The last few decades have witnessed increasing sophistication and advances in the rehabilitation of spinal cord injured (SCI) patients with marked improvements in the quality of care accompanied by significant reductions in morbidity and mortality. Despite these impressive gains in bladder, skin, cardiovascular and respiratory care, the treatment of chronic pain in SCI has proven largely refractory to medical management. This lack of treatment efficacy has been complicated by an incomplete understanding of pain in individuals with spinal cord injuries and lack of a standardized framework upon which to classify these injuries (Burchiel and Hsu 2001).
Pain is a frequent complication of traumatic spinal cord injury. Reported estimates of the incidence of pain following SCI range anywhere from 11 to 94% (Botterell 1953, Burke 1973, Davidoff 1987, Davis 1947, Donovan 1982, Kaplan 1962, Kennedy 1946, Munro 1948, 1950, Nashold 1981) with more recent studies reporting an incidence from 48-94% (Davidoff et al. 1987, Cohen et al. 1988, Rose et al. 1988, Britell and Mariano 1991, Mariano 1992, Cairns et al. 1996). Estimates of debilitating or disabling pain range from 11-34% (Botterell 1953, Davis 1947, Kaplan 1962, Munro 1948, Nepomunceno 1979). Bonica (1991) noted that on combining the data on 6 reported studies of pain in SCI and 1,028 subjects (Botterell 1953, Burke 1973, Davis 1947, Nepomunceno 1979, Rose 1988, Woolsey 1986), 53% had various types of “deafferent” pain. These wide ranging estimates are felt to be a reflection of significant heterogeneity in defining pain in this population.
Bonica (1991) reviewed data contained in 10 reports that surveyed 2,449 SCI patients (Botterell 1953, Britell 1986, Burke 1973, Davis 1947, Kaplan 1962, Munro 1950, Nepomunceno 1979, Richards 1980, Rose 1988, Woolsey 1986). Chronic pain was present in 1,695 (69%) and in 30% of these patients it was rated as severe. Six of the reports (Botterell 1953, Burke 1973, Davis 1957, Nepomunceno 1979, Rose 1988, Woolsey 1986) analyzed the different types of pain. Out of a total of 1,965 patients, 608 (31%) of the patients had central pain/dysesthesia/phantom limb pain, 219 (12%) had root pain, and 198 (10%) had visceral pain caused by a central mechanism. There were 1,028 (53%) SCI patients with deafferentation pain.
It is estimated that 30-40% of patients with SCI experience severe disabling pain (burke and Woodward 1976). Pain is often reported as the most important factor for decreased quality of life. Nepomuceno (1979) noted that 23% of individuals with cervical or high thoracic SCI and 37% of those with low thoracic or lumbosacral injury would trade the loss of sexual and/or bowel and bladder function as well as hypothetical possibility for cure to obtain pain relief.
Rose et al. (1988) sent a questionnaire to 1,091 spinal cord injured individuals. “Suitable” replies were received from 885 subjects with a total of 615 reporting pain at or below the level of the injury. In 110 subjects this occurred in a nerve root distribution with the remainder below the neurological level of SCI. Pain, which was reported as constant in 43%, was considered severe at some point in the day in half the sample and mild to moderate in 21% of respondents. Prior to the SCI, 595 of the sample were employed; afterwards only 325 were employed. Interestingly 98 SCI individuals (11%) reported it was the severity of their pain and not their paralysis, which stopped them from working. 269 of the 325 SCI subjects (83%) who were employed reported that the pain interfered with their work. A total of 118 SCI subjects found that the pain was severe enough to stop social activity. Pain appeared to be more severe in the evening and at night, interfering with sleep in 325 of respondents (37%). This study clearly pointed out the importance of chronic pain in determining disability and morbidity in SCI patients (Rose 1988).
Persons with SCI who complain of severe pain are more likely to have low spinal cord or cauda equina lesions (Ragnarsson 1997, Davis and Martin 1947, Botterell et al. 1953, Nepomuceno et al. 1979). Severe pain was noted in 10-15% of persons with quadriplegia; 25% of those with thoracic paraplegia and 42-51% of those with lesions of the cauda equina (Ragnarsson 1997)
One study examining the timing of the development of pain post-SCI noted that in 901 patients with SCI, pain started immediately after SCI in 34%, within the first year in 58%, pain increased over time in 47% and decreased over time in 7%. (Turner et al 2001). Turner et al. (2001) noted that pain most often started within the first 6 months following SCI. This has also been noted in several other studies (Turner and Cardenas 1999, Stormer et al.1997, Nepomuceno et al. 1979, Siddall et al. 1999).
Widerstrom-Noga et al. (2001) conducted a careful analysis of the relationship between the location of the pain and the patients’ description of the pain. In this study 217 of 330 patients reporting chronic pain in a previous survey agreed to participate in the study. Participants had been injured for an average of 8.2 ± 5.1 years and 55.4% were quadriplegic. Most subjects in this study marked multiple areas on a pain drawing with the back area being most frequently implicated (61.8%). 59.9% complained of a burning pain while 54.9% described an aching pain. Interestingly burning pain was significantly associated with pain localized to the front of the torso and genitals, buttocks and lower extremities. In contrast, aching type pain was significantly associated with pain localized to the neck, shoulders and back.
Widerstrom-Noga et al. (2001) noted that the descriptor “burning” is often associated with neuropathic pain (Siddall et al. 1999, Ragnarsson 1997, Fenollosa et al. 1993) whereas “aching” is often associated with musculoskeletal pain (Siddall et al. 1999, Tunks 1986). However, since there is a significant overlap in the quality of pain types it is difficult to establish a definitive clinical relationship(Eide 1998, Bowsher 1996, Widerstrom-Noga et al. 2001). The authors then go on to suggest that musculoskeletal-type pain (best characterized by the aching pain in the neck, shoulders and back) is potentially amenable to therapeutic interventions and aggressive attempts should be made to ameliorate this type of pain. All of this underscores the need for a reproducible classification system of the pain experienced following SCI. Bennett et al (2007) have noted that the increasing reliance on validated screening tools may help “form the basis of forthcoming clinical diagnostic criteria”.
Siddall et al. (1997) noted that one of the concerns regarding SCI-related pain was a lack of consensus over a classification system for SCI pain. This has led to considerable variation in incidence and prevalence rates for pain post SCI depending on the classification system used. Twenty-eight (28) classification schemes have been published between 1947 and 2000. A Task Force on Pain Following Spinal Cord Injury of the International Association for the Study of Pain has introduced a taxonomy, which classified SCI pain based on presumed etiology (Burchiel and Hsu 2001, Siddall 2000).
Table: Proposed IASP Classification of Pain Related to SCI (Burchiel & Hsu 2001)
Table: SCI pain types according to major classification
Table: Reliability of SCI pain classification systems
A new International Classification of Spinal Cord Injury Pain (ICSCIP) has been proposed. This new classification aims to be more comprehensive in the types of pain directly related to or commonly found in individuals with SCI.
