Spinal Cord Injury

Spring 1998
Volume 9, Number 1

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Introduction. Spinal cord injury (SCI) can cause paralysis, sensory impairment, autonomic nervous system dysfunction, bowel, bladder, and sexual dysfunction. These impairments may lead to immobility and physical dependency that can alter lifestyle and self-esteem. The addition of chronic, intractable pain to these impairments can be devastating. Chronic pain superimposed on SCI can virtually drain the individual of strength, motivation, and will. For the SCI survivor who already faces functional loss, severe pain can further restrict the diversional activities that are available, making it impossible for the individual to even temporarily escape his or her pain.1

Chronic SCI pain is known to be variable and difficult to accurately measure by any objective means. Over the last 40 years, the reported prevalence of severe or disabling chronic pain in SCI has ranged from 18% to 63%.2 Medical progress has given SCI patients greater longevity and improved overall health, allowing chronic pain to emerge as a major complication in this population. Lundquist et al3 reported severe pain to be the only complication they tracked related to diminished quality of life. For many, it is the most difficult problem with which they must cope.

Categorization. Pain of any origin is difficult to assess, categorize, and treat because analysis relies on the patient’s own subjective and variable perceptions. Chronic SCI pain is especially difficult to accurately measure. Historically, it has been neither well investigated nor clearly understood. These difficulties have led to limitations in study design that restrict the validity of their conclusions. The lack of a widely accepted SCI pain classification scheme has limited the comparability of the pain interventions studied. Accordingly, many clinicians do not have a clear idea of how to approach the problem diagnostically, or how to pursue treatment. Tunks4 observed that, “We must not fool ourselves, we have many impressions, but few facts regarding treatment of SCI pain.”

Over the past 40 years, investigators and clinicians have attempted to categorize SCI pain using a variety of schemes. Classifications have usually been based on the postulated origin, clinical features or localization of the pain.5 For example, nociceptive pain localized above the level of spinal cord injury can be contrasted to radiating neuropathic pain at the level of injury, or to diffuse neuropathic pain below the level of injury. There is very little evidence that characteristics of the injury itself, such as level, completeness, or etiology, are associated with the development or severity of pain. Distinguishing chronic SCI pain from acute or acute persistent pain is vital in providing the most appropriate treatment for a patient.1

Acute Pain. Acute pain after SCI is usually nociceptive in origin and localized above the injury level. It usually occurs from either the physical or mechanical nature of the injury or some primary disease process. With acute pain there is evidence of some peripheral source or exogenous source of the noxious stimuli. Acute pain responds to an accurate clinical diagnosis and treatment. If the medical, surgical, and physical problems can be eliminated, so can the pain.

The initial differential diagnostic considerations in acute SCI pain include spinal instability from fractured vertebrae or torn ligaments and localized infection. Delayed acute pain problems include pseudoarthrosis, peripheral bone and soft-tissue injury, peripheral nerve injury with neuritis, visceral disorder, and heterotopic ossification.

Acute-persistent Pain and Cystic Myelopathy. Acute-persistent pain or acute-recurrent pain tends to be localized in the injured area of the spine and is frequently exacerbated by physical activity. It is often described as a localized dull ache or a sharp, penetrating pain, and often occurs in the setting of ongoing pathology. Sources of acute-persistent pain in SCI include degenerative joint disease (DJD) of the spine, tumors, and nerve root pain (radiculopathy).

Cystic myelopathy is a common source of acute-persistent pain in SCI caused by the development of cystic changes in the spinal cord which ascend from the zone of injury. Arachnoiditis and tethering of the cord to the spinal canal are important predisposing factors. Destruction of spinal cord tissue from gradually increasing cystic pressure, especially in the dorsal horn region, can cause increasing pain. Other signs and symptoms suggesting cystic myelopathy include progressive motor/sensory losses, exacerbating spasticity, autonomic hyperreflexia, hyperhidrosis, and Horners1 Syndrome. A thorough history and physical examination coupled with a magnetic resonance imaging of the spinal cord provides the most accurate diagnosis of cystic myelopathy. Treatment of cystic myelopathy is well described later in this article.

