Kappa-opioid receptor modulation of the release of substance P in the dorsal horn

Abstract

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 κ-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 μM 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 μM 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 κ-opioid receptor, which appears to tonically regulate the release of SPLI in the dorsal horn.