Expression of c-fos mRNA is increased and related to dynorphin mRNA expression following excitotoxic spinal cord injury in the rat.
Previous studies have demonstrated that excitotoxic spinal cord injury (SCI) created by the intraspinal injection of quisqualic acid (QUIS) is capable of inducing opioid peptide gene expression within the spinal cord and cortex. The opioids are classically involved in the suppression of pain transmission but specifically, dynorphin, has been implicated in the secondary pathophysiologic response to SCI. Activation of the immediate early gene, c-fos, has been implicated in the induction of preprodynorphin (PPD) gene expression and therefore, may be an important intermediate step in the generation of the opioid response to SCI. The purpose of this study was to investigate whether intraspinal QUIS injection induces c-fos expression within the spinal cord. Male, Long-Evans, adult rats (n=5) received an intraspinal injection of 1.2 microl of 125 mM QUIS directed at spinal segments T12-L2. Four hours post-injection brain and spinal cord tissues were removed and processed for in situ hybridization. Integrated density of c-fos and PPD mRNA expression was increased in the spinal dorsal horn following QUIS injection as compared to sham-injected animals. This indicates that SCI rapidly induces c-fos and PPD expression and suggests that c-fos plays a role in the induction of PPD expression.
Abraham
K E
KE
Division of Physical Therapy, Shenandoah University, Winchester, VA 22601, USA.
Brewer
K L
KL
D000818:Animals; D004399:Dynorphins / Q000235:genetics* / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016318:Quisqualic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C036448:pre-prodynorphin; D004399:Dynorphins; D016318:Quisqualic Acid