Chronic Pain. Chronic pain after SCI is most often neuropathic in origin, experienced below the level of injury. It occurs equally with complete and incomplete lesions, and tends not to follow a dermatomal distribution. It is most frequently perceived as a burning, tingling, electric-like, or aching sensation. This neuropathic pain is generated within the central nervous system and continues long after exogenous or peripheral sources of acute pain have resolved. It may be the most difficult of the SCI pain syndromes to treat.

The central nervous system focus of chronic neuropathic SCI pain occurs from the deafferented zone of the injury, the area exhibiting impaired sensory input from the peripheral nervous system. Scarring, arachnoiditis, abnormal axonal sprouting, and cord tethering in the dorsal horn region may have developed. These anatomical changes may cause alterations in the normal physiology of the cord, including abnormal burst firing, altered neuropeptide concentrations, ephaptic spread from sympathetic fibers to pain fibers, and altered function of descending inhibitory pain pathways that terminate in the dorsal root entry zone (DREZ) of the spinal cord.4 Normal concentrations of opioid peptides and GABA-like substances in the substantia gelatinosa of the spinal cord may be reduced. Neurons within the spinal cord that normally carry pain impulses may be subjected to increased facilitation or reduced inhibition that allows painful stimuli to spread to supra-spinal centers.

Abnormal burst firing from dorsal horn cells rostral to an area of spinal cord trauma has been demonstrated by Loeser, et al.6 Abnormal electrical activity of secondary interneurons in the substantia gelatinosa was noted after deafferentation on experimental animals by Nashold, et al.7 This uncontrolled repetitive neuronal firing in the spinal cord has been described as “central neurophysiologic epileptiform activity” by Crue,8 and likened to a convulsive syndrome of the spinal cord by Fibson and White.9 At the cortical level, the existence of a “neuromatrix” has been described which may act as the substrate of sensory experiences which can be modified by afferent stimuli or their absence. Cortical memory of body parts may generate the perception of pain where afferent stimuli are totally absent after SCI.10

Treatment of Chronic SCI Pain. Chronic SCI pain is central neuropathic pain that requires centrally directed treatment.8 Treatment options begin with conservative pharmacological, medical and physical therapies, progress through neuroablative procedures, and finally utilize narcotics if warranted. In general, treatment involves attempts to resolve abnormal central nervous system activity with centrally acting medications or centrally directed neurosurgical procedures. Although peripherally directed treatments are not definitive, they may be used to help reduce noxious stimuli that act as exacerbating factors of central pain.

Chronic SCI pain is often recalcitrant and refractory to non-surgical procedures.11 Nonetheless, when considering treatment options it is best to start conservatively and only use more invasive surgical procedures as dictated by continuing complaints. This approach should be attempted with all patients, as a small number will experience satisfactory relief following conservative measures. In addition, it may be psychologically important for patients to know they have tried all the less “risky” treatments before proceeding with surgery.

Usually, a multidisciplinary program is needed for effective treatment of chronic SCI pain. The team usually consists of physicians with experience in pain management, rehabilitation nursing staff, psychologists, and physical, occupational, and recreational therapists. An eclectic program incorporating all the options provided by a comprehensive pain clinic is required to optimize outcome. Treatment options for chronic SCI pain fall into the following categories: 1) general health promotion and relief from exacerbating factors, 2) non-narcotic pharmacologic, 3) physical, 4) surgical, and 5) narcotic pharmacologic.

