individuals with paraplegia had good pain relief from the procedure; the others did not. Certain types of SCI pain appeared to be more responsive to DREZ lesioning, and those with thoracic injuries generally had better outcomes. Several individuals out of the 40 treated experienced motor and sensory abnormalities as a result of the procedure.

8) In 1990, Dr. Blaine Nashold and colleagues (USA) reported the results of treating 18 individuals with paraplegia, who had delayed pain associated with the development of a syringomyelia spinal cyst months to years after injury. Fourteen patients had a single cyst, and four had two. After surgically exposing the relevant area of the cord, restrictive adhesions were cut, the cyst opened and drained, and radiofrequency DREZ lesioning carried out. With follow-up averaging 3.5 years, pain relief was evaluated using the following criteria: 1) Good: no analgesics needed and no limitation of activities due to pain, 2) Fair: no narcotics needed and no limitation of activities due to pain, and 3) Poor: narcotics required and/or activities limited by pain. Using these criteria, 14 and four patients experienced good and fair pain relief, respectively.

9) In 1990, Dr. Ronald Young (USA) summarized his experience using DREZ lesioning to alleviate pain in 78 patients over a seven-year period. The pain was caused by a variety of disorders, including 20 with SCI and six with cauda-equina injuries. As technology evolved, three different DREZ-lesioning methods were employed. Initially, a radiofrequency method was used to treat 21 patients (group 1). Then a laser approach was employed to treat 20 individuals (group 2). Finally, a radiofrequency procedure using a smaller electrode was adopted for 37 patients (group 3).

Dr. Young noted strengths and weaknesses for the different procedures. For example, the initial radiofrequency method (i.e., group 1) had difficulty penetrating spinal-cord associated tissue due to the electrode’s larger tip size and produced lesions lacking consistency in size. These problems appeared to be minimized when the smaller electrode was later employed. The laser approach had a number of benefits, including 1) not having to actually touch the spinal cord, thereby avoiding physical trauma, and 2) creating closely spaced lesions. However, deficiencies were also noted. For example, small amounts of cerebrospinal fluid on the cord could significantly alter lesion size.

Of the 78 patients treated, 62% had satisfactory pain relief defined as at least a 50% reduction in pain, stopping of narcotic analgesic use, and better functional ability. Using these criteria, 55% on the individuals with SCI and 83% of those with cauda-equina injuries had pain relief. Comparing the three DREZ methods, 67, 45, and 68% of the group 1 (radiofrequency), 2 (laser), and 3 (radiofrequency – small tip), respectively, obtained effective pain relief. A variety of complications were observed, including a loss of function and sensation. Specifically, in group 1, 52% of the patients had complications; in group 2, 15%; and in group 3, 8%. This data indicated that the small-tipped, radiofrequency device produced the best results with the least complications.

10) In 1993, Dr. Robert Edgar and colleagues (USA) reported their experience using computer-assisted DREZ lesioning on 46 patients with central pain due to SCI. Noting that significant numbers of individuals failed to achieve adequate pain relief with traditional DREZ procedures, the investigators developed a computer-assisted process in which electrophysiological assessments were made in the DREZ at and above the injury area. After being computer analyzed, the electrophysiological activity associated with each specific location was categorized as normal or abnormal. Assuming that the areas of abnormal activity were associated with pain generation, DREZ-lesioning targeted these areas. In other words, areas of normal activity were left alone, which would minimize unneeded, potentially function-compromising neurological damage. Conversely, the area subjected to DREZ lesioning was expanded if abnormal activity was demonstrated to extend beyond the area that would have been normally targeted. Patients were followed for an average of 44 (range 2- 96) months. Using the computer-assisted process, 50-100% pain relief occurred in 92% of patients, and 100% pain relief occurred in 84% of the patients.

11) Reported in 1995, Dr. John Sampson and associates (USA) summarized the outcomes of DREZ-lesioning over a 14-year period for 39 individuals with intractable pain due to trauma of the conus medullaris or cauda equina. Thirty-one patients were males, and age ranged from 17-66 years. Patients were followed for an average of three years. Pain relief was classified as good if the patients required no pain-killing analgesics, fair if pain was significantly reduced but there was still a need for non-narcotic medication for pain that no longer interfered with daily-living activities, and poor if the previous criteria were not met. Using such classification, 54 and 20% of the patients had good and fair pain relief, respectively, from the procedure. About 20% of the patients had serious complications, including weakness, bladder and sexual dysfunction, cerebrospinal fluid weak, and wound infection.

12) In 1996, Dr. Stefan Rath and colleagues (Germany) reported the results of treating 51 patients with pain generated from variety of spinal and peripheral nerve lesions using the DREZ procedure. Of these patients, 22 (18 males and 4 females) had SCI. Their age ranged from 17-74 (average 47) years, and 20 had thoracic and two lumbar injuries. Patients had been injured by fall (10), traffic accidents (8), skiing (3), and gunshot (1). Seven patients also had syringomyelia cysts at the level of injury, which were drained in addition to the DREZ lesioning.

After the procedure, patients were followed for periods of time ranging from 10 months to 13 years, rating their postoperative pain levels as a percentage of preoperative levels. A greater than 75% reduction in pain was defined as good, a 25-75% reduction considered fair, and less than 25% reduction defined as poor. Using these classifications, 12 (55%) of the patients with SCI had good or fair continuing pain relief. Five of the seven individuals with syringomyelia cysts reported poor outcomes. After the procedure, several patients reported new paraesthesias (i.e., tingling, burning, numbness sensation of the skin).

13) In a 1997 paper, Dr. Rath’s team further summarized their experience using DREZ lesioning in now a total of 68 patients, including 23 with SCI. Results were similar to those reported previously, specifically, 12 patients noting continuous good or fair pain relief.

14) Reported in 1999, Dr. Milan Spaic et al (Yugoslavia) used DREZ lesioning to treat six males with SCI with neuropathic pain. Ages ranging from 25-35 years, all had sustained thoracic or lumbar level injuries (T10-L1) due to gunshot wounds. In a function-restoring effort, omental transposition had been performed on all six 4-17 months after injury. As discussed elsewhere, with this procedure, the omentum, a highly vascularized, nutrient-rich, fatty tissue covering the gut, is surgically tailored to create a tissue pedicle of sufficient length so it can be sutured over the spinal-cord injury site. For these patients, omental transposition did not improve function nor did it inhibit pain development.

Because of this failure, 30-60 months after omental transposition, the patients underwent DREZ-lesioning. In this surgery, the omentum was removed, DREZ-lesioning carried out, and the omental tissue reattached. Based on follow-up periods ranging from 7-12 months, four of the six patients had complete pain relief, and two had 80% pain relief, sufficient enough to eliminate pain medications. Some existing sensation was compromised by the DREZ surgery.

