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It seems that histamine release in the site of neuronal injury could contribute to the neuropathic pain mechanism. In the present study, we investigated the anti-allodynic effects of chronic administration of different classes of histamine H1 and H2 receptor antagonists on neuropathic nociceptive behavior following tibial nerve transection (TNT) in rats.Peripheral neuropathy was induced by TNT surgery. We performed acetone tests (AT) to record cold allodynia, Von Frey tests (VFT) to measure mechanical allodynia, double plate test (DPT) to evaluate thermal place preference/avoidance and open field test (OFT) for evaluation of animal activity.TNT rats showed a significant mechanical and cold allodynia compared to the sham group. Chlorpheniramine (5 and 15mg/kg, i.p) significantly attenuated cold allodynia and prevented cold plate avoidance behavior and at the dose of 15mg/kg remarkably decreased mechanical allodynia. Fexofenadine (10 and 30mg/kg, p.o) significantly attenuated the mechanical allodynia and prevented cold plate avoidance. Ranitidine (5 and 15mg/kg, i.p) significantly prevented cold plate avoidance behavior and at the dose of 15mg/kg notably improved mechanical and cold allodynia. Famotidine (1 and 3mg/kg, p.o) was ineffective on all nociceptive tests. Gabapantin (100mg/kg, p.o) significantly improved all types of nociceptive behaviors.These results indicate that both blood brain barrier penetrating (chlorpheniramine) and poorly penetrating (fexofenadine) histamine H1 receptor antagonists could improve the neuropathic pain sign, but only the blood brain barrier penetrating histamine H2 receptor antagonist (ranitidine) could produce anti-allodynic effects in the TNT model of neuropathic pain in rats.