Musculoskeletal or mechanical pain occurs at or above the level of the lesion and is due to changes in bone, tendons or joints (Guttmann 1973). This is referred to as nociceptive pain caused by a variety of noxious stimuli to normally innervated parts of the body (Ragnarsson 1997). Overuse of remaining functional muscles after spinal cord injury or those recruited for unaccustomed activity may be of primary importance in some patients (Farkash 1986). Pain may also be secondary to spinal osteoporosis or facet arthropathy (Farkash 1986). Instability of the vertebral column may also be a problem (Farkash 1986). Pain is usually dull and aching in character and although more common soon after SCI, it may become chronic.
Sie et al. (1992) studied 239 SCI outpatients for the presence of upper extremity pain. Of the 136 patients with quadriplegia, 55% reported upper extremity pain, most commonly at the shoulder (46% of all subjects). In the case of shoulder pain, 45% were orthopedic-related including tendonitis, bursitis, capsulitis and osteoarthritis. Of the 103 paraplegics, 66 reported upper extremity pain with two-thirds reporting symptoms of carpal tunnel syndrome and 13 reporting musculoskeletal-related shoulder pain. Daylan et al (1999), in a questionnaire returned by 130 SCI patients, found that 58.5% of patients reported upper extremity pain. Of these, 71% had shoulder pain, 53% wrist pain, 43% hand pain, and 35% elbow pain. Pain was most likely to be associated with pressure relief, transfers, and wheelchair mobility. Subbarao et al (1995), in a survey of 800 SCI patients, found that 72.7% of responders reported some degree of chronic pain at the wrist and shoulder, with wheelchair propulsion and transfers being responsible for most of the pain. McCasland et al (2006) noted that in their survey, 70% of SCI had shoulder pain, one-third had a previous injury to their shoulder and 52% reported a bilateral pain. Quadriplegics were more likely to have shoulder pain (80%). Previous shoulder trauma increased the risk of having shoulder pain.
"Central" dysesthesia or "deafferentation" pain is the most common type of pain experienced below the level of SCI and is generally characterized as a burning, aching and/or tingling sensation. In many cases this dysesthetic or deafferentation pain has defied a pathophysiological explanation (Britell, 1991) although most researchers firmly support a central nervous system origin for this pain. Nashold (1991) goes as far as stating that except for radicular pain, all other pains of paraplegia are central or deafferentation in origin. This pain is most often perceived in a generalized manner below the level of the lesion, often a diffuse burning type of pain (Britell 1991, Tunks 1986). Burning pain is reportedly most common with lesions at the lumbar levels, although it may be found with SCI at thoracic and cervical levels (Tunks 1986). Nashold (1991) reported this pain occurred almost immediately after SCI and persisted.
Beric (1997) refers to this pain as central dysesthetic pain (CDP) and found dissociative sensory loss and absence of spinothalamic-anterolateral functions, with different degrees of dorsal column function preservation present almost exclusively in incomplete SCI patients. CDP takes weeks or months to appear and is often associated with recovery of some spinal cord function. Paradoxically CDS is often characterized by complete loss of temperature, pinprick, and pain perception below the level of the lesion. It rarely occurs in spinal cord Injuries with complete sensory loss or loss of both sensory and motor functions below the level of the lesion. Davidoff et al. (1987a) concurred and further noted dysesthetic pain was more likely to be found in incomplete paraplegia resulting from penetrating wounds of the spinal cord, and in spinal fractures treated with conservative management.
A number of factors may contribute to exacerbations of these "central" pain syndromes; these include visceral diseases or disturbances, movement, smoking or alcohol, emotional factors, fatigue, and even weather changes (Botterell 1953, Davis 1947, Davis 1975, Tunks 1986). Pressure sores, particularly if infected, or an occult injury such as a fracture, may result in an increase in burning, dysesthetic pain. These stimuli often provoke autonomic dysreflexic-like symptoms and simultaneously also may aggravate this "burning" pain.
Individuals with SCI frequently experience a band of pain and hyperalgesia at the border zone between diminished or abnormal and preserved sensation (Tunks 1986, Botterell 1953, Davis 1975, Heliporn 1978, Kaplan 1962, Maury 1978, Melzack 1978, Michaelis 1970). In the more recent literature, this segmental pain is further described as occurring at or just above the level of sensory loss in the cutaneous transition zone from the area of impaired/lost sensation to areas of normal sensation, involving at least one to three dermatomes (Friedman 1989, Nashold 1991, Ragnarsson 1997) and is often associated with spontaneous painful tingling or burning sensations in the same area. Ragnarsson (1997) also noted that in an individual with a cervical cord injury, segmental pain may be described as tingling, burning or numbing pain in the shoulders, arms or hands, those with a thoracic cord injury frequently describe a circumferential, feeling of tightness and pain around the chest and abdomen while lumbar lesions tend to be localized to the groins and different parts of the lower extremities. According to Nashold (1991) paraplegics often complain that touching the skin in the pain region activates the pain causing it to radiate into the lower parts of the body, especially the legs. Pain can be triggered by stroking and/or touching the skin in adjacent painful dermatomes (Nashold 1991). Even light touch or the pressure of clothing or bed sheets over this region may provoke marked discomfort (Tunks 1986). It may be accompanied by sweating or vasodilation at or below the level of hyperalgesia. Segmental pain is generally symmetrical although a partial spinal cord injury with asymmetrical neurological involvement will produce asymmetries (Nashold 1991).
This pain has also been described as "neuropathic at level pain" (Siddall et al 1997) Although several theories have been proposed (Tunks 1986, Nashold 1981, Pollock 1951, Matthews 1972, Levitt 1983, Melzack 1978) the neurological mechanism responsible for this area of hyperalgesia after spinal injury is not well understood (Farkesh 1986). Although radicular pain is most severe in incomplete SCI lesions, it is also seen in transected cauda equina lesions which are by definition radicular types of pain (Heaton 1965, Siddall et al. 1997). It may also be secondary to spinal cord instability by facet or disc material, or to direct damage to the nerve root during the initial injury (Burke 1973, Nashold 1991). This “radicular” pain is associated with sensory change in the involved painful dermatome (Nashold 1991) and is most common to cervical or lumbosacral nerve roots. Non-neural structures, such as the dura mater, have also been suggested as a source of radicular pain (Cyriax 1969, Farkash 1986). In addition, it has been suggested that central borderzone pain may be generated in the damaged spinal cord just proximal to the spinal cord injury (Nashold 1991, Pollock 1951). Unfortunately, unless there is definitive evidence on imaging of nerve root damage, it is difficult to distinguish between these various mechanisms of pain.
To reflect this uncertainty Siddall et al. (1997) in their proposed classification of SCI pain note that this "neuropathic at level pain" is divided into radicular and central pain. Radicular pain is due to nerve root pathology while central pain is due to changes within the spinal cord or possibly supraspinal structures. Pain attributable to nerve root damage is suggested by features of neuropathic pain (i.e. burning, stabbing, shooting, electric-like pain, allodynia) and increased pain with spinal movement. Sjolund (2002) notes that this pain is thought to occur from nerve root entrapment and may occasionally benefit from decompression.