15) In 2001, Dr. Marc Sindou, a pioneer in developing the DREZ procedure, and colleagues (France) provided an analysis of the long-term results obtained by treating over a 19-year period 44 patients with neuropathic pain resulting from spinal cord or cauda equina injuries. Age averaging 46 years, 32 patients were males and 12 females. Injury was cause by road accidents (16), falls (11), industrial accidents (5), gunshot (4), skiing (2), and other (1). The level of injury was cervical in three patients, thoracic in 22, thoracic-lumbar in five, and lumbar in 14. Pain relief was considered good if the patient estimated at least a 75% reduction in pain, fair if a 25-75% reduction, and poor if a 25% or less reduction.

Three months after the DREZ surgery, 66, 20, and 14% of the patients reported good, fair, and poor pain relief, respectively. Thirty patients were followed for longer periods ranging from 1-20 (average 6) years. Of these, 60% reported good pain relief, 20% fair results, and 20% poor pain relief. The investigators noted that those individuals with lower level injuries and those with incomplete injuries appeared to get more enduring benefit. Few neurological side effects were noted.

16) In 2002, Dr. Scott Falci and associates (USA) reported their experience using an electrophysiological guidance system to improve DREZ-lesioning outcomes for central pain in 41 patients with SCI. Basically, this system was used to identify areas of electrical hyperactivity indicative of abnormal pain processing. Such identification would allow better targeting of the DREZ lesions. Patient age ranged from 19-72 (average 46) years, and 38 were men and three women. All patients had sustained either thoracic or thoracic/lumbar injuries and had started experiencing pain within a year of injury, most soon after injury. The average time lapsing between initiation of pain and surgery was 62 months.

The investigators concluded that the guidance system greatly improved outcomes. Using the system, 84% of the patients reported 100% pain relief. However, the majority experienced some loss of sensation in areas affected by the spinal-cord area being lesioned. In addition, the procedure resulted in new motor deficits in five patients.

17) Between 1986 and 2006, Dr. Yucel Kanpolat et al (Turkey) treated 55 patients with pain resulting from a variety of neurological causes, including 17 with SCI. Of these patients, 44 were men and 11 women with an average age of 46 (range 24-74) years. Two different DREZ surgical procedures were used. In 44 patients, the conventional DREZ-lesioning approach was employed, while in 11 patients, the DREZ surgery targeted a nearby spinal area called the nucleus caudalis. Patients were followed for periods ranging from six months to 20 years. One year after surgery, 69% of the conventionally treated patients and 62% of the alternatively treated patients reported satisfactory pain relief. A patient in each group died after surgery.

18) In 2011, Dr. F. Ruiz-Juretschke and associates (Spain) summarized the outcomes of treating 18 patients with DREZ-lesioning over a 15-year period. The most common disorder within this group was brachial plexus avulsion; only two had SCI. Seven patients were men and 11 women. Age ranged from 27-77 (average 52) years. The duration of pain before surgery averaged six years. Patients were followed for periods ranging from 6-108 (average 28) months. Subjectively evaluated by the patient, pain relief after DREZ lesioning was classified as excellent if pain was absent, good if pain relief exceeded 75%, moderate if it was between 25-75%, and poor if it was less than 25%. Using this classification, long-term pain relief was deemed excellent in three patients, good in six, moderate in three, and poor in six. After surgery, 67% of the patients could reduce their pain medications, and 28% were able to go back to work. The best results were observed in patients with brachial plexus avulsion. The investigators reported neurological complications in four patients.

OTHER PAIN-MANAGEMENT TECHNIQUES

Acupuncture

As discussed elsewhere, acupuncture has considerable therapeutic relevance for SCI, including even restoring some function after injury. In addition, the therapy can influence pain-processing neural pathways and neurotransmitter systems. For example, it stimulates muscle sensory nerves, which send messages to the spinal cord, midbrain, and pituitary, which, in turn, releases pain-reducing molecules such as endorphins and cortisol-producing hormones. It has been shown in rabbits that the effects of acupuncture-induced analgesia can be transferred to other rabbits through the transfer of cerebrospinal fluid.

Because acupuncture has been extensively used in the general population to treat pain from a variety of causes, several studies have been initiated to evaluate its ability to reduce SCI-associated pain:

1) In 2001, Dr. Sangeetha Nayak and associates (USA) reported the results of treating 22 individuals with SCI for pain. Age averaged 43 years, and 68% of the participants were men. The time since injury and duration of pain both averaged ~8.5 years. Cause of injury included motor vehicle accidents (10), sporting accidents (5), gunshot or stabbing (4), falls (2), and other (1). Eight, 13, and 1 had cervical, thoracic and lumbar/sacral injuries respectively.

All subjects had 15 acupuncture sessions over a 7.5-week period. In each session, 6 to 14 acupuncture points were needled. Certain points were always needled, including a key point located in the Governor acupuncture meridian between the C-7 and T-1 vertebrae (see figure). Other points were selected based on locations of pain reported by subjects, as well as their response to previous sessions.

Subjects rated their pain intensity using a 0-10 pain scale in which 0 corresponded to no pain and 10 to pain as bad as it can get. To be eligible for the study, all subjects had to have a 5+ pain level for at least six months before enrollment. At various times before and after treatment, subjects were asked to rate their present pain, average pain for the past two weeks, and worst pain experienced during the preceding two weeks.

Secondary assessments focused on 1) pain-associated general health issues, such as sleeping, appetite, range of motion, etc. 2) the degree to which pain interfered with daily activities of life, 3) mood changes, such as depression or anxiety, 4) perceived psychological well being, and 5) treatment expectations.

Using the 0-10 pain scale, average pain decreased from 6.9 before to 5.4 after treatment, a reduction which persisted for some time. More specifically, 18% of the subjects reported a significant reduction in pain (defined as at least a 3-point decrease in pain levels), 27% reported a moderate reduction (2-3-point decline), 36% reported minimal pain relief (< 2-point decline), and 18% reported an increase in pain.

Those who responded better to acupuncture tended to have pain located above the injury, an incomplete injury, or musculoskeletal, as opposed to, central pain. Subject expectation of pain relief that would accrue did not correlate with the pain relief they actually got; i.e., believing in acupuncture’s potential did not result in more benefit.

Regarding secondary assessments, there was a reduction in various pain-associated symptoms (e.g., sleep difficulties) and less interference in activities of daily living. No improvements in anxiety or depression were noted. Improvement in psychological well being, especially in perceived vitality/energy levels, was documented.

