Central effects of histamine H-receptor agonists and antagonists on nociception in the rat.

The effects of intracerebroventricular injection of histamine H-receptor agonists (4-methylhistamine, 4-MeH; dimaprit, DIM), H-antagonists (cimetidine, CIM; ranitidine, RAN; famotidine, FAM) and of the DIM chemical analogue SK&F 91487 on hot-plate latency in rats were examined. Both DIM (0.4-0.8 μmol/rat) and 4-MeH (0.4-0.8 μmol/rat) significantly enhanced the pain threshold, whereas SF&F 91487 (0.8 μmol/rat) had no effect, indicating that DIM antinociception is specifically due to its activity on histamine (HA) receptors. The H-antagonists CIM (0.8 μmol/rat) and RAN (0.6 μmol/rat) also enhanced the pain threshold, while FAM (0.03 μmol/rat) did not modify pain latency. When injected before 4-MeH, FAM reduced the antinociceptive effect of 4-MeH. These findings suggest that the antinociceptive activity of CIM and RAN is not related to specific blockade of H-receptors and that the activation of HA-H-receptors is inhibitory to nociception. [ABSTRACT FROM AUTHOR]