However, pain, which appears radicular in nature, may occur in the absence of nerve root damage. This leads to the second grouping of borderzone pain, namely central pain or that which is due to pathology within the spinal cord thought to be the result of damage to the gray matter of the dorsal horn of the spinal cord (Ragnassaron 1997, Woolsey 1995). According to Ragnassaron (1997), such an injury “has been said to result in hyperactivity of the nociceptor cells within the dorsal horn (Nashold and Bullitt 1981, Nashold and Ostdahl 1979)which can be electrically recorded (Nashold and Alexander 1989).” Sojlund(2002) notes that this second type of at level neuropathic pain is experienced as a girdle pain uni- or bilaterally in 2-4 segments of the transitional region. This pain is described as stimulus independent, often accompanied by troublesome allodynia or hyperalgesia and thought to arise from segmental deafferentation (Sjolund 2002).
Most studies of chronic SCI pain have focused on the medical causes and clinical manifestations of pain while much less is understood about how psychosocial factors impact SCI pain (Summers 1991). A negative psychosocial environment along with increased age, depression, anxiety and intellect were found to be associated with reports of greater post-SCI pain severity interfering with activities of daily living (Richards et al. 1980). Greater pain severity was not associated with physiological factors such as injury level, completeness of injury, surgical fusion and/or instrumentation or veteran status. The authors were unable to distinguish whether the psychological factors were a consequence of, or contributors to, greater pain severity. Summers et al (1991) studied 54 SCI patients (19 with quadriplegia and 35 with paraplegia) and of these, 42 patients assessed with the Pain questionnaire found that anger and negative cognitions were associated with greater pain severity. Severity of pain was higher in patients who reported pain in response to a question on general well being , those that were less accepting of their disability and those that perceived that a significant other would express punishing responses to their pain behaviours. Pain itself was found to be associated with greater emotional distress than the SCI itself. The authors concluded that the experience of pain was associated with psychosocial factors. Hence treatment of post-SCI pain should involve these multidimensional aspects.
Cohen et al. (1988) found that patients with complete SCIs reported significantly less severe pain than did pain clinic patients. However, they did not differ from patients with incomplete lesions. Patients with complete SCIs and pain clinic patients showed a significantly more disturbed MMPI (Minnesota Multiphasic Personality Inventory)profile than did patients with incomplete SCIs. It was hypothesized that those patients with complete lesions view themselves as more functionally limited than patients with incomplete lesions, and the completeness of the SCI may be more important in determining psychosocial adjustment than pain per se. Rintala (1998) in community-based men with SCI found that chronic pain was associated with more depressive symptoms, more perceived stress and poorer self-assessed health.
Woollaars et al (2007) administered questionnaires to persons with a SCI. Of the potential 575 subjects, 49% provided responses. SCI pain prevalence was 77%. Factors associated with less pain intensity included more internal pain control and coping, less catastrophizing, a higher level of lesion and a non-traumatic SCI cause. More pain was associated with greater pain-related disability. Lower catastrophizing was related to better health. Factors related to greater well-being included less helplessness and catastrophizing, greater SCI acceptance and lower anger levels. Greater levels of depression were associated with higher levels of SCI helplessness, catastrophizing and anger. The authors noted that chronic SCI pain and quality of life were both largely associated with several psychological factors of which pain catastrophizing and SCI helplessness were more important. Surprisingly, pain intensity showed no independent relationships with health, well-being and depression.
Widerström-Noga et al (2007) studied 190 patients with SCI and chronic pain and were able to identify 3 subgroups. The first group was described as ‘dysfunctional’, characterized by higher pain severity, life interference, affective distress scores, and lower levels of life control and activities scores. The second group was described as ‘interpersonally supported’, characterized by moderately high pain severity, and higher life control, support from significant other, distracting responses, solicitous response, and activities scores. The final group was described as ‘adaptive copers’, characterized by lower pain severity, life interference, affective distress , support from significant others, distracting responses, solicitous responses, activities and higher life control scores. Compared with dysfunctional subgroup, the interpersonally supported group reported significantly greater social support.
When pain post SCI is refractory to pharmacological and surgical treatment, it is important to fully understand the negative impact of the patient’s psychosocial environment prior to undertaking more invasive approaches to treatment.
Table: Catastrophizing and Pain Post SCI
Giardino et al (2003)noted that pain-related catastrophizing, or exaggerating the negative consequences of a situation has been associated with greater pain intensity, emotional distress and functional disability in patients with chronic pain conditions and SCI. This was thought to provide partial support for a “communal coping” model of catastrophizing, where catastrophizing in persons with pain may function as a social communication directed toward obtaining social proximity, support or assistance.
Before moving to pharmacological and surgical interventions, it is important to deal with those factors which may intensify or worsen the experience of pain. As mentioned previously, SCI pain may be worsened by decubitus ulcers, a urinary tract infection or stone, autonomic dysreflexia, increased spasticity, anxiety, depression, psychosocial factors and other contributors to post-SCI pain (Davis 1998, Tunks 1986). There are a number of non-pharmacological interventions for post-SCI pain which have been studied from massage to hypnosis.
Massage and heat are used primarily to treat musculoskeletal pain. Their benefit is well known in a number of musculoskeletal pain disorders, although there are significant differences among therapists as to how treatment is delivered.
Table: Massage and Heat in Post-SCI Pain
It stands to reason that local heat and massage therapy would be most effective for musculoskeletal pain post-SCI.Budh and Lundeberg (2004)in a survey of SCI patients 3 years post-injury found massage and heat were the best non-pharmacological treatments. No prospective studies examining heat and massage as treatment modalities for post-SCI pain have conducted.
Acupuncture is a component of traditional Chinese medicine that has been used for the treatment of pain for thousands of years and is based on the premise that illness arises from the imbalance of energy flow (Qi) through the body (Dyson-Hudson et al. 2001). Needle acupuncture involves inserting fine needles into specific points to correct these imbalances (Pomeran 1998; NIH Consensus 1998; Wong & Rapson 1999; Dyson-Hudson et al. 2001). Acupuncture has been shown to activate type II and type III muscle afferent nerves or A delta fibers, blocking the pain gate by stimulating large sensory neurons as well as releasing endogenous opioids, neurotransmitters and neurohormones (Pomeran 1998; Wong & Rapson 1999; Dyson-Hudson et al. 2001).
Table: Acupuncture in Post-SCI Pain
Dyson-Hudson and colleagues conducted two RCTs (2001; 2007) examining the effect of a 10 treatment, 5 week program of manually stimulated acupuncture on shoulder pain compared to two different control interventions. In the first study, Dyson-Hudson et al. (2001),compared acupuncture treatment to Trager Psychosocial Integration performed by a certified Trager practitioner. Trager therapy is a form of bodywork and movement re-education designed to induce relaxation and encourage the patient to identify and correct painful patterns. It was hypothesized that chronically contracted muscles shortened by stress led to pain (Dyson-Hudson et al. 2001). There was a significant effect over time for both treatments in reducing shoulder pain but there was no difference between the two groups. The second RCT, (Dyson-Hudson et al. 2007) examined acupuncture against sham acupuncture (i.e. minimal depth needle insertion at nonspecific anatomic sites). The results suggested that acupuncture was no more effective than sham acupuncture for the treatment of shoulder pain post SCI and/or that there may be a significant placebo effect associated with these interventions.