2) As reported in 2003, Dr. Linda Rapson and colleagues (Canada) developed an electro-acupuncture protocol to treat SCI-associated neuropathic pain. Under this protocol, acupuncture needles were inserted in three points of the Governor Meridian (points 18, 20, 21; see illustration) in the scalp midline and in a fourth point called the Yin Tang located between the eyebrows. After insertion, the needles were electrically stimulated for 30 minutes. Patients were initially treated five times per week, and treatment was continued until full relief of pain was accomplished or no further benefits accrued.

The investigators retrospectively reviewed the medical charts of 36 patients with spinal cord dysfunction (22 with traumatic injuries) who were treated for pain using this electro-acupuncture protocol over a five-year period. Twenty-three and 13 were men and women, respectively, and age ranged from 17 to 75 years. Of the 36 patients identified, 24 benefited from treatment, including 18 who experienced pain relief after only one treatment. No adverse side effects were observed

3) In 2001, Dr. Trevor Dyson-Hudson and colleagues (USA) evaluated the use of either acupuncture or Trager bodywork (below) to treat shoulder pain in individuals with SCI who used a manual wheelchair. This investigation was initiated by studies suggesting that as many as 68% of those with SCI have such pain due to pushing a wheelchair, transfers, and various activities of daily living. Fourteen men and four women were recruited with age averaging 45 (range 28-69) years. On average, they had been injured ~15 years and had shoulder pain for ~6 years. Cause of injury was motor vehicle crashes (9), falls (3), gunshot (2), diving accidents (1), and surgical/medical complications (4). Subjects reported doing about 10 wheelchair transfers per day.

Subjects were randomized to receive either 10 acupuncture or Trager treatment sessions over a five-week period. In each acupuncture session, various points associated with upper extremity pain and areas of tenderness were needled. In the Trager sessions, gentle motions were used to loosen joints, ease movement, and release chronic pain patterns. The subjects were also taught Mentastic exercises (from “mental gymnastics”) to help recognize movements or tension patterns that may lead to pain.

Various assessments of pain were recorded periodically before, during, and after treatment, including the “The Wheelchair User’s Shoulder Pain Index” (WUSPI). With this index, subjects were asked to report shoulder pain intensity for 15 activities of daily living (e.g., transfers, etc) using a 0 (no pain) to 10 pain (worst possible pain) scale for each activity. The scores for all 15 activities were combined into a single score (150 being the highest possible score).

By the end of the treatment period, WUSPI pain levels had decreased ~54% for both the acupuncture- and Trager-treated individuals. Although pain started trending upwards after treatment was discontinued for the acupuncture subjects, it continued to decline somewhat for Trager subjects. The investigators speculate that this continued decline was due to the Trager emphasis on movement reeducation, which would have a lasting influence even after treatment was stopped. Overall, 89% and 100% of the acupuncture- and Trager-treated individuals, respectively, reported less shoulder pain after treatment.

4) Because the previous study did not have a placebo-control group, the investigators initiated a somewhat similar investigation in 17 subjects with shoulder pain who were randomized to receive either active or sham acupuncture, which needled supposedly inactive, nearby skin areas. In this more rigorously designed, double-blind study, neither the subject nor the evaluator knew who received active versus sham treatment. Of the 17 subjects, two were females and 15 males; 6 and 11 had tetraplegia and paraplegia, respectively; age averaged ~39 years; and the time lapsing since injury averaged ~11 years.

Subjects received 10 treatments over a five-week period. For the acupuncture-treated subjects, six points in the vicinity of the shoulder pain and two points further away were needled. Also needled were points of tenderness that did not correspond to classical acupuncture points. The needles were manually stimulated several times (e.g., twirling) and left in for 20 minutes. In the case of the sham subjects, needles were inserted in supposedly inactive areas somewhat near the true acupuncture points. Also, the needles in the sham-control subjects were more shallowly inserted and not manipulated.

Once again, the primary measure of pain was “The Wheelchair User’s Shoulder Pain Index,” which was assessed before, right after, and five weeks after treatment. Using this index, shoulder pain in acupuncture-treated subjects decreased 66% compared to 43% for the sham-treated individuals.

In the case of the more general 0 (no pain) to 10 pain (worst pain possible) scale, shoulder pain in acupuncture-treated individuals decreased from 5.0 to 2.5 after treatment, and in the sham subjects declined from 4.3 to 3.6 after treatment. Seventy-five percent of the individuals in the acupuncture group reported a clinically meaningful reduction in pain (defined as a 30% reduction) five weeks after treatment compared with only 25% for the sham-treated individuals.

Although active acupuncture resulted in a greater reduction in pain compared to sham treatment, due to the relatively small sample sizes, the differences between the two groups were not statistically significant. As discussed by the investigators, the use of sham acupuncture points in clinical trials has been problematic because they are not neutral controls. Although not as effective as true acupuncture points, sham points also evoke physiological responses through different mechanisms and, therefore, are questionable as a control comparison.

5) In 2011, Drs. Cecilia Norrbrink and Thomas Lundeberg (Sweden) reported the results of treating 30 individuals with SCI and neuropathic pain for six weeks with either twice-weekly acupuncture or massage therapy (15 in each group). The acupuncture group was composed of 12 men and 3 women with an average age of 47. The time since injury averaged ~12 years, and five had tetraplegia. The massage group had relatively similar composition.

In each session 13-15 acupuncture points were needled, including several points that were stimulated by electro-acupuncture. The investigators used a variety of pain assessments involving a 0 (no pain) to100 (worst possible pain) scale. A clinically meaningful reduction in pain was defined as a decrease of 18 units on this 0-100 pain scale. Using this scale, subjects periodically rated their present, general, and worst pain intensity, as well as pain unpleasantness and other measures.

Ratings for general pain, present pain, and pain unpleasantness all had a statistically significant decline at the end of acupuncture treatment. Specifically, general pain decreased from 63 to 48 after treatment, present pain decreased from 59 to 40, and pain unpleasantness decreased from 70 to 47. Although declines were also observed for the massage group, they were not as large and did not reach statistical significance.

Hypnosis

“The trick is not minding that it hurts” – Peter O’Toole in Lawrence of Arabia

Hypnosis is a trance-like state of consciousness distinguished by increased susceptibility to suggestion, relaxation, and imagination. Based on evidence that it can significantly alter the perception of pain, Dr. Mark Jensen and colleagues (USA) have examined its potential to reduce the unique pain associated with SCI (1-6). If effective, hypnosis would avoid the many adverse side effects associated with pharmaceutical or surgical approaches.

