Kappa-opioid receptor modulation of the release of substance P in the dorsal horn.
Substance P (SP), a member of the tachykinin peptide family, has been found in high concentrations in the superficial laminae of the dorsal horn and it is thought to play a major role in the transmission of nociceptive information. Dynorphin(1-8), an opioid peptide with high selectivity for the kappa-opioid receptor subtype, is also found in the dorsal horn of the spinal cord. The aim of this study was to determine the effect of dynorphin(1-8) on the release of SP-like-immunoreactivity (SPLI) in the dorsal horn before and during the activation of peripheral nociceptors by a thermal stimulus. A push-pull canula was used to perfuse the dorsal horn of non-anesthetized decerebrate/spinal transected rats and the collected perfusates were assayed for SPLI by using radioimmunoassay. Dynorphin(1-8) applied to the spinal cord at a concentration of 1 microM elicited a 27 +/- 8% decrease in the basal release of SPLI and prevented the increase in the release of SPLI evoked by the application of a noxious thermal stimulus to the ipsilateral hind paw and lower limb. The effect of dynorphin(1-8) was reversed by 2 microM of nor-binaltorphimine (nor-BNI), a selective kappa opioid receptor antagonist. Application of nor-BNI alone to the perfusate resulted in a 62 +/- 23% increase in the basal release of SPLI. In conclusion, dynorphin(1-8) reduces the basal release of SPLI and prevents the increase in the release of SPLI elicited by the application of a noxious cutaneous thermal stimulus. This effect is mediated through the kappa-opioid receptor, which appears to tonically regulate the release of SPLI in the dorsal horn.
Zachariou
V
V
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-7605, USA.
Goldstein
B D
BD
D000818:Animals; D001481:Basal Metabolism; D004399:Dynorphins / Q000494:pharmacology*; D006614:Hindlimb; D006358:Hot Temperature; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*
D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D017473:Receptors, Opioid, kappa; C016116:substance P-like peptides; D013373:Substance P; D004399:Dynorphins; C026770:dynorphin (1-8)