Nayak et al. (2001)administered 15 acupuncture treatments over a 7.5-week period of time. Pain intensity decreased from pre-treatment to post-treatment with post-treatment decline in pain intensity being maintained at 3 month follow-up. Despite these results, 54.5% of those treated reported a worsening of pain after treatment.Those that reported pain below their injury did not respond to treatment (p<.05). Those who reported pain relief at 3 month follow-up reported only moderate levels of pain intensity at the beginning of the study compared to those who did not report pain relief at follow-up (p<.01). With the overall reduction in pain intensity there were also a decrease in pain interference with ADLs and an improvement in overall well being. The authors felt that 50% of patients demonstrated improvement in their pain with acupuncture.
Rapson et al. (2003)asked patients to rate their pain intensity according to a visual analogue scale after electroacupuncture treatments. Sixty-seven percent (24/36) of patients reported improvement, with improvement best for those with bilateral symmetric constant burning pain.
Banerjee (1974) reported on five patients who developed burning, distressing pain below the level of SCI and who responded to transcutaneous electrical nerve stimulation (TENS) strong enough to lead to muscle contraction below the level of injury. The exact mechanism of action for this analgesic response was not delineated.
Exercise has been shown to improve subjective well-being for individuals with chronic disease and disability.
Table: Exercises for Post-SCI Pain
Ginis et al. (2003) studied SCI patients who underwent a regular exercise program and compared them to SCI patients who did not. Those who underwent the regular exercise program experienced a significant improvement in pain scores which in turn accounted for improved depression scores. Ditor et al. (2003) found that pain scores were negatively correlated with adherence to a later exercise program.
Shoulder pain is a common form of musculoskeletal pain following SCI and is often the result of increased physical demands, awkward or over-use of the upper extremities as the individual with SCI compensates for loss of lower limb functioning (Curtis et al, 1999). Curtis et al. (1999) has noted, “tightness of the anterior shoulder musculature, combined with weakness of the posterior shoulder musculature both seem to contribute to development of shoulder pain in wheelchair users (Curtis et al 1999, Burnham et al. 1993, Powers et al. 1994, Millikan et al. 1991)and may be further complicated by paralysis and spasticity in the individual with tetraplegia (Silverskiold and Waters 1991, Powers et al. 1994)”. The prevalence of shoulder pain in SCI individuals ranges between 30-100% (Curtis et al. 1999) and is a consequence of increased physical demands and overuse (Pentland and Twomey 1991, 1994, Nichols et al. 1979).
Table: Shoulder Pain Management Post SCI
Curtis et al. (1999) in a RCT studied the effectiveness of a 6-month exercise protocol on shoulder pain experienced by wheelchair users where 42 patients were randomized into a treatment and a control group. Over 75% of all subjects reported a history of shoulder pain since beginning wheelchair use and 50% in both groups had current shoulder pain at the start of the study. The treatment group performed two exercises designed to stretch the anterior shoulder musculature and 3 exercises for strengthening the posterior shoulder musculature. Compliance rates were higher-over 83% of the subjects completed the 6-month protocol. Subjects in the treatment group decreased their average PC-WUSPI score by an average of 39.9% vs. only 2.5% in the control group. Despite this very significant change, 48.3% decreased in the paraplegic group and 27.2% in the tetraplegic group, the treatment group still had a higher mean score than the control group at the end of the study because of disparate baseline scores.
Nawoczenski et al. (2006) in a prospective controlled trial, found 21 SCI patients who participated in an ‘at-home’ exercise program experienced significant improvement in their WUSPI scores and on the Shoulder Rating Questionnaire (SRQ), when compared to subjects who did not participate in the exercise program. Exercises were designed to strengthen and stretch specific scapular and rotator cuff muscles. The authors concluded the exercises were effective at reducing pain and improving function.
In a pre-post study, Nash et al. (2007) reported that strength and anaerobic power of the upper extremities increased following 16 weeks of circuit training, while shoulder pain scores decreased significantly (p=0.008).
Finley and Rogers (2007) studied 17 patients including 9 SCI patients with a special wheelchair (MAGIC wheels 2-gear wheelchair). They found use of this particular chair reduced shoulder pain.
Hypnosis has been used to reduce pain in a number of painful clinical conditions as well as experimental pain (Jensen et al 2000). Hypnosis is appealing as a potential treatment because it is nonpharmacological although its use is controversial given the variability in hypnotic responsiveness.
Table: Hypnotic Suggestion and Post-SCI Pain
Jensen et al. (2000), in a before and after study, examined the impact of hypnosis on pain post-SCI. Eighty-six percent (86%) of the SCI patients reported a decrease in pain intensity and unpleasantness after hypnosis. There was no control group.
Cognitive behavioural therapy (CBT) is a commonly used psychological intervention for chronic pain. Often used as a part of a more comprehensive pain management program, it attempts to modify beliefs and coping skills, particularly when these beliefs and coping skills are dysfunctional.
Table: Cognitive Behavioural Therapy
Norribrink-Budh et al. (2006) treated post-SCI pain patients with a pain management program consisting of education, behavioural therapy, relaxation therapy, exercises, and body awareness training. This pre-post design study found no change in pain intensities or treatments with this approach.
In a prospective controlled trial, Perry et al. (2010) placed SCI individuals with chronic pain into either a multidisciplinary cognitive behavioural pain management program involving pharmacological and CBT treatment or in an usual care control group. The study found significant improvement in both the MPI and SF-12 MCS scores in the treatment group compared to the control group post treatment. A trend towards improved pain intensity and HADS score was also seen in the treatment group post treatment; however, scores returned to pre-treatment scores by 9 month follow-up.
Visual imagery therapy is a cognitive technique which uses guided images to alter perceptions and modify behaviour. It has been used in various studies to alleviate pain responses by changing feelings of perceived discomfort (Kazdin 2001; Korn 2002; Kwekkeboom 2001). It is based on a cortical model of pathological pain (Harris, 1999). This model states that the injury causes a mismatch between motor output and sensory feedback which in turn contributes to the pain. Studies have found normalization of the cortical proprioception representation results in recovery from pain (Floor, 2000; Maihofner et al. 2004; Pleger et al. 2005).
Moseley (2007) reported on five individuals with both a T12-L3 paraplegia (AIS B) and neuropathic pain who engaged in a virtual activity, where they were led through a guided walking exercise, visualizing that they were walking pain free. Of the four subjects who completed the trial (one patient withdrew from the study earlier due to distress), there was a mean 42 mm reduction in neuropathic pain following individual treatments, and 53 and 42 mm reductions immediately and 3 months following virtual walking daily for 3 weeks based on a 100 mm visual analog scale. Control treatments were visual imagery alone, and watching a movie, both of which resulted in less dramatic pain reduction; however, no statistical comparisons were done
Transcranial Electrical Stimulation (TCES) treatment involves applying electrodes to an individual’s scalp to allow electrical current to be applied and presumably stimulate the underlying cerebrum (Tan et al. 2006).
Table: Transcranial Electrical Stimulation Post-SCI Pain
Despite the fact that TCES is a relatively new treatment for post-SCI pain, 3 RCTs (Tan et al. 2006; Fregni et al. 2006; Capel et al. 2003) have been published, all suggesting it may be useful in reducing SCI-related chronic pain. Each of these investigations employed a sham stimulation control condition, using modified equipment. Although patients in all 3 studies reported some pain relief following treatment, there was no comment on how long the treatments should continue or how often they should be used.