As in all life, our perception molds our reality. For example, a long wait in an express-checkout lane can be viewed as either a pain-in-the-behind hassle or an opportunity to read a tabloid magazine on display. Likewise, if you get slammed playing wheelchair rugby, you’ll probably forget your headache for awhile. The attention you direct to the pain is energy that fuels it. Basically, the goal of hypnosis is to cut off this fuel-line of consciousness by placing the pain within a different context, deemphasizing your focus on it, or directing your attention elsewhere.

1) In 2000, Dr. Jensen and colleague Dr. Joseph Barber reported the results of treating four individuals with SCI with four sessions of hypnosis. Before treatment, participants were evaluated for 1) their responsiveness to hypnosis, 2) pain intensity using a 0-10 pain scale with 0 corresponding to no pain and 10 corresponding to the most intense pain imaginable, and 3) the degree to which pain interfered with their sleep using another 0-10 scale in which 0 corresponded to no disturbance and 10 to unable to sleep. Participants also kept daily diaries assessing pain and sleep interference for the previous day. They were encouraged to practice self hypnosis daily between treatments and afterwards using a 20-minute audiotape prepared during the first session.

After hypnotic induction, participants were given various suggestions for pain relief, examples of which are shown below. Future sessions were tailored based on patient responsiveness to the suggestions in the initial session. At the end of each session, patients were told that they would be able to recreate their hypnotic state by taking and holding a deep breath and listening to the audiotape specifically tailored for them.

EXAMPLES OF HYPNOTIC SUGGESTIONS

1) Direct suggestions for decreased pain	Example: “You notice that as you relax, as you feel more comfortable, you feel less and less pain, almost as if the pain were going away, or getting smaller.”
2) Direct suggestions for increased comfort	Example: “You can feel more and more comfortable…”
3) Replacement of pain with other sensations	Example: “You can notice how any feelings of pain or discomfort can change…to other feelings… feelings that are not unpleasant…that are more comfortable…like warmth or a very pleasant tingling sensation…”
4) Ability to ignore pain	Example: “As your pain continues to decrease, as you build this barrier between pain and your experience, it is almost like it is muffled…you notice it less and less.”
5) Displacement	Example: “The pain and discomfort that you usually experience can now be directed and moved to a different part of the body.”
6) Hypnoanaesthesia	Example: “It is now time to anaesthetize the site of your pain. Notice how naturally, how easily the area of pain and discomfort is being engulfed in a psychological anaesthesia.”

Patient experiences are summarized below:

Patient 1, a 65-year-old woman who sustained an incomplete C-5 cervical injury 43 years earlier, had foot pain that would build up during the day to a level of 6.5 on the aforementioned 0-10 pain scale. This interfered with her ability to sleep. She was rated a 3 out of a possible 5 in terms of hypnotic susceptibility. Her pain levels dropped to 3.8 during the five days after her final session. Likewise, her sleep-interference rating dropped from 6.2 to 3.4 during the same period. Because she did not continue to practice self hypnosis, her pain intensity and sleep disturbance returned to pretreatment levels when assessed at two months and one year after treatment.

Patient 2, a 28-year-old male who sustained a complete C-5 injury 10 years earlier due to a motor vehicle accident, had stinging pain in his legs and hands. His hypnotic responsiveness was rated 5 out of 5. His pain intensity decreased on average from 2.0 before treatment to 1.5 afterwards, and sleep interference decreased from 3.0 to 1.0. After treatment, he practiced self hypnosis daily using the prepared audiotape. Decreases in pain levels and sleep interference were maintained at two months and one year after the initial treatment.

Patient 3, a 37-year-old male who sustained a C-4/5 level injury due to gunshot 14 years earlier, had lower back pain rated as 5 in intensity on the 0-10 pain scale. His hypnotic susceptibility was 5 out of 5. Treatment and daily self hypnosis reduced his pain to 0.5 and eliminated sleep interference. However, pain intensity and sleep interference started to increase four months after treatment because he stopped his daily practice after losing his audiotape.

Patient 4 was a 42-year-old woman who had been injured at the T12/L1 level 17 years earlier due to a fall. She experienced constant and uncomfortable electrical sensations in her legs, which she rated as a 4.5 on the 0-10 pain scale. Her hypnotic susceptibility was 4 out of 5. With treatment and self-hypnosis practice, her pain intensity dropped to 2.0, and her sleep interference decreased from 3.5 to 1.5. Although before treatment, she was always aware of her pain, afterwards there were periods in which she was completely unaware of it.

From this preliminary data, the investigators concluded that hypnosis has the potential to reduce pain and improve sleep quality in varying degrees for some individuals with SCI. All patients reported decreases in pain and sleep disturbance after treatment. Those who practiced self hypnosis maintained or even improved on these treatment gains.

2) In 2005, Dr. Jensen and colleagues reported the results of using hypnosis to treat pain in 33 individuals with SCI (13), multiple sclerosis (10), amputation (7), and other disabilities (3). Participant age averaged 51(range 28-79) years, and 18 were women and 15 were men. The treatment consisted of 10 hypnosis sessions spaced at time intervals ranging from daily to weekly sessions depending upon individual availability.

In each session, one of five pain-relieving suggestions was given after hypnotic induction, involving 1) decreased pain, 2) deep relaxation, 3) hypnotic analgesia, 4) decreased unpleasantness, or 5) sensory substitution. After the initial suggestion, participants would be returned to a fully alert state and then after another hypnotic induction, be provided the next suggestion. The process was repeated until all five suggestions had been administered. Unlike the previous study in which later sessions were tailored based on the responsiveness to the suggestions in the initial sessions, all sessions incorporated every suggestion. Although tailoring appears more effective, this procedure was adopted to standardize the intervention for the sake of better comparing study results. At the end of each session, participants were given posthypnotic suggestions to facilitate self-hypnosis practice and to promote extended pain-relief benefits.

The study’s primary outcome measure was average pain intensity, using the aforementioned 0-10 pain scale. This was assessed before treatment, after the 10 sessions were completed, and three months later. The 27 individuals who completed all ten sessions reported an average 21% reduction in pain. Of these 27 participants, 10 reported a clinically meaningful, 30% or greater reduction in pain. Much of the pain reduction still existed three months after treatment. Although it was difficult to make meaningful conclusions given limited sample sizes for each disability, participants with amputation seemed to have the greatest pain relief. Specifically, they reported a 43% average reduction in pain compared to 17% for SCI and 10% for multiple sclerosis.

3) Building upon this study, in 2008, Dr. Jensen’s investigative team summarized the long-term, pain-relief benefits accruing to 26 individuals with pain, now including 12 with SCI, 8 with MS, 5 with amputation, and 1 with post-polio syndrome. Average age was 50 (range 28-79) years, and 14 of the 26 participants were men. As described above, each individual had been treated with 10 hypnosis sessions. To maintain pain-amelioration benefits over time, participants were encouraged to regularly practice self-hypnosis by using a post-hypnotic cue given at treatment and, in some cases, a practice tape provided at the 3- or 6-month follow-up assessment.

