2004 Volume 11 Issue 4 Pages 387-396
In order to study the participation of histamine in pain perception, histamine-related gene knockout (KO) mice were examined for pain threshold by means of several nociceptive tasks. H1 receptor KO (H1RKO) mice showed significantly fewer nociceptive responses to the hot-plate, tail-flick, tail-pressure, paw-withdrawal, formalin, capsaicin, and abdominal constriction tests. Sensitivity to noxious stimuli in H1RKO mice were significantly decreased when compared to wild-type mice. The antinociceptive phenotypes of H2 receptor KO (H2RKO) were similar to H1RKO mice. We also examined the antinociceptive effects of morphine in H1RKO and H2RKO mice. In the nociceptive assays, the antinociceptive effects produced by morphine were more enhanced in both H1RKO and H2RKO mice. The effects of histamine H1 and H2 receptor antagonists on morphine-induced antinociception were studied in ICR mice. The co-administrations of d-chlorpheniramine or cimetidine enhanced the effects of morphine in all nociceptive assays examined. The histidine decarboxylase gene knockout mice showed similar phenotypes of H1RKO and H2RKO mice. These results suggest that histamine play a suppressive role in morphine-induced antinociception in the spinal and supra-spinal levels through H1 and H2 receptors.