Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model

Abstract

Intraspinal injections of the AMPA-metabotropic receptor agonist quisqualic acid (QUIS) were made in an effort to simulate injury induced elevations of excitatory amino acids (EAAs), a well documented neurochemical change following spinal cord injury (SCI). The progressive pathological sequela associated with QUIS injections closely resembles the cascade of events described following ischemic and traumatic SCI and the pathogenesis of cavities in the clinical condition of post-traumatic syringomyelia. Using different injection parameters, i.e. depth and volume, to deliver QUIS into the cord the results have shown that the technique of intraspinal injection can be used to produce graded patterns of neuronal loss in specific regions of the spinal gray matter. Furthermore, neuronal loss in the dorsal horn, sparing the superficial laminae, results in the onset of spontaneous (excessive grooming behavior) and evoked (mechanical allodynia and thermal hyperalgesia) behaviors commonly associated with experimental models of chronic neuropathic pain. Thus, the present results provide a morphological correlate of spontaneous and evoked pain related behaviors following excitotoxic SCI. The behavioral characteristics combined with the similarities between QUIS induced injury and the clinical pathology of SCI support the use of the excitotoxic model in studies related to the central mechanism(s) of altered sensation, including pain, following spinal injury.