Open AccessHistamine Modulation of Acute Nociception Involves Regulation of Na v 1.8 in Primary Afferent Neurons in Mice
Author(s) -
Yu Jie,
Fang Qi,
Lou GuoDong,
Shou WenTing,
Yue JiaXing,
Tang YingYing,
Hou WeiWei,
Xu TianLe,
Ohtsu Hiroshi,
Zhang ShiHong,
Chen Zhong
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12134
Subject(s) - histidine decarboxylase , histamine , nociception , stimulation , chemistry , neuroscience , endogeny , endocrinology , noxious stimulus , medicine , histamine h3 receptor , histaminergic , premovement neuronal activity , pharmacology , biology , receptor , histidine , biochemistry , enzyme , antagonist
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. Na v 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 α‐fluoromethylhistidine (α‐ FMH ), a specific HDC inhibitor, or feeding mice a low‐histamine diet also enhanced nociception in the wild‐types. Na v 1.8 expression in primary afferent neurons was increased both in HDC −/− and in α‐ FMH ‐treated wild‐type mice. A higher Na v 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. Na v 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 Na v 1.8 expression and the excitability of nociceptive primary afferent neurons may be involved in the underlying mechanisms.