Enhanced antinociception by intrathecally-administered morphine in histamine H1 receptor gene knockout mice

Jalal Izadi Mobarakeh, Shinobu Sakurada, Takafumi Hayashi, Tohru Orito, Kaori Okuyama, Tsukasa Sakurada, Atsuo Kuramasu, Takehiko Watanabe, Takeshi Watanabe, Kazuhiko Yanai

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


We previously reported that histamine H1 receptor gene knockout mice (H1KO) showed lower spontaneous nociceptive threshold to pain stimuli when compared to wild-type mice. The objective of the present study was to examine the antinociceptive effect of intrathecally-administered morphine in H1KO mice. The antinociceptive effects of morphine were examined using assays for thermal (tail-flick, hot-plate, paw-withdrawal), mechanical (tail-pressure) and chemical nociception (formalin and capsaicin tests) using H1KO and wild-type mice. In these nociceptive assays, intrathecally-administered morphine produced significant antinociceptive effects in wild-type mice. The antinociceptive effect produced by intrathecally administered morphine was enhanced in the knockout mice. We also examined the effect of an histamine H1 receptor antagonist, an active (d-) isomer of chlorpheniramine, on morphine-induced antinociception in ICR mice. The intrathecal co-administration of d-chlorpheniramine enhanced the effect of morphine in all nociceptive assays examined. The pharmacological experiments using d-chlorpheniramine further substantiate the evidence for the histamine H1 receptor-mediated suppression of morphine-induced antinociception. These results suggest that existing H1 receptors play an inhibitory role in morphine-induced antinociception at the spinal cord level.

Original languageEnglish
Pages (from-to)1079-1088
Number of pages10
Issue number8
Publication statusPublished - 2002


  • Antinociception
  • Histamine H antagonist
  • Histamine H receptors
  • Intrathecal injection
  • Knockout mice
  • Morphine

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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