General Health Promotion and Relief From Exacerbating Factors. Rehabilitation physicians and nursing staff provide the care and education needed to improve the patients general health and reduce factors that exacerbate chronic SCI pain. The physician is responsible for treating general medical problems including those complications common to patients with spinal injuries, such as pulmonary and genitourinary infections, autonomic hyperreflexia, spasticity, and heterotopic ossification. The nursing staff assesses the patient’s skin, bowel, and bladder management, and recommends programs to prevent urinary tract infections, decubiti, and bladder or bowel distention. Educating the patient in proper self-management techniques and general health maintenance instills a feeling of well being and heightened confidence. An improved attitude can reduce stress and anxiety, and may help to increase levels of natural opiates.

Non-narcotic Pharmacologic Treatment. The most commonly used centrally acting non-narcotic medications for the treatment of chronic SCI pain include antidepressants, anticonvulsants, and antipsychotics. There has been a lack of scientifically designed, controlled, double-blind studies with adequate follow-up that show these medications are consistently reliable in providing permanent relief of chronic SCI pain. Hence, many pain experts believe these medications are ineffective in providing pain relief.12 Nevertheless, numerous less rigorous studies suggest patients have experienced subjective pain reduction when using these medications. They appear to be especially effective in combination, presumably due to complimentary mechanisms of action.13 The ease of administration, relative lack of side effects, and low cost of these medications usually warrant a trial for efficacy.

Antidepressants. The most commonly used antidepressants for neuropathic pain, including chronic SCI pain, are tertiary amines. Commonly referred to as tricyclic antidepressants, these include amitriptyline, nortriptyline, doxepin, and imipramine.14 The exact mechanism of actual pain relief is believed to involve interference with the synaptic reuptake of the neurotransmitters dopamine, norepinephrine, and serotonin. This may reduce activity in afferent pain pathways with serotonergic synapses, and to make large quantities of norepinephrine available in the descending pain inhibitory pathways that terminate in the substantia gelatinosa of the dorsal spinal cord where hyperexcitable neurons may exist.13, 14

Interestingly, the analgesic benefits of antidepressants do not seem to be mediated by an antidepressant effect. Atkinson15 notes that maximum pain relief from antidepressant medications for diabetic neuropathy occurred within 2 weeks and was achieved at half the drug concentrations usually required for antidepressant activity. No positive correlation exists between improving chronic pain symptoms and drug concentration levels. However, obtaining pain relief at lower serum concentrations decreases the possibility of adverse effects, which includes sedative, anticholinergic, orthostative, sexual dysfunction, and weight gain.

Choosing of the most appropriate antidepressant for a particular patient is largely empirical. Amitriptyline is usually the first choice for a majority of physicians, but proceeding from there remains a trial and error method.

Anticonvulsants. Chronic central neuropathic pain was described earlier as epileptiform activity of uncontrolled hyperactive neurons, or a convulsive syndrome of the spinal cord.8,9 If this is the case, then treatment with anticonvulsants certainly seems appropriate. The 2 most favored anticonvulsants are carbamazephine and phenytoin. More recently approved by the FDA, gabapentin (Neurontin), has been gaining wider use for neurogenic pain with anecdotal clinical success.

The mechanism of action for central pain relief probably involves stabilizing the threshold of hyperexcitablilty of neurons and inhibiting the spread of “central neurophysiologic epileptiform” activity in second order neurons involved in nociception.16 Hitchcock, et al,17 suggest that activation of inhibitory pain pathways in the central nervous system may play a role.

Results using single anticonvulsant therapy in SCI pain have been inconclusive.18 Better results have occurred using a combination therapy of carbamazepine and an antidepressant.19 Again, efficacy of anticonvulsant treatment, either alone or in combination with antidepressants, requires approximately 2 weeks of administration. Adverse reactions may be serious and routine blood count tests are warranted.