Using the 0-10 scale, pain levels were assessed 3, 6, 9, and 12 months after treatment. At all follow-up periods, average pain intensity was lower than that observed before initial treatment. The percentage of participants reporting a clinically significant (i.e., >30%) reduction in average pain intensity at these follow-up times were 27%, 19%, 19%, and 23%, respectively. Although these reductions seem modest, the majority of participants reported that they frequently used self-hypnosis, on average 16-17 days per month. Apparently, even though pain intensity for the whole day may have improved only slightly, substantial short-term pain relief lasting several hours occurred. These results indicated that self-hypnosis might be especially useful for pain flare-ups.

4) In 2009, Dr. Jensen and associates reported the results of treating a 27-year-old male Army Sergeant who had sustained a cervical C6, ASIA-B (see appendix) incomplete injury from a gunshot to his neck. Because of severe pain in his arms, he could not tolerate range-of-motion and physical-therapy exercises. During such exercises, he rated this pain as 10 (worst pain imaginable) on the 0-10 pain scale.

Because the patient experienced adverse reactions to pain medications, hypnosis was tried. Over a five-week period, he had 10 hypnosis sessions lasting 45-75 minutes each. At the beginning of each session, he was asked about his current pain location, average pain intensity over the past day, and current pain intensity. During the first two sessions, the patient was given five specific pain-reduction suggestions, involving direct pain reduction, relaxation, imagined anesthesia, decreased pain unpleasantness, and replacement of pain with other sensations. Future sessions were tailored based on his responsiveness to these suggestions. In addition, suggestions were given concerning his overall healing, progression in therapies, and increased self-confidence about his eventual discharge from the hospital and return to civilian life. Each session ended with post-hypnotic suggestions for continued self-hypnosis practice. To facilitate his practice, audio recordings were prepared for his use.

Due to hypnosis treatment, the patient’s pain levels greatly decreased. As a result, he could straighten his fingers (which was previously not possible due to intense pain), and his hands lost their “claw-like” appearance. Furthermore, he could now participate more fully in therapies with less pain and was able to substantially reduce pain medications. At the end of each session, his pain levels were never greater than 2 on the 0-10 scale. At a six-month telephone follow-up, the patient reported that his sensitivity to pain had decreased considerably. At its worst, it was a 5-6 and at best, a 1.5-2 on this scale. He had continued to practice the self-hypnosis skills learned during treatment.

5) In 2009, Dr. Jensen et al summarized their treatment of 37 individuals with SCI possessing chronic pain. These individuals were randomized to be treated with either hypnosis or a biofeedback-relaxation technique. The study was designed to distinguish hypnosis’ true pain-relieving ability from any placebo effect. Unlike studies evaluating drug efficacy in which an inactive agent can be readily used for comparison, it is difficult to create a control for treatment modalities such as hypnosis in which subjects will most likely know if they are being treated and, in turn, report benefits skewed by that knowledge.

Because of this difficulty, the investigators chose to select biofeedback relaxation as a control treatment because, in part, it could be administered in a fashion somewhat similar to hypnosis. In hindsight, they concluded that it was a poor choice because it was not inactive but rather a modality that brought some pain relief through mechanisms overlapping with those of hypnosis (e.g., suggestive techniques). In other words, both the hypnosis and control treatments brought about some pain relief, making definitive conclusions on effectiveness more difficult.

Participant age averaged 49.5 (range 19-70) years, and, 28 were men. Of the 37 initially recruited and randomized to the two treatment groups, 28 completed the 10-treatment regimen. Similar to the procedures described earlier, in the initial hypnosis sessions, participants were given five specific pain-reduction suggestions, involving decreased pain, deep relaxation, hypnotic anesthesia, decreased unpleasantness, and sensory substitution. In turn, future sessions were tailored based on individual responsiveness to these specific suggestions. Participants were encouraged to practice self hypnosis between sessions, as well as after completion of the 10 sessions by using post-hypnotic suggestions and through listening to audiotapes recorded at the sessions. To make the hypnosis and control study arms more comparable, a biofeedback audiotape, which included a relaxation exercise, was also provided to the control subjects.

Average daily pain intensity was evaluated before and after treatment and three months later. In addition, current pain intensity was measured before and after each treatment session. Although the reduction in pain intensity before and after each session was comparable for both hypnosis- and biofeedback-treated individuals, hypnosis subjects experienced a greater reduction in average daily pain intensity. Specifically, their average daily pain decreased from 6.10 on the 0-10 pain scale before treatment to 5.05 afterwards to 4.93 three months later. For the biofeedback group, average daily pain decreased from 3.38 before treatment to 3.17 afterwards but increased to 3.78 three months later. Three months after treatment, 31% of the hypnosis subjects and 22% of the biofeedback subjects reported a clinically meaningful 30% or greater decrease in their average daily pain relative to pretreatment levels.

Interestingly, participants experiencing neuropathic pain had greater pain reduction from hypnosis than those with nonneuropathic pain (e.g., visceral, mechanical spine, or overuse).

Transcutaneous Electrical Nerve Stimulation (TENS)

Transcutaneous electrical nerve stimulation (TENS) has been extensively used to treat pain generated from a variety of causes, including neuropathic origins. Basically, TENS devices transmit low-voltage, electrical impulses at various frequencies through electrodes attached to the skin in areas associated with pain. Although numerous studies document the pain-relieving benefits accruing by using TENS devices, because few studies were controlled, experts continue to debate the true efficacy of the procedure.

Evidence suggests that TENS may lessen pain through a variety of physiological mechanisms, including 1) inhibiting the transmission of pain signals from the peripheral nervous system into the spinal cord, and 2) increasing the levels or influence of pain-reducing, neurotransmitters, such as opioid-like endorphins.

Over the years, several studies have focused on the potential of TENS to treat SCI-associated pain, including the following:

1) In 1975, Drs. Ross Davis and Richard Lentini (USA) briefly summarized the preliminary results of using TENS to treat 31 subjects with various forms of SCI-associated pain. Subject age varied from 23 to 68 years, and injury levels ranged from the cervical C-3/4 to lumbar L-5 level. Some pain relief was reported by 13 of the 31 subjects, those with central pain accruing less benefit.

