Excitotoxic
spinal cord injury (SCI) causes anatomic, physiologic and molecular changes within the spinal cord and brain.
Intraspinal injection of
quisqualic acid (QUIS) produces an excitotoxic injury that leads to the onset of behavioral syndromes, believed to be related to the clinical condition of
chronic pain. The
opioid system, classically involved in the suppression of
pain transmission, has been associated with the onset of
pain-related behaviors and changes in spinal
opioid peptide expression have been demonstrated in various models of SCI and
chronic pain. Recently, changes in
opioid peptide expression have been demonstrated in both spinal and supraspinal areas following excitotoxic SCI. Therefore, the purpose of this study was to examine changes in
opioid peptide gene expression as they relate to the onset of
pain behaviors following excitotoxic SCI. Male, Long-Evans rats were given an
intraspinal injection of 1.2 microl of 125 mM QUIS and allowed to survive for 10 days, a duration sufficient for the development of
pain-related behaviors. Animals were assessed daily for the presence of excessive grooming behavior, i.e. self-directed biting and scratching resulting in damage to superficial and deeper layers of the skin. Animals were also tested for thermal
hypersensitivity using a cold plate apparatus on days 5, 7, and 10 following QUIS injection. After sacrifice, quantitative in situ hybridization was performed on regions of the spinal cord surrounding the lesion site as well as whole brain sections through various levels of the thalamus and cortex. Spinal
preproenkephalin (PPE) and
preprodynorphin (
PPD) expression was significantly increased in animals that developed excessive grooming behaviors vs. those that did not. For PPE, this difference was seen bilaterally, in areas of cord caudal to the site of injury. For
PPD, this difference was seen only ipsilateral to the site of injection, rostral to the site of injury. In addition, PPE expression in the anterior cingulate cortex and
PPD expression in the contralateral parietal cortex were significantly higher in grooming vs. non-grooming animals. These results support previous conclusions that both spinal and supraspinal regulation of endogenous
opioid peptide expression plays a role in the response to or onset of post-SCI
pain. These results also suggest that the
opioid peptides are regulated independently and serve different functions in response to SCI.