Excitotoxic injury to thoracolumbar gray matter alters sympathetic activation and thermal pain sensitivity.

Studies of humans, monkeys and rodents have implicated combined gray and white matter damage as important for development of chronic pain following spinal cord injury (SCI). Below-level chronic pain and hyperalgesia following injury to the spinal white matter, including the spinothalamic tract (STT), can be enhanced by excitotoxic influences within the gray matter at the site of SCI. Also, excitotoxic injury of thoracic gray matter without interruption of the STT results in below-level heat hyperalgesia. The present study evaluates the possibility that thoracolumbar gray matter injury increases sensitivity to nociceptive heat stimulation by altering spinal sympathetic outflow. Thermal preferences of rats for heat (45 °C) versus cold (15 °C) were evaluated before and after thoracolumbar injections of quisqualic acid (QUIS). A pre-injury preference for heat changed to a post-injury preference for cold. Systemic activation of the sympathetic nervous system by restraint stress decreased the heat preference pre-injury and increased the cold preference post-injury. The heat aversive effect of stress was magnified and prolonged post-injury, compared to pre-injury. Also, peripheral sympathetic activation by nociceptive stimulation was evaluated pre- and post-injury by measuring thermal transfer through a hindpaw during stimulation with 44.5 °C. Skin temperature recordings revealed enhanced sympathetic activation by nociceptive heat stimulation following spinal QUIS injury. However, increased sympathetic activation with peripheral vasoconstriction should enhance cold aversion, in contrast to the observed increase in heat aversion. Thus, peripheral sympathetic vasoconstriction can be ruled out as a mechanism for heat hyperalgesia following excitotoxic gray matter injury.

Evaluation of the pathologic characteristics of excitotoxic spinal cord injury with MR imaging.

BACKGROUND AND PURPOSE: Although high-resolution MR imaging is a valuable diagnostic tool, in vivo MR imaging has not yet been compared with in vitro MR imaging and histologic techniques following experimental spinal cord injury (SCI). The goal of the present study was to evaluate the feasibility of using in vivo MR imaging, in vitro MR imaging, and histologic techniques to study pathologic changes associated with excitotoxic SCI at a single time point. These results are important for future research using in vivo MR imaging to study the temporal profile of pathologic changes following SCI. METHODS: Rats received intraspinal injections of quisqualic acid at the T12-L2 spinal level. In vivo T1- and T2-weighted and dynamic contrast-enhanced MR images were collected 17-24 days postinjury. Once completed, spinal cords were removed and in vitro MR microscopy and histologic assessment were performed. MR images were collected using 4.7-T (in vivo) and 14.1-T magnets (in vitro). RESULTS: Pathologic changes--including hemorrhage, neuronal loss, cavities, and central canal expansion--were visible in T2-weighted in vivo MR images. Evaluation of the blood-spinal cord barrier after injury with contrast agent enhancement showed no disruption at the time points evaluated. In vitro MR images and histologic evaluation confirmed pathologic details observed in vivo. CONCLUSION: Results show that high-resolution in vivo MR imaging has the potential to be used in studying the progression of pathologic changes at multiple time points following SCI. This strategy may provide a way of studying structure-function relationships between therapeutic interventions and different pathologic characteristics of the injured spinal cord.