Modification of formalin-induced nociception by different histamine receptor agonists and antagonists

The present study evaluated the effects of different histamine receptor agonists and antagonists on the nociceptive response in the mouse formalin test. Intracerebroventricular (20–40 μg/mouse i.c.v.) or subcutaneous (1–10 mg/kg s.c.) injection of HTMT (H1 receptor agonist) elicited a dose-related hyperalgesia in the early and late phases. Conversely, intraperitoneal (20 and 30 mg/kg i.p.) injection of dexchlorpheniramine (H1 receptor antagonist) was antinociceptive in both phases. At a dose ineffective per se, dexchlorpheniramine (10 mg/kg i.p.) antagonized the hyperalgesia induced by HTMT (40 μg/mouse i.c.v. or 10 mg/kg s.c.). Dimaprit (H2 receptor agonist, 30 mg/kg i.p.) and ranitidine (H2 receptor antagonist, 20 and 40 mg/kg i.p.) reduced the nociceptive responses in the early and late phases. No significant change in the antinociceptive activity was found following the combination of dimaprit (30 mg/kg i.p.) with ranitidine (10 mg/kg i.p.). The antinociceptive effect of dimaprit (30 mg/kg i.p.) was prevented by naloxone (5 mg/kg i.p.) in the early phase or by imetit (H3 receptor agonist, 25 mg/kg i.p.) in both early and late phases. The histamine H3 receptor agonist imetit was hyperalgesic following i.p. administration of 50 mg/kg. Imetit-induced hyperalgesia was completely prevented by treatment with a dose ineffective per se of thioperamide (H3 receptor antagonist, 5 mg/kg i.p.). The results suggest that histamine H1 and H3 receptor activations increase sensitivity to nociceptive stimulus in the formalin test.