2) In 1978, Dr. H.J. Hachen (Switzerland) reported the results of treating 39 individuals with SCI suffering from chronic intractable pain. Twenty-five were men, and 14 were women; 32 and 7 had paraplegia and tetraplegia, respectively; and 18 and 21 had sustained complete and incomplete injuries, respectively. The duration of pain had ranged from 6 to 35 months. In the first week of treatment, TENS stimulation was applied for six consecutive hours, and thereafter, the treatment schedule was tailored to individual requirements. After a week of treatment, 49% of the subjects reported almost complete and 41% slight pain relief. After three months, these figures were 28% and 49%, respectively.

3) In 2009, Dr. Cecilia Norrbrink (Sweden) reported the results of treating 24 subjects with SCI and neuropathic pain with either high- or low-frequency TENS. Subjects included 20 men and four women with an average age of 47 (range 29-68) years. The time lapsing since injury varied from 0.5 to 28 (average ~7) years. Thirteen, eight and three had cervical, thoracic, and lumbar injuries, respectively.

Subjects were assigned to be treated with either high- or low-frequency TENS for two weeks. After a two-week washout period in which no treatment was administered, treatment was reversed; i.e., the subjects who had received high-frequency TENS now were given low-frequency treatment for two weeks and vice versa. After being shown how to use the TENS device, subjects were instructed to employ it at home three times a day, 30-40 minutes per session for two-weeks. The device’s four electrodes were place adjacent to the spinal column in the area of injury.

Figure 1. Study design. HF = high-frequency, LF = low-frequency, TENS = transcutaneous electrical nerve stimulation

Various scales, questionnaires, and other measurement were used to assess pain and various factors affected by pain, such as mood, sleep quality, and life satisfaction. For most assessments, no statistically significant benefit accrued from TENS treatment, and no difference could be discerned between high- and low-frequency approaches. However, using the global pain-relief scale, in which subjects rated treatment as having no effect, insufficient effect, rather good effect, good effect, or very good effect, 29% and 38% of the subjects reported some benefit using high-frequency and low-frequency stimulation, respectively. In addition, in follow-up interviews, subjects reported increased relaxation, decreased use of pain killers, increased ability to work, improved mobility in shoulder joints, and improved sleep. After the study concluded, 25% of the subjects requested a prescription for a TENS device so they could continue treatment.

Healing Touch

As discussed elsewhere, healing touch is “an energy therapy in which practitioners consciously use their hands in a heart-centered and intentional way to support and facilitate physical, emotional, mental, and spiritual health.” It’s often used with other therapies to accelerate healing.

Funded by the US Veterans Administration, Dr. Diane Wardell and colleagues (USA) carried out a pilot study evaluating the use of Healing Touch to treat SCI-associated neuropathic pain. Seven male veterans with SCI, at least six-months post injury, were treated with healing touch and compared with five who received a non-healing-touch intervention. All subjects had more than one month of neuropathic pain at a level greater than 5 on a scale ranging from 0 (no pain) to 10 (worst possible).

Certified haling touch practitioners administered once-a-week sessions to each subject for six weeks. To avoid practitioner variability, each subject was treated by the same healer throughout the study. Based on the practitioner’s assessment of the subject’s energy fields, the sessions were individualized; i.e., different techniques were used on different individuals. At the end of the study, the primary caregiver (e.g., wife) for each subject was given the option to be trained in healing touch so treatment could be continued.

In addition to a variety of before-and-after quantitative measurements of pain and other factors, qualitative opinions were solicited from the subjects. Although the study was inherently limited due to the small number of subjects and sessions, the results suggested that healing touch “may be beneficial in the areas of coping, pain management, decreasing fatigue, decreasing confusion, increasing life satisfaction, and decreasing depression.” The investigators believed the results warranted further, more definitive studies.

Qualitative reactions from participants included:

	Carl felt that his pain “medication really kicked in” but did not attribute it to healing touch.
	Nick experienced “almost no pain – it’s amazing. I feel like a whole new person.”
	Sam could not discern any effect other than “feeling heat on one of my hands,” which is where he experienced most of his pain.”
	Mike had an initial response of “decreased spasms” and “moved my mind to a state of silence.”
	Charles noted that the pain “was practically gone. It is unbelievable.”
	Mark felt that the treatment was relaxing but did not notice any other effects. His caregiver noticed improvement
	Bruce had a “little bit” of response.

Vitamin-D Supplementation

The importance of vitamin-D to individuals with SCI has been discussed elsewhere. In addition, vitamin-D-deficient individuals tend to have more chronic pain, which may be alleviated by vitamin-D supplementation (1-10). Although understandings are still evolving, evidence indicates that vitamin D regulates the synthesis of key immune-system molecules (called cytokines) implicated in pain-associated inflammatory responses.

It is uncertain how much supplementation can lessen the unique pain experienced by individuals with SCI. For example, it may help in overuse-related shoulder pain but have little impact on neuropathic pain. We do not know. Nevertheless, vitamin-D is a nothing-to-lose-potentially-much-to-gain approach that, at minimum, will enhance overall health.

Vitamin-D levels can be measured through a simple blood test, which measures blood levels of a specific vitamin-D derivative called 25-hydroxvitamin D. Levels above 30 nanograms (one billionth of a gram) per milliliter are considered sufficient, between 20-29 ng/ml insufficient, and < 20 ng/ml inadequate.

Using these criteria, it’s estimated that one billion people worldwide lack health-optimizing vitamin-D levels. At special risk are the elderly and individuals with dark skin pigmentation, especially those who live in cloudy, northern latitudes. Wintertime sunlight possesses little of the wavelengths needed to produce vitamin D in much of the northern U.S.

Scientists speculate that people with physical disability are more likely to have compromised vitamin-D levels because the disability limits time outside in the sun. In the case of SCI, one study indicated that individuals with chronic SCI were twice as likely to have deficient vitamin-D levels compared to able-bodied individuals. Levels apparently go down quickly after injury as demonstrated in another study showing deficient vitamin-D levels in 93% of patients admitted to acute, inpatient rehabilitation, including 21% who were considered severely deficient with levels <10 ng/ml.

Numerous studies suggest that vitamin-D deficiency has a key role in pain manifestation, including the following:

1) Dr. Vasant Hirani (UK) looked at the relationship of pain and vitamin-D levels in 2,000+ adults aged 65 and over living in England, a northern, cloudy country. Overall, as we age we become less efficient in synthesizing vitamin D and converting it to its physiologically active form. Hirani’s study indicated that moderate to extreme pain was present in 53% of these elderly individuals and was correlated with poor vitamin-D status.

2) Dr. Wei Huang and collaborators (USA) evaluated the effects of vitamin-D supplementation in 28 veterans with chronic pain and low vitamin-D levels. Age averaged 46 years, 18 were men, and 20 were African Americans, reflecting this group’s tendency to possess suboptimal vitamin-D levels. The average vitamin-D level was a deficient 18.6 ng/ml. After receiving vitamin-D supplementation for three months, the average level increased to 26 ng/ml.

