Kappa opioid receptor agonists differentially inhibit two classes of rat spinal neurons excited by colorectal distention

Quantitative neurophysiological studies have identified the presence of at least 2 spinal neuronal populations (abrupt and sustained) that are excited by the noxious visceral stimulus colorectal distention. This study examined the effects of the kappa opioid receptor agonists fedotozine and U50488H on the activity of these neurons.

In decerebrate, cervical spinal cord-transected male rats, the lumbosacral spinal cord was exposed by a laminectomy. Dorsal horn neurons showing excitatory responses to colorectal distention (80 mm Hg, 20 seconds) were identified using microelectrodes. Cumulative doses of fedotozine and U50488H were administered intravenously or intrathecally, and antagonists were used.

Intravenous fedotozine and U50488H dose-dependently inhibited the evoked activity of sustained neurons. This inhibition was partially reversed by the kappa opioid antagonist norbinaltorphimine. The same agents had insignificant effects on the evoked activity of abrupt neurons. Fedotozine inhibited spontaneous activity of both abrupt and sustained neurons. Intrathecally administered U50488H had no effect on abrupt or sustained neurons, but intrathecally administered fedotozine inhibited the evoked and spontaneous activity of both groups.

Kappa opioid receptor agonists acting peripherally had differential effects on 2 spinal neuronal populations responsive to colorectal distention. Fedotozine had additional inhibitory effects acting within the spinal cord.