Tan et al. (2006) conducted a double-blind RCT with 38 SCI participants with either chronic musculoskeletal or neuropathic pain receiving either active transcranial electrical stimulation (TCES) or inactive TCES (sham control) over 21 days. The electrical stimulation was set at a subthreshold level ensuring that patients were blind to their treatment group. The study found that SCI patients receiving transcranial electrotherapy stimulation (n=18) experienced a significant reduction in post-SCI neuropathic and musculoskeletal average daily rating of pain intensity (p=0.03); however, there was no significant reduction in pain as noted on the Brief Pain Inventory (BPI).
Capel et al. (2003) reported transcranial electrostimulation resulted in lower pain scores on the McGill Pain Questionnaire for those in the treatment group (n=15), while those in the control group (n=15) reported no change. No statistical differences were noted across different pain types, although the authors did comment that subjects had greater relief of visceral pain following each active 4-day treatment phase of the study. Transcranial electrostimulation was associated with a reduction in the use of analgesics and antidepressants.
Fregni et al. (2006)found similar results after examining the effects of transcranial direct current stimulation (tDCS) on central neuropathic pain. The treatment group (n=11), those receiving active tDCS for 5 consecutive days, experienced a significant reduction in pain relief over time (p<0.0001) compared to those receiving sham treatments (n=6)
Table: Static Magnetic Field Therapy Post-SCI Pain
Static Magnetic Field (SMF) therapy has been studied as a treatment for pain post SCI. Panagos et al. (2004) in a pre-post study involving 8 individuals, on average 12 years post injury, found that placing a static field magnet of 500 gauss over a self-identified ‘trigger point’ resulted in patients reporting less stabbing, sharp and tender pain (p<0.05); however, there was no significant change noted on a VAS pain severity scale. These results are severely limited by the uncontrolled study design and relatively few study participants.
Transcutaneous Electrical Nerve Stimulation (TENS) is commonly used as an electroanalgesic and has been shown to be efficacious in the treatment of chronic musculoskeletal pain (Johnson et al. 2007). TENS is believed to preferentially stimulate large alpha sensory nerves and reduce pain at the presynaptic level in the dorsal horn of the spinal cord through nociceptive inhibition (Cheing et al. 1999).
Davis and Lentini (1975) reported on a series of patients (n=31) in whom transcutaneous nerve stimulation was applied to painful areas. Among those with a thoracic (n=11) or caudal level injury (n=16), only 36% reported that the treatment was successful in reducing pain at the injury site; meanwhile, none of those with a cervical injury (n=4) experienced any reduction in pain. In general, TENS was not deemed effective for radicular or below-level injury site pain.
Transcranial magnetic stimulation (TMS) is a noninvasive and relatively safe technology where electromagnetic currents in a coil produces magnetic pulses which crosses the cranium and induces neuron depolarization (Defrin et al. 2007). Magnetic stimulation of the motor cortex has been shown to attenuate post-stroke pain (Migita et al. 1995).
Table: Transcranial Magnetic Stimulation
Defrin et al. (2007) studied transcranial magnetic stimulation (TMS) and found both real and sham TMS stimulated treatments significantly reduced pain. The real TMS treatment resulted in a much greater reduction in pain (and depression) scores at follow-up.
Pharmacological interventions are the standard treatment for SCI pain. The limited effectiveness of non-pharmacological treatments has contributed to increasing use of pharmacological interventions to deal with what is often very severe and disabling pain.
Table 16 Pharmacological Interventions and Post-SCI Pain
Widerstrom-Noga and Turk (2003),not unexpectedly, found that SCI patients with more severe pain, in more locations, those with allodynia or hyperalgesia, and those in whom the pain was more likely to interfere with activities were more likely to use pain medications.
Trials of simple non-narcotic analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen or non-narcotic “muscle relaxants” are common clinical practice in SCI pain. Unfortunately, these medications are often ineffective in complete SCI neuropathic pain relief and have potential risks such as gastric ulceration with prolonged use.
For neuropathic or “central” pain seen following SCI, psychotropic drugs such as antidepressants and anticonvulsants are reportedly the most effective (Donovan 1982). Despite increasing popularity, few drugs (with the exception of Gabapentin and pregabalin) have regulatory approval for use in neuropathic pain and selection for individual patients is largely based on anecdotal evidence, of off-labelled use.
Anticonvulsant medications are often utilized in treating neurogenic or deafferent pain following SCI based on the theory that these drugs alter sodium conduction in uncontrolled hyperactive neurons (“convulsive environment”) in the spinal cord. Carbamazepine has been reported as being somewhat effective in the paroxysmal, sharp, shooting pain of trigeminal neuralgia (Swerdlow 1984). Gibson and White (1971) described relief resulting from carbamazepine treatment in two cases of L2 and T8 SCI with intractable pain below the level of SCI. A similar effect of Carbamazepine (200 mg 2 x daily in combination with Amitriptyline 50 mg 3 x daily) was reported in a complete C8 patient with dysesthesia below the level of the injury (Sandford et al. 1992). Again, controlled studies utilizing these drugs in SCI pain are lacking with the exception of gabapentin and pregabalin.
Gabapentin and pregabalin are now regarded as first-line treatments of neuropathic pain (Ahn et al. 2003; Moulin et al. 2007). Gabapentin and pregabalin have been recommended as first line treatments for neuropathic pain in Canadian and international guidelines (Gajraj 2007). The mechanism of action for Pregabalin and Gabapentin is through binding the alpha-2 delta receptors in the central nervous system. These receptors are present on the presynaptic nerve terminals. When bound by gabapentin or pregabalin they decrease the influx of calcium into the presynaptic terminal there by decreasing the release of excitatory neurotransmitters. Gabapentin and pregabalin appear to potentiate GABA effects centrally through enhancement of GABA synthesis and release. Levendoglu et al. (2004) note that neuropathic pain is ultimately generated by excessive firing of pain-mediating nerve cells, insufficiently controlled by segmental and nonsequental inhibitory circuits. Gabapentin and pregabalin work by increasing GABA and reducing the release of glutamate thereby suppressing the sensitivity of N-metyl-D-asparate (NMDA) receptor. This has been shown to reduce neuronal hyperexcitability recorded at the spinal dorsal horn near the level of injury (Ahn et al. 2003). Gabapentin and pregabalin are relatively well tolerated with only a few transient side effects, lack of organ toxicity, and no evidence of significant interaction with other medications (Levendoghu et al. 2004, Gajraj 2007).
Table: Anticonvulsants for SCI Pain
Gabapentin
To et al. (2002)studied the impact of gabapentin on pain in a case series of 44 SCI patients with neuropathic pain and reported a significant decrease (p<0.001) in visual analogue pain scale (VAS) in 76% of subjects. Tai et al. (2002) studied the impact of gabapentin for pain treatment in a small RCT of only 7 patients. There was a significant reduction of “unpleasant feeling” with gabapentin vs. placebo (p=0.028) while “pain intensity” and “burning pain” only trended to significance (p=0.094 and 0.065, respectively) and no differences were detected for other pain descriptors such as “sharp”, “dull”, “cold”, “sensitive”, “itchy”, “deep”, “surface”. Levendoglu et al. (2004) in a cross-over design of 20 paraplegics with neuropathic pain > 6 months found that Gabapentin was more effective (p<0.05) than placebo in reducing neuropathic pain. Ahn et al. (2003) in a before and after trial found that Gabapentin was effective (p<0.05) in decreasing neuropathic pain which was refractory to conventional analgesics for SCI patients with pain < 6 months and > 6 months and that the impact was greater for those patients with pain < 6 months in the most recent pain group. Putzke et al. (2002) found that, among the 21 patients who answered their questionnaire, 67% (n=14) reported a reduction in pain while on gabapentin.
