EVIDENCE FOR HYPERNOCICEPTION INDUCTION FOLLOWING HISTAMINE H-1 RECEPTOR ACTIVATION IN RODENTS

To characterize the mechanism of the analgesic action of H-1 antihista minics the effects of a new, highly selective agonist, 2-(3-trifluorom ethylphenyl)histamine dihydrogenmaleate (FMPH), and of the better know n H-1 agonist, 2-thiazolylethylamine (2-TEA), were studied on pain thr eshold by means of three different kinds of tests for nociception (mou se hot plate and abdominal constriction, and rat paw pressure tests). Low doses of both substances (2.65 and 6.5 mu g/animal i.c.v. for FMPH in the hot plate and paw pressure tests, and 0.3 mu g/rat i.c.v. for 2-TEA in the paw pressure test) were slightly but significantly hypern ociceptive. The selective H-1 receptor antagonist, pyrilamine maleate (10-30 mg/kg s.c.), induced a dose-dependent antinociception in all th ree tests, and both FMPH and 2-TEA prevented its effect, but not that of morphine, thus indicating action on Ill receptors. The same low dos es of FMPH were also able to enhance animals' spontaneous motility and curiosity. High doses of FMPH (13.23-132.3 mu g/mouse i.c.v.) raised the pain threshold, but due to the severe motor impairment evidenced b y the rota rod test, this cannot be considered as real antinociception . An increase in the pain threshold lacking any motor impairment was o bserved for tenfold higher doses of 2-TEA (3 and 10 mu g/mouse i.c.v.) . This may be due to action on H-2 receptors, with the reported relati ve potency of 2-TEA for H-1 and H-2 receptors being about 12:1. It is therefore suggested that H-1 receptor activation increases sensitivity to noxious stimuli.