Similarly, experiments with rodents (Behrmann et al., 1994) and cats (Faden et al., 1981) have demonstrated that thyrotropin-releasing hormone (TRH) can significantly improve long-term motor recovery after a spinal cord injury. However, a large-scale randomized clinical trial designed to examine the effects of TRH analogs in individuals with acute spinal cord injuries was not fully completed (Pitts et al., 1995), and such an evaluation has not been revisited.
Chronic pain, one of the most common sequelae of spinal cord injuries, is not adequately controlled by currently available treatments. Inadequately controlled pain not only erodes quality of life, functioning, and mood but also can lead to depression and, most tragically, suicide (Hulsebosch, 2003; Finnerup and Jensen, 2004). Some clinicians have been slow to recognize that chronic pain is real, has serious consequences, and should not be dismissed as grounds for psychiatric referral (Hulsebosch, 2003).
To assist with the development of treatments for the chronic pain associated with spinal cord injuries, an International Association for the Study of Pain task force was formed to define distinct categories and sources of pain (Vierck et al., 2000). Two categories were defined: at-level neuropathic pain and below-level neuropathic pain. At-level neuropathic pain is correlated to the amount of damage to the gray matter above and below the primary injury site (Yezierski, 2000) and the amount of secondary cellular damage caused by the release of neurotransmitters (glutamate and N-methyl-D-aspartate [NMDA]) (Tator and Fehlings, 1991) and inflammatory cytokines (Bethea et al., 1998; Vierck et al., 2000). Below-level neuropathic pain is associated with axonal disruption, loss, or damage along the spinothalamic tract (Bowsher, 1996).
Experts in spinal cord injury-associated pain consider the development of pain therapies to be a major and feasible research priority, considering the body of research that has been amassed over the past 10 years about pain mechanisms in individuals with spinal cord injuries, as well as related research on other forms of neuropathic pain. Neuropathic pain, as explained in Chapter 2, results from direct damage to neural tissue, whereas nociceptive pain is caused by damage to nonneural tissues (bone, muscles, and ligaments). Nociceptive pain is what most healthy people are familiar with, and it is more treatable and controllable with standard pain therapies like anti-inflammatory agents and analgesics. Neuropathic pain is often treated with antidepressants and anticonvulsants, but their efficacies spe-