Opioid peptide messenger RNA expression is increased at spinal and supraspinal levels following excitotoxic spinal cord injury

Spinal cord injury in rats is known to cause anatomical, physiological and molecular changes within the spinal cord. These changes may account for beh avioral syndromes that appear following spinal cord injury, syndromes belie ved to be related to the clinical condition of chronic pain. Intraspinal in jection of quisqualic acid produces an excitotoxic injury with pathological characteristics similar to those associated with ischemic and traumatic sp inal cord injury. In addition, recent studies have demonstrated changes in blood flow, neuronal excitability and gene expression in the brain followin g excitotoxic injury, indicating that behavioral changes may result from mo dification of neuronal substrates at supraspinal levels of the neuraxis. Be cause changes in spinal opioid peptide expression have been demonstrated in models of traumatic spinal cord injury and chronic pain, the present study investigated messenger RNA expression of the opioid peptides, preproenkeph alin and preprodynorphin, at spinal and supraspinal levels following excito toxic spinal cord injury. Male, Long-Evans rats were given three intraspina l injections of quisqualic acid (total 1.2 mu l, 125 mM). After one, three, five, seven or 10 days, animals were killed and quantitative in situ hybri dization performed on regions of the spinal cord surrounding the lesion sit e, as well as whole-brain sections through various levels of the thalamus. Preproenkephalin and preprodynorphin expression was increased in spinal cor d areas adjacent to the site of quisqualic injection and in cortical region s associated with nociceptive function, preproenkephalin in the cingulate c ortex and preprodynorphin in the parietal cortex, both ipsilaterally and co ntralaterally at various time-points following injury. These results further our knowledge of the secondary events that occur foll owing spinal cord injury, specifically implicating supraspinal opioid syste ms in the CNS response to spinal cord injury. (C) 2000 IBRO. Published by E lsevier Science Ltd. All rights reserved.