Histamine modulation of acute nociception involves regulation of nav1.8 in primary afferent neurons in mice

Jie Yu, Qi Fang, Guo Dong Lou, Wen Ting Shou, Jia Xing Yue, Ying Ying Tang, Wei Wei Hou, Tian Le Xu, Hiroshi Ohtsu, Shi Hong Zhang, Zhong Chen

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Summary: Aims: To explore the role of histamine in acute pain perception and its possible mechanisms. Methods: Pain-like behaviors induced by four types of noxious stimuli (hot-plate, tail-pressure, acetic acid, and formalin) were accessed in mice. Nav1.8 expression and functions in primary afferent neurons were compared between histidine decarboxylase knockout (HDC-/-) mice and their wild-types. Results: HDC-/- mice, lacking in endogenous histamine, showed elevated sensitivity to all these noxious stimuli, as compared with the wild-types. In addition, a depletion of endogenous histamine with α-fluoromethylhistidine (α-FMH), a specific HDC inhibitor, or feeding mice a low-histamine diet also enhanced nociception in the wild-types. Nav1.8 expression in primary afferent neurons was increased both in HDC-/- and in α-FMH-treated wild-type mice. A higher Nav1.8 current density, a lower action potential (AP) threshold, and a higher firing rate in response to suprathreshold stimulation were observed in nociception-related small DRG neurons of HDC-/- mice. Nav1.8 inhibitor A-803467, but not TTX, diminished the hyperexcitability and blocked repetitive AP firing of these neurons. Conclusion: Our results indicate that histamine participates in acute pain modulation in a dose-related manner. The regulation of Nav1.8 expression and the excitability of nociceptive primary afferent neurons may be involved in the underlying mechanisms.

Original languageEnglish
Pages (from-to)649-658
Number of pages10
JournalCNS Neuroscience and Therapeutics
Issue number9
Publication statusPublished - 2013 Sep


  • Dorsal root ganglion
  • Histamine
  • Hyperexcitability
  • Na1.8

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)


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