Pain following Spinal Cord Injury

Musculoskeletal Pain

Musculoskeletal pain typically occurs in normally innervated regions rostral to the level of the SCI. Most people who sustain an injury to the spinal cord also sustain trauma to the vertebral column and its supporting structures, including ligaments, muscles, intervertebral discs, and facet joints. This inevitably results in acute nociceptive pain that can be made worse by ongoing spinal column instability. Typically, musculoskeletal pain is related to activity and position. Pain may be referred to the limbs or trunk and can be difficult to distinguish from radicular (nerve root) pain. Flexion and extension plain radiography, computed tomography, and magnetic resonance imaging may help identify spinal instability.

Chronic musculoskeletal pain can occur with overuse or “abnormal” use of the extremities (e.g., with manual wheelchair use and transfers) and is very common in people with paraplegia ( ). Musculoskeletal pain can also occur when there is limited functional use of the extremities, such as persons with tetraplegia, in whom shoulder pain may be due to muscle atrophy and recurrent dislocation ( ). Muscle spasm pain is also common following SCI and may contribute to musculoskeletal pain, particularly in those with incomplete injuries.

Heterotopic ossification (the formation of ectopic bone in soft tissue surrounding peripheral joints) may occur below the level of injury. Acute symptoms may include fever, swelling of the joint, reduced range of motion, and pain. In this setting, other causes, including infection, fracture, venous thrombosis, and pressure ulceration, need consideration. Findings on imaging (including bone scans) and blood tests such as the erythrocyte sedimentation rate and serum alkaline phosphatase level may also be altered.

Visceral Pain

Pathology or altered function in visceral structures located in the chest, abdomen, and pelvis, such as urinary tract infection, renal calculi, and constipation, is a common source of pain in people with SCI ( ). However, the level of the injury will affect the quality of the pain. Therefore, paraplegics may experience visceral pain that is identical to the pain in those without SCI, whereas tetraplegics may experience more vague generalized symptoms of unpleasantness that are difficult to interpret. Visceral pain can be identified by location (e.g., abdomen or chest) and by characteristics of the pain (dull, poorly localized, bloating, and cramping), which may be intermittent or spasmodic.

The diagnosis of visceral pain is often difficult to make when sensory input from visceral structures is disturbed. If investigations fail to find evidence of visceral pathology and treatments directed at visceral pathology do not relieve the pain, it is reasonable to consider whether the pain is neuropathic rather than visceral.

Neuropathic Pain

A redefinition of neuropathic pain has recently been proposed ( ). This redefinition emphasizes the need to demonstrate pathology within the nervous system that can plausibly explain the pain. Although the presence of central nervous system damage is inherent following spinal cord injury, patients do not always report pain. A diagnosis of neuropathic pain therefore remains reliant on the clinical features (history and examination) of the person reporting pain. Even though the history and bedside examination remain fundamental to the diagnosis of neuropathic pain, screening questionnaires ( ) and confirmatory tests (e.g., quantitative sensory testing) may also be helpful in assessing pain and response to treatment ( ).

Though not diagnostic, neuropathic pain is suspected when certain pain descriptors are used (shooting, electric, burning, tingling, pricking, itching, cold) and the location of the pain is in a region of sensory disturbance. Although the IASP classification referred to earlier identifies three types of neuropathic pain, in this chapter we focus on the two main types of neuropathic pain that are specific to SCI: at-level and below-level neuropathic pain.

At-Level Neuropathic Pain

At-level neuropathic pain refers to pain that occurs in a segmental or dermatomal pattern within the dermatome at the level of neurological injury and three dermatomes below this level ( ) ( Fig. 68-1 ). This type of pain is also referred to as segmental, transitional zone, border zone, end zone, and girdle zone pain, names that reflect its characteristic location in the dermatomes close to the level of injury. It is often associated with allodynia or hyperesthesia of the affected dermatomes.

At-level neuropathic pain may be due to damage to either nerve roots or the spinal cord itself. Pain arising from nerve root damage is typically unilateral and suggested by characteristics such as increased pain in relation to spinal movement. The pain may be due to direct damage to the nerve root during the initial injury or be secondary to spinal column instability and impingement by facet or disc material. Electromyographic or somatosensory evoked potential abnormalities may be present. Diagnosis is assisted by radiographic evidence of compression of the nerve root in the foramen that correlates with the location of the pain.

In the past, pain that occurs at the level of the lesion and that has features of nerve root pain has often been classified as radicular even in the absence of definitive evidence of nerve root damage. However, segmental neuropathic pain may occur in the absence of nerve root damage and may be due to spinal cord rather than nerve root pathology. Animal models of SCI that have damage confined to the spinal cord without root involvement exhibit pain behavior that is similar to that seen in people with at-level neuropathic pain ( ). Although this type of pain may be difficult to distinguish from nerve root pain on the basis of descriptors, such distinction is important because the underlying mechanisms and therefore treatment may be different.

Syringomyelia must always be considered in patients with delayed onset of segmental pain, especially when it is associated with a rising level of sensory loss. Loss of pain and temperature sensation is typical, but all sensory and motor functions can be affected. reported that 65% of a group of paraplegics who had a delayed onset of pain exhibited a syrinx, with the average onset being 6 years following the initial spinal injury. Patients describe a constant, burning pain that may be associated with allodynia or hyperalgesia. The diagnosis is established by magnetic resonance imaging.

