In vivo evidence for multiple opiate receptors mediating analgesia in the rat spinal cord.

In rats implanted with chronic catheters in the spinal subarachnoid space, intrathecal injections of SKF 10047 and dynorphin did not produce any elevation of the nociceptive threshold as defined by hot-plate and tail-flick tests. In contrast, intrathecal ethylketocyclazocine (EKC) and (D-Ala2,D-Leu5)-enkephalin (DADL) administration resulted in a dose-dependent antinociceptive effect which was reversible with intraperitoneal naloxone. Calculation of the Schild dose-ratio plots for the data derived from systemically administered naloxone reveals a slope of--1 and a calculated pA2 value of 6.8 for EKC and 6.2 for DADL. Also, animals made tolerant to systemic morphine showed a diminished analgesic response to intrathecal morphine and EKC when compared to naive animals. There was, however, no significant change in the dose response curve of intrathecal DADL. Thus, these experiments suggest that in addition to mu receptors a separate subpopulation of delta but not kappa or sigma receptors are involved with spinally mediated analgesia.