Rintala et al (2007) was the only study to report Gabapentin to have no benefit over placebo in the treatment of pain in spinal cord injury. This study may have been complicated by the fact that the placebo treatment was dimenhydramine and not a true inert placebo and the number of subjects was only twenty two.
Pregabalin
Pregabalinis an analogue of the neurotransmitter gamma-aminobutyric acid (GABA) with demonstrated analgesic, anxiolytic, and anticonvulsant activity. It’s mechanism of action is similar to gabapentin, but it has a higher affinity for the alpha-2-delta receptor and has linear pharmacokenetics. Sidall et al (2006) published the results of a double blind randomized control trial evaluating the use of flexible dose pregabalin in the treatment of neuropathic pain in spinal cord injury. A total of 137 subjects with central neuropathic pain post spinal cord injury participated. The primary outcome was the VAS pain scale and secondary outcomes included sleep interference and anxiety scales. Seventy patients were randomized to receive pregabalin and 67 patients received placebo. At the end of the trial the pregabalin treated patients had significantly more pain relief. The pregabalin treated subjects also reported significantly improved sleep and anxiety. Side effects were mild and transient and included dizziness, drowsiness and edema (similar to gabapentin).
In a RCT conducted by Vranken et al. (2007) patients in the treatment group received escalating doses of pregabalin (150-600 mg daily), while those in the control group received a placebo. Subjects in the treatment group reported a significant decrease in pain (p<0.01), along with improvements in the EQ-5D VAS and utility scores (p<0.01), as well as the Bodily Pain subscale of the SF-36 (p<0.05), relative to the control group.
Lamotrigine
Finnerup et al. in 2002 studies the effects of lamotrigine on post SCI pain. Although the overall result showed no difference between placebo and lamotrigine, there was a significant reduction in pain in the incomplete spinal cord group.
Levetiracetam
Finnerup et al. (2009) conducted a randomized, double blind, crossover trial of levetiracetam in SCI individuals with pain. Participants were placed in either the levetiracetam or placebo group for 5 weeks and then crossed over after a 1 week washout period. This study found no significant difference between the levetiracetam and the placebo treatment group in improving pain intensity (p=0.46).
Valproate
In a double-blind cross-over study (n=20), Drewes et al. (1994) examined the effects of a 3 week treatment course of valoproic acid on chronic central pain in individuals who had sustained a SCI. Overall, they found no significant differences between the control and treatment groups; however, there was a trend towards improvement in the treatment group.
Table 18 Summary of Anticonvulsant Pain Treatment Post SCI
Tricyclic antidepressant drugs are thought to modulate pain by inhibiting the uptake of norepinephrine and serotonin in the CNS. Sandford et al. (1992) have suggested that the tricyclic antidepressants exert an analgesic effect by making more serotonin available in the CNS, thereby potentiating the inhibitory action of the dorsal horn of the spinal cord. Unfortunately, these medications are often sedating and produce a variety of anticholinergic side effects.
The partial effectiveness of tricyclic antidepressants (TCA) in some SCI patients with dysesthetic pain suggests that this drug is simply affecting the pain by treating the depression. Sandford et al. (1992) noted that pain and depression maybe chemically linked. Depression can lower pain thresholds or pain tolerances thereby increasing the patient's experience of pain. However Max et al. (1987) were able to show that tricyclic antidepressants (TCA) had analgesic properties despite low doses or short treatment cycles with analgesic activity occurring independent of mood changes.
Davidoff et al. (1987) reported trazodone's lack of effectiveness in relieving pain in 19 SCI patients with chronic dysesthetic pain, using a double-blind placebo controlled trial. Trazodone reportedly selectively inhibits serotonin and norepinephrine uptake in a ratio of 25:1, and is thought to produce greater analgesia and less anticholinergic side-effects compared to non-selective agents such as amitriptyline.
Table: Tricyclic Antidepressants in Post-SCI Pain
Tricyclic antidepressants are often recommended for the treatment of neuropathic pain following non-SCI causes. Therefore, it is important to study the use of tricyclic antidepressants in the treatment of post-SCI pain.Cardenas et al. (2002) reported no significant difference in randomized spinal cord injury patients receiving either amitriptyline or placebo given 1-2 hours before bedtime for a period of 6 weeks. Heilporn (1977) using combinations of melitracin and TENS reported relief of pain in 8 of 11 SCI patients with dysesthetic pain. In an interesting study by Rintala et al. (2007), amitripyline was no better than gabapentin in depressed and nondepressed subjects but was better than diphenhydramine for depressed subjects only.
Davidoff et al. (1987), in a 6 week double-blind placebo-controlled trial, found that trazodone was ineffective at relieving pain in 18 SCI patients with chronic neuropathic pain
Anaesthetic medication such as lidocaine and ketamine are sodium channel blockers and can be delivered by a number of routes. Ketamine is a noncompetitive N-methyl-D-Aspartate (NMDA) receptor antagonist can be administered epidurally and intrathecally (and orally) to treat neuropathic pain syndromes (Hocking & Cousins 2003).
Table: Anaesthetic Medications for Post-SCI Pain
Lidocaine
Given the severity of post-SCI pain, treatments such as lumbar epidural and subarachnoid infusions or anaesthetics are sometimes utilized and there is some evidence for these treatments. Loubser and Donovan (1991) conducted an RCT of 21 patients who were provided 2 separate lumbar subarachnoid injections of placebo and 5% lidocaine in dextrose. Following the lidocaine injection (n=13) there was a significant mean reduction in pain (p<0.01) for an average of 2 hours despite the fact that 8 patients showed no changes. However, this treatment provided short-term relief of pain only. The authors regarded the value of this treatment as more a diagnostic procedure than a therapeutic one.
Attal et al. (2000)reported on 15 patients who received lidocaine intravenously and experienced a greater reduction in pain than those who received placebo, with an effect lasting up to 45 minutes post injection, and a reduction in the intensity of brush-induced allodynia and mechanical hyperalgesia. In a RCT study by Finnerup et al. (2005) those patients who received lidocaine intravenously (n=24) in two treatment sessions 6 days apart reported significantly less pain than those who did not receive intravenous lidocaine.
Kvarnstrom et al. 2004 found no evidence for the effectiveness of intravenous lidocaine in reducing neuropathic pain when compared to placebo.
Mexilitine
Chiou-Tan et al. (1996) provided 15 SCI individuals with either oral mexiletine (an orally administered derivative of lidocaine) or placebo (150mg 3 x daily) in a double-blind cross-over RCT. There was no appreciable improvement in pain severity, as measured either on a VAS or using the McGill Pain Questionnaire, within either group.
