Role of histamine H(1) receptor in pain perception: a study of the receptor gene knockout mice

Eur J Pharmacol. 2000 Mar 10;391(1-2):81-9. doi: 10.1016/s0014-2999(00)00060-1.


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 Adelta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Capsaicin
  • Chlorpheniramine / chemistry
  • Chlorpheniramine / pharmacology
  • Formaldehyde
  • Histamine H1 Antagonists / chemistry
  • Histamine H1 Antagonists / metabolism
  • Histamine H1 Antagonists / pharmacology
  • Hot Temperature
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Pain / chemically induced
  • Pain / prevention & control
  • Pain Measurement / drug effects
  • Pain Threshold / drug effects*
  • Physical Stimulation
  • Pyrilamine / metabolism
  • Reaction Time / drug effects
  • Receptors, Histamine H1 / drug effects*
  • Receptors, Histamine H1 / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stereoisomerism


  • Histamine H1 Antagonists
  • Receptors, Histamine H1
  • Formaldehyde
  • Chlorpheniramine
  • Pyrilamine
  • Capsaicin