Neuroleptics. The use of neuroleptics for chronic SCI pain is more limited,20 perhaps due to physicians desire to avoid the devastating side effects of tardive dyskinesias or neuroleptic malignant syndrome (NMS). Fluphenazine is the most commonly used for treatment of chronic SCI pain. The exact mechanism whereby its therapeutic action is exerted is unknown, but proposals have included an antagonistic effect to dopamine and a potentiation of antidepressant effects.16,20 Combining fluphenazine with an antidepressant has been recommended with anecdotal reports of good pain relief.13, 16

This combined therapy has demonstrated efficacy in treating postherpetic neuralgia, which is somewhat analogous to chronic SCI pain.16, 20 Treatment is best instituted with a low initial dose. As with all medications, the smallest amount that produces the desired result must be carefully determined.

Physical Treatment. This category involves the treatment of chronic SCI pain mainly by mechanical and other physical methods. Physicians, physical, occupational, and recreational therapists provide most of this type of care. Therapists evaluate and treat the patient for mechanical, musculoskeletal, and functional problems that can act as exacerbating factors of chronic SCI pain.

Daily focused range of motion and stretching exercises help reduce spasticity and prevent joint contractures, adhesive capsulitis, and reflex sympathetic dystrophy (RSD). Changes in wheelchairs and seating cushions help prevent decubiti, scoliosis, joint contractures, and inefficient propulsion. Recreational therapy exposes patients to a variety of diversional activities of which they may be capable. These are especially important as resources of modifying pain behavior. In addition, physical therapists administer various modality treatments, such as transcutaneous electrical nerve stimulation (TENS), warm and cool modalities.

Although some researchers have found TENS ineffective in relieving pain,22 some success has been reported in treating chronic SCI pain in patients with TENS, especially those with sensory incomplete injuries.13, 23 This modality appears to work on the gate control theory of pain proposed by Melzack and Wall.24 Skin surface electrodes stimulate peripheral sensory input through large diameter A fibers, activating pain inhibitory interneurons in the substantia gelatinosa or dorsal root entry zone of the spinal cord. This sensory input essentially “closes the gate” of the secondary neuron in pain transmission. Although this may make sense for an intact spinal cord, it raises theoretical questions about effectiveness in a damaged cord. Nonetheless, a trial of TENS therapy is often felt justified because of its possible efficacy, relative lack of adverse side effects, and low cost.

Thermal modalities include superficial warm and cool packs and deep heat with ultrasound. However, none of these are considered definitive treatment for permanent relief of pain because of their peripherally directed mechanism of action, but may reduce other sources of nociceptive input.

Various types of nerve blocks have been tried in treating chronic SCI pain. Peripheral, epidural, and sympathetic nerve blocks have all been in effective in treating this type of pain mainly because of their inability to affect central mechanisms of pain. They can, however, be used as a diagnostic tool for distinguishing peripheral from central pain. They may also be used as a therapeutic tool by reducing peripheral noxious stimuli that can exacerbate central pain.

Dorsal Root Entry Zone Lesions. The zone of dorsal root entry (DREZ) is the substantia gelatinosa of Rolando, a column of small neurons at the apex of the dorsal gray horns throughout the length of the spinal cord. The transmission of messages from peripheral pain receptors is subject to alteration or “editing” in the substantia gelatinosa. In the uninjured state, data for pain is received by the substantia gelatinosa from primary sensory neurons where it may be modified when transferred to secondary pain neurons or tract cells. In the injured or deafferented state, this modifying influence is lost, allowing hyperexcitability and abnormal neurochemistry of secondary pain neurons to develop.7, 25

DREZ surgery is a limited ablative procedure with a high success rate in relieving chronic SCI pain. The effectiveness of creating a DREZ lesion is thought to be due to the destruction of these abnormal secondary neurons in the dorsal horn.7 The surgical procedure involves a laminectomy for exposure of the spinal cord, direct examination and multiple radio frequency lesions for destruction of the DREZ. It is common for lesions to be performed approximately 2 dermatomal levels above and 1 dermatomal level below the level of injury, which implies the possible loss of several sensory levels.

