title: Histamine modulation of acute nociception involves regulation of Nav 1.8 in primary afferent neurons in mice.
abstract: OBJECTIVE
  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 α-fluoromethylhistidine (α-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 α-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Fang
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Lou
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Shou
authors.forename: Jia-Xing
authors.initials: JX
authors.lastname: Yue
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Tang
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hou
authors.forename: Tian-Le
authors.initials: TL
authors.lastname: Xu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Zhang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000200:Action Potentials; D000208:Acute Disease; D000818:Animals; D005727:Ganglia, Spinal / Q000502:physiology; D006632:Histamine / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000502:physiology; D008762:Methylhistidines / Q000494:pharmacology; D051379:Mice; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D059225:Nociception / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D008762:Methylhistidines; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; D013779:Tetrodotoxin; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase
keywords: Dorsal root ganglion; Histamine; Hyperexcitability; Nav1.8