Subjects rated their pain before and after supplementation using a 0 to 10 pain scale, in which 0 corresponded to no pain and 10 as worst possible pain. In addition, a quality-of-life questionnaire was administered which asked about physical functioning, the extent health interferes with work, bodily pain, general health, vitality, social functioning, the degree emotional problems interfere with work, and mental health. Finally, another questionnaire was used to assess sleep quality, which is frequently compromised by pain.

Using the 0-10 scale, average pain levels decreased from 7.1 to 5.7 after supplementation. Overall, subjects reported fewer areas of pain and a decreased use of pain medications. In addition, the results indicated an improvement in most of the quality-of-life components listed above, including the pain component. Finally, sleep improved after supplementation, e.g., subjects took less time to get to sleep and slept longer. The investigators concluded that “vitamin-D supplementation in veterans with multiple areas of chronic pain can be effective in alleviating their pain and improving sleep, and various aspects of quality of life.”

3) Individuals with SCI often experience neuropathic pain due to neural-tissue damage. Although studies focused on using vitamin-D to lessen neuropathic pain are limited, Drs. Paul Lee and Roger Chen (Australia) examined vitamin-D’s potential to relieve pain in 51 vitamin-D-deficient patients with diabetes. Common in individuals with SCI, diabetes frequently causes pain-generating, peripheral nerve damage. Three months of supplementation increased vitamin-D levels in subjects from an average of 18 to an average of 30 ng/ml. Several measures of pain were assessed before and after supplementation, including a 0 (no pain) to 5 (excruciating pain) scale. Using this scale, pain levels decreased from 3.3 before supplementation to 1.7 afterwards, a 48% reduction.

Emotional Freedom Technique

The Emotional Freedom Technique (EFT) is a form of acupressure-assisted exposure therapy, where you tap on various acupressure points while focusing on pain-associated emotional issues. Basically, the technique catalyzes the release of negatively charged, stuck emotions.

EFT has successfully treated issues that have yielded reluctantly, at best, to years of psychotherapy or medication. Furthermore, because virtually all chronic disorders have mind-body correlates, EFT has the potential to lessen physical symptoms and pain, and pave the path to healing. EFT is a self-healing and -empowerment technique that people can learn to do by and for themselves. It has no negative side effects.

EFT is based on two key energy-medicine tenets. First, we have an acupunctural system of points and meridians that regulate the flow of life-force energy throughout our bodies. As an analogy, view the meridians as a pipeline through which the energy flows, the acupuncture points as periodically placed, flow-controlling valves, and the acupuncture needles as the socket wrench that opens the valves. [With EFT, instead of needles, the pressure of tapping fingers regulates the flow.] Overall, each of us has a unique energy flow that is optimal for our health, and when this flow gets off-kilter for any mind-body-spirit reason, we become compromised. Acupunctural theory believes that pain is often a symptom of stuck energy.

Secondly, emotions are a function of our internal energy flows. When our energy flows are weak or blocked, we may feel tired, cranky, irritable or easily triggered. When our energy flows are strong and open, we feel more fresh, present, alive, loving, and joyful. By crimping energy flow and distribution, negative emotions become psychosomatic baggage. Although we may not appreciate the influence of these, often pushed-down, emotions in everyday life, they are there, gnawing away at our ability to function optimally. EFT releases the energy behind these emotions. The heavy emotional suitcase we have been dragging through the long concourse of life becomes a light carry-on of non-charged memories.

Overall, EFT-generated benefits include 1) desensitizing negative emotions and associated physical reactions; 2) releasing mood-altering neurotransmitters and hormones; 3) triggering the relaxation response; 4) interrupting stuck or limiting behavioral patterns/mind-sets; 5) resetting the body’s internal electrical system; 6) initiating energetic, perceptual, cognitive, and physical shifts; and 7) inducing feelings of joy, satisfaction, relaxation, peacefulness, and well-being.

EFT can blunt the impact of many of life’s “slings and arrows of outrageous fortune” that chip away at our spirit, ranging from the minor to the all-consuming. So to speak, EFT is the lint brush that wipes away the unneeded clumps of emotional lint that cling to us and cumulatively drag us down over time.

The suffering, anguish, or anxiety associated with major issues, like addiction, intense phobias, childhood abuse, trauma, or post-traumatic stress, often let up in response to EFT. On occasion, deep-seated, life-compromising issues have been quickly resolved with EFT. The emotional balloon swollen with negative charge is punctured and deflated.

Procedures: Given their often profound results, the basic EFT procedures are amazingly simple and can readily be picked up after a few short demonstrations. The use of EFT to specifically relieve pain is summarized in the book Freedom at your Fingertips compiled by Ron Ball (2006). Another good starting point is the website www.eftuniverse.com, which lists many resources, training opportunities, and practitioners.

As summarized in the Table, you tap on key acupuncture points while focusing on a specific issue. These points are specifically selected because they are located at the end of various acupuncture meridians. If you have limited finger mobility, use your hands or just visualize the tapping.

BASIC EFT PROCEDURES

Preliminary

1) Start by picking the issue, attempting to be as specific as possible. For general, amorphous issues, dissect them into component parts and work on each separately.

2) Assess issue intensity on a scale from zero to 10 (most intense).

3) Create a reminder phase to repeat while tapping. For example, if you have nagging shoulder pain, your reminder phrase might be just “shoulder pain.”

4) Locate the EFT “tender spot” by going to the base of the neck where a tie is knotted, and then go down three inches and over three inches. This area is sometimes tender when rubbed because of lymphatic congestion.

5) While rubbing the tender spot, state the following, for example, affirmation three times “Even though I have this throbbing pain in my right shoulder, I deeply and completely accept myself.”

Tapping Sequence

Using several fingertips, tap 7-10 times at each of the indicated locations (see illustration) while repeating your reminder phase. The tapping points proceed down the body, making them easier to memorize.

Face and Body: 1) Beginning of eyebrow on each side of nose, 2) Side of eyes, 3) Under each eye, 4) Under the nose, 5) Middle of chin, 6) Beginning of collarbone where the sternum and first rib meets, 7) Four inches under each arm, and 8) One inch below each nipple.

Hands & Fingers: Tap the 1) outside cuticle edge of your thumb at the base of the thumbnail, 2) thumb-facing edge of each finger (except ring finger) at fingernail base, and 3) the fleshy outside edge of the palm used to deliver a karate chop (To save time, tapping can be consolidated, e.g., the outside edge of your right thumb can be used to tap on the outside edge of your left thumb, etc.)

