A dual effect of 5-HT 1B receptor stimulation on nociceptive dorsal horn neurones in rats

Abstract

In this study the modulatory effects of 5-HT 1B receptor activation on wide dynamic range neurones in the spinal cord were studied. Extracellular single unit recordings of dorsal horn neurones were performed in intact urethane-anaesthetized female Sprague–Dawley rats, and the receptive field distally on one hind paw was electrically stimulated with needle electrodes applied to the skin. The 5-HT 1B receptor agonist, CP-93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one), the 5-HT 1A/B receptor antagonist cyanopindolol, and the 5-HT 1A receptor antagonist WAY100635 ( N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride), were applied directly onto the spinal cord, and single unit responses were counted separately for A β-, A δ-, C-fibre responses and post-discharge according to the latencies. A dual effect of CP-93,129 was observed: 50 nmol CP-93,129 caused a clear inhibition of the A δ-fibre responses, whereas 50 and 150 nmol CP-93,129 produced a dose-dependent increase in post-discharge without affecting A β- and C-fibre responses. Application of 50 nmol cyanopindolol or 50 nmol WAY100635 alone did not affect neither the neuronal A-fibre nor the C-fibre responses, but when 50 nmol cyanopindolol was coadministered with 50 nmol CP-93,129 the effect of CP-93,129 alone was blocked: the A δ-fibre response was not inhibited and the post-discharge was not increased. In contrast, 50 nmol WAY100635 did not block the effect of 50 nmol CP-93,129 when the two drugs were coadministered. These results suggest that stimulation of the 5-HT 1B receptors may have both pro- and antinociceptive effects on wide dynamic range neurones in the dorsal horn after repeated electrical stimulation.