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 mu M 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 mu M 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.