A longer EFT version includes tapping on the hand’s gamut point (see illustration) while carrying out various eye movements, counting, and humming tunes. Although sounding strange, different parts of the brain are stimulated with each of these actions.

Finally, reassess the intensity of the issue again and repeat the cycle.

Exercise

Studies suggest that exercise can reduce not only SCI-associated shoulder pain but perhaps neuropathic pain:

1) In 1999, Dr. K.A. Curtis’s investigative team (USA) examined the impact of a six-month exercise program on shoulder pain in 42 wheelchair users, including 35 individuals with SCI. Of the 42, 35 were men, age averaged 35 years, and the average duration of wheelchair use was 14 years. All subjects with SCI had injuries at the cervical C6 level or lower. Subjects were equally randomized into treatment and control groups. The treatment group received instruction in five shoulder exercises, which were performed daily at home for six months. Two of the exercises involved stretching and three focused on resistive strengthening.

Shoulder pain was assessed using the “Wheelchair User’s Shoulder Pain Index” (WUSPI). With this index, subjects reported the amount of shoulder pain associated with 15 activities of daily living (e.g., transfers, etc.). Each activity was assessed using a 1 (no pain) to 10 (worst pain ever experienced) scale. The scores for all activities were combined, giving an aggregate score ranging from 0-150.

Using this index, subjects completing the exercise program reported a 40% reduction in pain compared with 2% for the controls. In spite of the overall reduction, pain levels initially increased somewhat before declining as the exercise program was continued. Overall, the investigators concluded that the “findings supported the effectiveness of this exercise protocol in decreasing the intensity of shoulder pain which interferes with functional activity in wheelchair users.”

2) In 2003, Dr A.L. Hicks and colleagues (Canada) evaluated the impact of a long-term exercise program on strength and a variety of other factors, including pain, on individuals with SCI. Thirty-four individuals with traumatic SCI at the cervical C4 level or below were recruited for the study. Age ranged from 19 to 65 years, and the time since injury varied from one to 24 years. Eighteen and 16 subjects has tetraplegia and paraplegia, respectively.

Of the 34 subjects, 21 were randomized into an exercise program and 13 into a control group. Subjects in the exercise group participated in a nine-month, twice weekly exercise program that involved both arm ergometry and resistance training with free weights or weight machines. In contrast, control subjects were offered a bimonthly education session on topics including exercise physiology, osteoporosis, and relaxation techniques.

Before and after the exercise program, subjects rated how much pain they experienced and how it interfered with normal work over the preceding four weeks using a six-point scale in which 1 represented “none/not at all” and 6 “very severe/extremely.” By the end of the nine-month study period, the exercisers reported a modest reduction in pain while the controls reported an increase.

3) In 2006, Dr. Deborah A. Nawoczenki and colleagues (USA) evaluated the potential benefits of an eight-week strengthening and stretching exercise program on existing shoulder pain in 21 manual wheelchair users with mostly SCI. These individuals were compared to 20 asymptomatic controls. Of those in the intervention group, age averaged 21 years, 15 were men, and the time since injury averaged 17 years. Thirteen and eight had incomplete and complete injuries, respectively.

The eight-week home exercise program consisted of stretching and strengthening exercises with elastic band resistance, focusing on specific muscles associated with shoulder pain. The controls received no intervention. The primary pain assessment was the previously discussed Wheelchair User’s Shoulder Pain Index. Using this index, shoulder pain was significantly reduced after completion of the exercise program.

4) In 2007, Dr. Mark Nash and colleagues (USA) examined the effects of a circuit resistance exercise training on muscle strength, endurance, anaerobic power, and shoulder pain in seven men with paraplegia. Age ranged from 39 to 58 years, the time since injury averaged 13 years, and the injury level varied from the thoracic T5 to T12 level. The exercise program consisted of training three times weekly for 16 weeks with resistance (weight lifting) and endurance (arm cranking) training. Using the previously described Wheelchair User’s Shoulder Pain Index, shoulder pain decreased on average from 32 before the program was started to 5 at the end of the study.

5) In 2011, Dr. Sara J Mulroy et al (USA) evaluated the effectiveness of an exercise program on shoulder pain in 80 manual wheelchair users with SCI. Average age was 45, and 71% were men. Average time since injury and duration of shoulder pain was 20 and 5.5 years, respectively. Half of the recruited subjects were randomized to a 12-week home-based program of shoulder strengthening and stretching exercises together with strategies on how to optimize transfers, raises, and wheelchair propulsion. The other half were assigned to control group, which saw an instructional video reviewing shoulder anatomy, mechanisms of injury, and general concepts in managing shoulder pain.

Shoulder pain was assessed before and after the intervention using the Wheelchair User’s Shoulder Pain Index. Using this scale, pain levels decreased in the exercisers from 51 to 15 after finishing the program, a decline that persisted four weeks later. In contrast, no change was noted in the controls.

6) In a 2012 study, Dr. C. Norbrink and associates (Sweden) evaluated the effects of an exercise program on both musculoskeletal and neuropathic pain in eight individuals with SCI. Of these eight individuals, six were males, age varied from 30-67 (average 50) years, and the time lapsing since injury ranged from 7-29 (average 18) years. Seven and six subjects had neuropathic and musculoskeletal pain, respectively (four had both). One patient also had visceral pain. The level of injury ranged from the thoracic T5 to lumbar level L1 level. The exercise program used a double-poling ergometer adapted for persons with lower extremity impairments. Subjects trained on this device for 50 minutes three times a week for 10 weeks.

Before and after the exercise program, pain was evaluated using a variety of assessments, including the 0-10 pain scale extensively discussed elsewhere. For the seven subjects with neuropathic pain, the average pain level decreased from 5 to 3; and two reported much improvement, two minimal improvement, and three no change. For those individuals with musculoskeletal pain, average pain intensity declined from 4 at baseline to 0 at study end. All but one had no musculoskeletal pain at the end of the study, and the number of days per week with pain declined from an average of 5.5 to 0.7 days.

Five of the eight subjects had reported shoulder pain at the beginning of the study. In these individuals, shoulder pain was also measured before and after the program using the Wheelchair User’s Shoulder Pain Index. Using this 0-150 assessment, shoulder pain decreased from an average of 37 to 18 after the program was completed.

The investigators noted that the impact of the exercise program on neuropathic pain appears to be comparable to many of the pharmaceutical drugs studied for treating neuropathic pain. They concluded “Despite the lack of studies on exercise as a treatment for SCI neuropathic pain, we recommend health-care staff to consider prescribing regular physical training for this group as it is a safe treatment option with many more advantages than just pain relief.”

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