Ketamine
In one RCT of 10 subjects, Kvarnstrom et al. (2004) found ketamine was successful in reducing spontaneous neuropathic pain post SCI. Eideet al. (1995)in an RCT of intravenous ketamine hydrochloride (NMDA receptor antagonist), alfentanil (m-opioid receptor agonist) or placebo were provided as combination of bolus and continuous intravenous infusions. There was a significant benefit to ketamine or alfentanil vs. placebo for allodynia. Alfentanil reduced wind-up pain compared toplacebo but not ketamine overall; however, there was a high correlation between the serum concentration of ketamine and the reduction in continuous pain and wind-up pain. The effects of ketamine and alfentanil were significant when compared to placebo.
Table 21 Summary of Anaesthetic Treatments Post SCI Pain
Herman et al. (1992) note that baclofen, an α-aminobutyric acid (GABA)B receptor agonist,acts to suppress spasticity in SCI patients centrally within the spinal cord itself. GABA is known to be involved in several analgesics pathways (Savynok 1987) and experimentally induced allodynia has been shown to be suppressed by baclofen (Henry 1982). However, baclofen, by treating spasticity, may reduce the musculoskeletal pain associated with spasticity. Continuous intrathecal infusion of baclofen can be effective, when oral baclofen is ineffective, in further reducing post-SCI spasticityand/or pain (dysesthetic, musculoskeletal, neurogenic) (Penn & Kroin 1987; Herman & D’Luzamsteg 1991; Boviatsis et al 2005; Plassat et al 2004). For an in-depth discussion of intrathecal baclofen and it’s effects on spasticity in SCI, please refer to Spasticity chapter.
Table: Antispastic Medications for Post-SCI Pain
Baclofen
Boviatsis et al (2005) and Plassat et al (2004) presented case series data that reflected improvements in self-reported pain ratings after intrathecal baclofen administration. Herman et al. (1992)in a RCT found that intrathecal baclofen significantly suppressed the dysesthetic (burning) pain among 6 of the 7 subjects (p<0.001). Only one of the placebo patients noted the dysesthetic pain was abolished. Intrathecal baclofen did not have a significant impact on pinch induced pain. Therefore, in this study, intrathecal baclofen appeared to have an impact on post-SCI dysesthetic pain in addition to treating the spasticity. Loubser and Akman (1992) performed a before and after study of implanted Baclofen infusion pumps provided for spasticity. Twelve (12) of 16 patients described pre-existing chronic pain but there was no significant difference in the VAS neurogenic pain symptoms at 6 and 12 months (p=0.26) while musculoskeletal pain symptoms and pain severity decreased in conjunction with control of spasticity in 5 of 6 patients. In this study, it appeared musculoskeletal pain was reduced more with intrathecal baclofen, presumably by reducing spasticity.
Hence it would appear that intrathecal baclofen improves chronic post-SCI pain but the actual mechanism has not been adequately established. There is evidence that baclofen infusion pumps may be helpful for both neuropathic and musculoskeletal pain after SCI (Loubser et al. 1996). However, studies have shown that intrathecal baclofen only reduces SCI pain when pain is related to muscle spasms (Coffee et al. 1993; Meythaler et al 1992). Suppression of central pain through baclofen antagonism of substance P has been postulated (Herman et al 1992)
Motor Point Phenol Block
In a case series, Uchikawa et al. 2009 followed 7 spinal cord injury individuals with spastic shoulder pain underwent a motor point phenol block procedure. A significant improvement in VAS shoulder pain was seen post injection (p<0.05).
Botulinum Toxin
Marciniak et al. (2008) treated 29 SCI patients with Botulinum toxin type A injections to treat focal spasticity. Pain was improved by 83.3%.
To date there are few research studies examining opioids in the treatment of SCI pain. There is a substantial body of research investigating the benefits of opioid analgesics in the treatment of non-cancer chronic pain and some of those studies examined the impact of opioids on neuropathic pain. There are no studies employing opioid analgesics in post-SCI pain. Furton et al (2006) conducted a meta-analysis of effectiveness and side-effects of opioid analgesics for chronic non-cancer pain. Their meta-analysis found that opioids reduced pain and improved functional outcomes when compared to placebo for both nociceptive and neuropathic pain syndromes. Strong opioids (oxydone and morphine) were significantly superior to naproxen and nortriptyline for pain relief but not functional outcomes. Weak opioids (propylene, tramadol and codeine) did not significantly do better than NSAIDS or tricyclic anti-depressants for either pain relief or functional outcomes (Furton et al. 2006). The same authors found that clinically, only constipation and nausea were significantly more common with opioids (Furher et al 2006). The big concern with opioids is of course addiction or opioid abuse. Unfortunately, as Furton et al. (2006) notes in their meta-analysis, the existing randomized trials were not designed to evaluate addiction.
Table: Opioids for Post-SCI Pain
Attal et al. (2002) found the intravenous morphine titrated to maximal tolerated dosage, significantly reduced dynamic mechanical allodynia but not necessarily spontaneous or burning pains. Oral opioids remain untested in this population.
Norrbrink and Lundeberg (2009) conducted a double-blind RCT to assess the efficacy of tramadol in 35 SCI individuals diagnosed with at- or below- level neuropathic pain. The authors reported significant differences between the two group pain ratings (p<0.05). Tramadol was also found to be effective in improving anxiety, global life satisfaction and sleep quality in individuals with post SCI pain (p<0.05). However, no significant improvement was seen in pain unpleasantness and depression levels.
Eide et al. 1995 randomly assigned individuals with chronic SCI pain into three groups receiving ketamine hydrochloride, alfentanil (m-opioid receptor agonist)or placebo treatment. The study found alfentanil and ketamine effectively reduced SCI pain compared to placebo treatment (p<0.04, p<0.01); however no difference was seen between the two treatments in overall pain. Alfentanil significantly reduced wind up like pain while ketamine did not.
Wade et al. (2003) note that delta-9-tetra hydrocannabinol (THC) and other cannabinoids have been shown to improve both tremor and spasticity in animal models of multiple sclerosis supported by anecdotal reports that cannabis relieves some of the troublesome symptoms of multiple sclerosis and spinal cord injury (Dunn & Davis 1974; Petro & Ellenberger 1981; Ungeleider et al. 1987; Meinck et al. 1989; Martyn et al. 1995; Consroe et al. 1997; Baker 2000). There is a clinical impression that marijuana smoking is very common among patients post-SCI; however, there are social and legal implication to its use and medical concerns about smoking as a delivery system.
Table: Cannabinoids and Post-SCI Pain
Hagenbach et al. (2007) conducted a study examining primarily the effectiveness of THC in improving spasticity and secondarily, in improving pain with SCI individuals. In the first phase of the study, 22 individuals received 10mg of oral THC which was then dose titrated until maximum tolerance or treatment dose was reached for 6 weeks. The study found a significant reduction in the pain of SCI individuals post treatment (p=0.047). The third phase of the study involved a double blind randomized control trial which included 13 of the previously mentioned individuals receiving either individual maximum treatment dosage previously determined or a placebo dose. In this phase, Hagenbach et al. (2007), found individuals in the treatment group had no significant pain reduction compared to those in the placebo group.
