Involvement of H₁ receptors in the central antinociceptive effect of histamine: Pharmacological dissection by electrophysiological analysis

Abstract

Intracerebroventricular (i.c.v.) administration of histamine (HA, 0.025–0.1 μM/rat) to arthritic rats induces a dose-related inhibition of the neuronal thalamic firing evoked by peripheral noxious stimuli. To characterize the type(s) of HA receptors involved in this depressing activity of the amine we used electrophysiological techniques to examine the effects of i.c.v. administration of H₁ and H₂ agonists and antagonists on the spontaneous and evoked nociceptive firing of the thalamic neurons in rats rendered arthritic by Freund's adjuvant. The H₁ agonist 2-pyridylethylamine (0.4–1.0 μM/rat, i.c.v) displayed a dose-dependent antinociceptive effect very similar to that of HA, while the H₂ agonist dimaprit (0.05–0.2 μM/rat, i.c.v.) did not modify thalamic firing. Neither mepyramine (H₁ antagonist, 0.1 μM/rat, i.c.v.) nor zolantidine (H₂ antagonist, 0.01 μM/rat, i.c.v.) modified the evoked firing of rat thalamic neurons. When administered before HA (0.1 μM/rat, i.c.v.) mepyramine but not zolantidine was able to inhibit the antinociceptive effect of HA. On the basis of the present electrophysiological results, we suggest that a specific interaction of histamine with H₁ receptors may be important for its antinociceptive effect on afferent peripheral inputs to the thalamus.