| First Author | Yu J | Year | 2013 |
| Journal | CNS Neurosci Ther | Volume | 19 |
| Issue | 9 | Pages | 649-58 |
| PubMed ID | 23773488 | Mgi Jnum | J:324644 |
| Mgi Id | MGI:6840381 | Doi | 10.1111/cns.12134 |
| Citation | Yu J, et al. (2013) Histamine modulation of acute nociception involves regulation of Nav 1.8 in primary afferent neurons in mice. CNS Neurosci Ther 19(9):649-58 |
| abstractText | 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. Nav 1.8 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 alpha-fluoromethylhistidine (alpha-FMH), a specific HDC inhibitor, or feeding mice a low-histamine diet also enhanced nociception in the wild-types. Nav 1.8 expression in primary afferent neurons was increased both in HDC(-/-) and in alpha-FMH-treated wild-type mice. A higher Nav 1.8 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. Nav 1.8 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 Nav 1.8 expression and the excitability of nociceptive primary afferent neurons may be involved in the underlying mechanisms. |