Given that marijuana has anecdotally been thought to have benefits for post-SCI pain, Wade et al. (2003) conducted an RCT of sublingual 2.5 mg tetrahydrocannabinol (THC) and/or cannabidiol and found that it helped to reduce pain, muscle spasm, spasticity and sleep in a group of largely multiple sclerosis patients with neuropathic pain. It is of note that only a small percentage of the patients in this study had spinal cord injuries hence did not meet inclusion criteria. Cannabinoids are a promising treatment, which would benefit from other studies.
Clonidine is an alpha-2 adrenoceptor agonist which has been shown to activate spinal receptors that reduce responses to painful stimuli (Yaksh 1985). Ackerman et al. (2003) note that clonidine inhibits nociceptive impulses by activating alpha-2 adrencoceptors in the dorsal horn of the spinal cord (Rainov et al. 2001). The anti-nociceptive effects of clonidine are thought to be mediated via inhibitory interaction with pre- and post-synaptic primary afferent nociceptive projections in the dorsal horn (Osenbach and Harvey 2001) and possibly by inhibition of substance P release (Hassenbusch et al. 1999; Ackerman et al. 2003). Ackerman et al. (2003) noted selective alpha-2 adrenergic antagonists (e.g. Yohimbine) have been shown to reverse clonidine-induced analgesia (Osenbach & Harvey 2001). Teasell and Arnold (2004) were able to show that venous alpha-adrenoceptor hyperresponsiveness was present in patients with RSD, in diabetic peripheral neuropathy (Arnold et al. 1993) and below the level of lesion in quadriplegics (Arnold et al. 1995). They speculated that this alpha-adrenoceptor hyperresponsiveness was in fact due to alpha-2 adrenoceptor dysfunction leading to overstimulation of the post-synaptic alpha-1 adrenoceptor peripherally. This would fit with the observation that clonidine reduces pain post-SCI below the level of the lesion, presumably through its alpha-2 adrenoceptor agonist function.
Ackerman et al. (2002) noted that clonidine may be useful for patients who are non-responsive to opioids. Clonidine appears to work synergistically with opioids to provide pain relief (Plummer et al. 1992; Tollerida et al. 1999; Siddall et al. 2000; Osenbach & Harvey 2001)
Table: Clonidine for Treatment of SCI Pain
Siddall et al. (2000) in a RCT/cross over trial of 20 subjects with post-SCI neuropathic pain. Intrathecal morphine clonidine or placebo was given at the lumbar level. Once the subject received satisfactory pain relief or drug side effects they were given a mixture of clonidine and morphine. Morphine or clonidine showed a trend in pain reduction, which was not statistically significant but when the combination of morphine and clonidine was administered there, was a significant reduction in pain. Siddall et al. (2000) did postulate that by administering half the effective minimum dose of clonidine and morphine together resulted in a synergistic addictive effect above the simple summing up of each drug in isolation. Uhle et al. (2000) in a study of study 10 patients were given morphine followed by clonidine via a medical pump. Patients when given clonidine experienced a good to excellent reduction in their pain.
Capsaicin is an active alkaloid in hot peppers. It has been successfully used to reduce pain in herpes zoster, diabetic neuropathy and post-mastectomy pain syndrome (Sandford & Benes 2000). It works as an inhibitor of substance P.
Table: Topical Capsaicin in Post-SCI Pain
Topical capsaicin was used to treat radicular post-SCI pain for 1-2 weeks (Sandford & Benes 2000). Patients showed improvement in pain and 2 of the 8 patients were still improved for over 2 years.
Spinal cord stimulation has been used to try to treat intractable pain. The procedure is both expensive and invasive.
Table: Spinal Cord Stimulation Post SCI
Cioni et al. (1995)in a case series reported inserting epidural electrodes percutaneously over the posterior columns of the spinal cord to allow for spinal cord stimulation. During spinal cord stimulation, 22 patients reported parasthesias overlapping the painful area. 9 patients reported 50% pain relief and 3 patients experienced no pain relief.
Table: Dorsal Longitudinal T-Myelotomy Post-SCI Pain
Livshits et al. (2002) conducted a case control study comparing two approaches of dorsal longitudinal T-myelotomy (i.e., Pourpre vs. Bischof II) with respect to their effectiveness in reducing pain and spasticity in people with SCI, initially refractory to more conservative approaches (N=40). Systematic follow-up assessments at 6 months, 5 and 10 years were conducted. In this study, significant pain reduction was obtained with either of these surgical techniques, as measured using scores obtained from the Short Form – McGill Pain Questionnaire, the Present Pain Intensity scale, and a visual analog scale, but this appeared to be more notable with the Pourpre versus the Bischof II procedure.
Dorsal rhizotomy is a procedure where the sensory roots are divided either intradurally or extradurally. According to Nashold (1991) a single one or two level root rhizotomy may be appropriate when the pain is localized as in those patients with paraparesis and single root pain. Moreover, Nashold (1991) reported the Dorsal Root Entry Zone (DREZ) procedure was more likely to be successful in these patients.
Table: Dorsal Root Entry Zone Procedure Post-SCI Pain
Notably, Nashold et al. (1990) reported 14 of 18 individuals (77%) with paraplegia who underwent cyst drainage and the DREZ surgical procedure reported pain relief following surgery. In general, approximately 50% or more of the patients across these case series achieved greater than 50% pain relief or experienced no pain-related activity limitations and no need for narcotics following the surgery (Nashold et al. 1990; Sintou et al. 2001; Sampson et al. 1995; Friedman & Nashold. 1986; Spaic et al. 2002; Spaic et al. 1999; Sindou Rath et al. 1997). However, all of these were retrospective, uncontrolled reports with obvious methodological limitations, such as ill-defined eligibility criteria (i.e., potential selection bias) and inadequate outcome measurement which limits the generalizability of the results.
Sympathectomy is not recommended for pain following SCI (Nashold 1991). As mentioned previously, sympathetic blockade and sympathectomy have reportedly failed to relieve the central pain of SCI (White 1969; Melzack 1978; Friedman 1986).
Hazouri and Mueller (1950) described three selected cases of patients with intractable root pain, subsequent to severe trauma to the cauda equina which resulted in paraplegia (L2-4 lesions). All three patients demonstrated a distinct increase in the threshold for perception of pain and "an even more remarkable increase in the threshold for reaction to pain." Lateral spinothalamic tractotomy in all three of these patients resulted in complete relief from pain. Threshold studies subsequent to the tractotomy "revealed a striking return of perception and reaction thresholds to a normal range."
This procedure can be performed openly or percutaneously. Anterior spinothalamic tracts subserving pain and temperature function are sectioned, often requiring a bilateral approach. Spinal cordotomy is an option but is rarely employed and there is little evidence that it works.
Pain following SCI is quite common. The most common type of pain post SCI is central or neuropathic in nature characterized by a dysesthetic, burning pain below the level of SCI. Borderzone or segmental pain is much less common; occurring along the border between normal and absent sensation. The precise etiology of central/neuropathic or borderzone segmental pain is not known. There is some evidence suggesting an association may exist between the central or neuropathic dysesthetic burning pain and abnormalities of the sympathetic nervous system. Musculoskeletal pain, either secondary to the original trauma or to overuse is both common and well understood. Unfortunately, the management of central or neuropathic pain remains difficult and largely ineffective.