Since the first DREZ surgery was performed in 1975 at Duke University Medical Center, hundreds of subsequent procedures have been performed for deafferentation pain at Craig Hospital and various other centers. Successful pain relief based on specific neurosurgical criteria has been reported at approximately 60% to 90%.26,27 Nashold26 reported better success with patients who had pain in dermatomes just caudal to the level of injury or unilateral pain in comparison to patients with diffuse or burning pain. Edgar27 initially reported greater success on lower thoracic level injuries but more recent experience has demonstrated nearly equal improvement with higher level injuries.

If conservative management has failed to provide a patient with satisfactory pain relief and other causes of chronic pain have been ruled out, neurosurgical treatment should be considered. Neurosurgical treatments consist of neuroablative, and neuroaugmentative procedures. Neuroablative refers to the surgical production of a neurologic lesion that blocks afferent nociceptive pathways, whereas neuroaugmentative refers to procedures that stimulate physiologic activity of pain inhibitory pathways or the production of naturally occurring analgesic substances, such as endorphins.

Prior to the development of DREZ surgery, neuroablative procedures usually failed to relieve chronic SCI pain and frequently produced a higher level of neurological loss and deafferentation. Examples of these procedures include sympathectomy, peripheral neurolysis, dorsal rhizotomy, cordectomy, anterolateral cordotomy, mesencephalotomy, and cingulotomy. Although useful in other settings, these neuroablative procedures failed to provide substantial or long lasting relief in SCI. Ineffectiveness was due in part to their inability to destroy abnormal electrical activity in secondary interneurons and their connections in the damaged spinal cord, as well as the post-lesion augmentation of auxiliary nociceptive pathways.

Patients who are at least 1 year past their date of injury and have tried conservative treatments provided by a comprehensive pain clinic without success should consider this treatment. Complications of this procedure include cerebrospinal fluid leaking, loss of motor/sensory functions, exacerbation of bowel, bladder and sexual dysfunction, and epidural/subcutaneous hematomas. Persistent pain may be due to thalamic imprinting from the hyperexcitable secondary pain neurons.

Dorsal Column Stimulation. This is a neuroaugmentative surgical procedure in which electrodes used to stimulate the dorsal columns of the spinal cord are implanted epidurally to treat chronic pain. Its proposed mechanism of action involves blocking ascending pain pathways and stimulating the production and release of endorphins.28 Theoretically, the electrode leads must be placed where an intact afferent pathway exists to be effective. Before the 1980’s, many technical problems plagued this procedure. There was a very high complication rate of stimulator migration and breakage. Many patients also reported that the vibratory feeling the stimulators produced in their chest or abdomen was uncomfortably intense.30

Improved equipment and implantation techniques, including percutaneous implantation, have reduced the technical problems, but skepticism regarding the procedure s efficacy in reducing chronic pain remains. The best pain reduction results have occurred in cases of failed back surgery syndrome (FBSS), vasculopathic pain, and postherpetic neuralgia.29, 30 At present, it appears to have limited clinical usefulness in central neuropathic pain.30, 31

Narcotics. Opioid treatment for nonmalignant chronic SCI pain should be considered as part of a multidisciplinary pain treatment program in those patients who have not obtained satisfactory relief from either conservative or surgical treatment. Traditionally, opioid use for chronic nonmalignant pain was felt to be unacceptable and many physicians and patients alike remain reluctant to use such drugs for nonterminal conditions.32,33 This reluctance stems from fear of side effects that include impaired function and motivation, the potential for accelerated tolerance, dependency and addiction, peer criticism, and DEA scrutiny. Consequently, when an opioid is finally utilized to treat chronic SCI pain, it is usually too little, too late. Thus, it is important to keep in mind that although these concerns are legitimate and do warrant a healthy respect for narcotics, an unquestioning fear of their usage is not justified.

