Role of histamine H1 receptor in pain perception: a study of the receptor gene knockout mice

Abstract To study the participation of histamine H 1 receptors in pain perception, histamine H 1 receptor knockout mice were examined for pain threshold by means of three different kinds of nociceptive tasks. These included assays for thermal nociception (hot-plate, tail-flick, paw-withdrawal), mechanical nociception (tail-pressure), and chemical nociception (abdominal constriction, formalin test, capsaicin test) which evoked pain by the activation in nociceptive Aδ and C fibers. The mutant mice lacking histamine H 1 receptors 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 histamine H 1 receptor knockout mice significantly decreased when compared to wild-type mice. This data indicates that histamine plays an important role in both somatic and visceral pain perceptions through histamine H 1 receptors. The difference in the effect of histamine H 1 receptors antagonist, the active ( d -) and inactive ( l -) isomers of chlorpheniramine on ICR mice further substantiates the evidence of the role of histamine H 1 receptors on pain threshold.