An important variant of at-level neuropathic pain is seen after injury to the cauda equina. Even though pain caused by damage to the cauda equina may occur in a diffuse distribution in the lower limbs, it is classified as at-level neuropathic pain because it is due to nerve root damage. Cauda equina pain is reported in the lower lumbar and sacral dermatomes and is usually described as burning, stabbing, and hot. It is constant but may fluctuate with activity or autonomic activation.

Below-Level Neuropathic Pain

Below-level neuropathic pain is also referred to as central dysesthesia syndrome, central pain, phantom pain, or deafferentation pain. It is spontaneous and/or evoked pain that is often diffusely caudal to the level of SCI. It is defined as neuropathic pain and occurs in the region more than three dermatomes below the neurological level of injury ( ) ( Fig. 68-2 ). Sudden noises or jarring movements may trigger this type of pain. Differences in the nature of below-level neuropathic pain may be apparent in those with complete and incomplete lesions. Both complete and partial injuries may be associated with the diffuse, burning pain that appears to be related to spinothalamic tract damage. However, incomplete injuries are more likely to have an allodynic component because of sparing of tracts conveying touch sensation.

Peripheral Mechanisms

Damage to bony spinal structures may result in impingement of nerve roots entering the spinal cord. This may lead to the generation of impulses within primary afferents and the production of radicular at-level neuropathic pain in a similar manner to other peripheral neuropathic pain conditions involving nerve root trauma. The inflammatory process associated with SCI leads to the release of multiple agents, such as nerve growth factor, that can activate and sensitize nociceptive sensory fibers projecting to areas of damage.

Spinal Mechanisms

At least some cases of at-level neuropathic pain appear to be dependent on the presence of a “spinal generator” rather than just nerve root trauma. This is supported by animal research suggesting that at-level neuropathic pain is dependent on preservation of the superficial dorsal horn ( ) and human studies demonstrating that specific ablation of structures in the superficial dorsal horn can provide pain relief ( ). Several case reports of intrathecally administered local anesthetic in people with SCI pain also describe complete (though temporary) abolition of pain when the sensory blockade is above the level of injury ( ).

This ability of spinal local anesthetic to relieve neuropathic pain following SCI led to the proposition of an “irritated focus,” “neural pain generator,” or “spinal generator” located at the distal end of the spinal cord proximal to the injury. This proposition has been supported by a case report in which electrophysiological recordings demonstrated abnormal spontaneous neuronal activity in cells just above the level of injury in a man with upper lumbar SCI ( ). Studies using quantitative sensory testing also demonstrate an association between at-level neuronal hyperexcitability and at-level neuropathic pain, although it is difficult to determine the precise location of the hyperexcitable neurons with this approach ( ).

These clinical observations have also been supported, to some extent, by subsequent investigations using animal models of SCI pain. In an early animal study, found abnormal spontaneous activity in the spinal cord close to the level of injury. Several animal models of neuropathic SCI pain have been developed over the years, including complete or partial cord transection ( ), irradiation ( ), excitotoxic intraspinal injections of quisqualate ( ), and contusion ( ). Though not identical, these models all result in varying but similar behavioral features suggestive of neuropathic pain, including increased sensitivity to mechanical and thermal stimulation and over-grooming. These behavioral changes suggestive of pain and hyperesthesia occur predominantly, though not exclusively, in the dermatomes close to the level of SCI. Importantly, animals in which these models are used display behavioral features of at-level neuropathic pain even when histological examination reveals no evidence of nerve root damage ( ). Thus, with at-level neuropathic pain, both spinal and peripheral pain mechanisms should be considered.

The physiological and biochemical changes underlying such behavior have also been investigated in several animal models. Electrophysiological recordings from spinal cord neurons demonstrate increased responsiveness to peripheral stimuli, an increase in the level of background neuronal activity, and an increased duration of afterdischarge responses following cessation of a stimulus ( ). It has been suggested that the changes in neuronal responsiveness described may be due to damage to the normal inhibitory processes in the spinal cord involving opioids, monoamines, γ-aminobutyric acid (GABA), and glycine.

Trauma to the spinal cord results in an injury cascade that includes excitotoxic, neurochemical, inflammatory, and anatomical components that may contribute to the development of pain ( ). This injury cascade may affect inhibitory neurons and thus the production and release of inhibitory neurotransmitters. Much of the focus in research has been on interference in GABAergic inhibition, and several studies have provided evidence that neuropathic pain is linked to GABAergic dysfunction within the spinal cord close to the site of injury ( ). These changes may underlie a reduction in GABAergic inhibitory tone and lead to amplification of ascending input.

It has also been proposed that pain may be due to an increase in glutamatergic excitatory activity at N -methyl- d -aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors. Ultimately, excitatory factors are thought to activate intracellular signaling cascades that are associated with neuronal sensitization ( ). Up-regulation of the tetrodotoxin-sensitive sodium channel Na _v 1.3 in second-order dorsal horn sensory neurons may also contribute to neuronal hyperexcitability and pain ( ).

Besides pharmacological and functional changes, spinal cord trauma may also result in anatomical or morphological changes that produce pain. Following SCI, several changes take place that appear to reflect attempts at anatomical reorganization in the spinal cord, including structural remodeling of the terminals of primary afferents within the dorsal horn (Christensen and Hulsebosch 1997, ). SCI also results in activation of microglia, which has been linked to the development of below-level neuropathic pain (see Chapter 4 ) ( ).