The under utilization of long-term narcotic use for chronic, nonmalignant pain has been referred to as the “tragedy of needless pain” by Melzack.35 Unfortunately, as with the non-narcotic pharmacologic treatments, a review of the literature gives no evidence of scientifically designed, controlled, double blind studies with follow-up demonstrating narcotic medication as being consistently reliable in providing relief of chronic SCI pain. Generally, both proponents and opponents of long term opioid use in central neuropathic pain have submitted anecdotal data in support of their respective viewpoints. Proponents1 research has suggested that the use of low dose narcotics can provide pain relief without causing serious side effects and without needing to continually escalate the dosage.35, 36 Opponents1 research questions the utilization of long term opioids in treating pain without demonstrable organic pathology, such as neuropathic central pain.37-39 As the controversy awaits declaration based on future controlled, prospective, double blind studies, the use of opioid therapy should not be abandoned.

Methadone is the narcotic of choice for treating chronic SCI pain. It is a synthetic narcotic analgesic with multiple actions quantitatively similar to morphine. It is nearly equipotent with parenterally administered intramuscular morphine. Its relative oral effectiveness is rated as 3 times that of pentazocine, oxycodone, meperidine, codeine, and morphine.35 The advantages of oral methadone include a relatively long half-life with prolonged effectiveness, minimal cognitive dulling as compared to shorter acting opioids, and relative low cost. Adverse reactions, as with other narcotic analgesics, are dose-related and include respiratory depression, sedation, constipation, antidiuretic effect, and reduced libido and/or potency. Interestingly, Foley and Portenoy36 found no clinically significant side effects in 19 patients who had undergone years of methadone or oxycodone therapy for nonmalignant pain.

Methadone can produce dependency of the morphine-type and has the potential for being abused, although only 4% to 9% of all narcotic addicts began using narcotics as “naive patients” treated for pain.35, 36 Tennant, et al40 noted a 5% iatrogenic addiction rate and 17% drug abuse rate. Morgan and Penovich41 noted the drug s prolonged effect produces a mild withdrawal or abstinence syndrome that may pass unnoticed.

Tricyclic antidepressants are frequently used as adjunctive medications to potentiate narcotic analgesia, perhaps by increasing opiate receptor sensitivity. Anecdotal reports suggest a synergistic benefit from combining amitriptyline with a narcotic analgesic for chronic pain relief.15

Before the first dose of methadone a formal contract should be reviewed and signed by the patient and the prescribing physician. Although each patient’s treatment program is designed to meet individual needs, certain guidelines should be standard for all contracts.13, 35, 42

• Patient enrollment in a multi-disciplinary pain treatment program
• Educating the patient in the use of methadone, its potential risks and benefits
• Single physician prescribing responsibility with dispensing limited to a single pharmacy
• Constant monthly visits with careful overall monitoring of the patient
• Intolerance of abuse behavior
• Periodic tapering of drug to assess the patient’s current therapeutic status and response

Hopefully, participation in a supervised narcotic pain treatment program will break the pain behavior cycle. If a patient experiences enough physical and psychological pain relief from narcotics, he or she is more likely to increase physical activity and participation in other treatments. As general health, function, and behavior improve, narcotics may be tapered.

Conclusion. Both pain and its relief are relative and abstract concepts that are influenced by psychological and environmental factors.11, 43 Therefore, evaluating and quantifying the benefits of any single or combined treatment is difficult. We know that treatment is helping when a SCI pain patient states that he is not “hurting” as much as before. Pain relief is usually accompanied by improvement in both function and behavior, but these remain subjective and unreliable, especially in patients with higher levels of SCI. Curing chronic SCI pain is not always possible, but reducing it is. Any reduction in this type of pain increases the possibility of greater participation in daily activities, escape from pain, and improved self-esteem.

Address comments and questions to:

Thomas E Balazy, MD
Craig Hospital/CNS Medical Group
3425 S Clarkson St
Englewood, CO 80113

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