Histamine modulation of acute nociception involves regulation of Nav 1.8 in primary afferent neurons in mice.
CNS Neurosci Ther
; 19(9): 649-58, 2013 Sep.
Article
in En
| MEDLINE
| ID: mdl-23773488
ABSTRACT
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 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.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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histamine
/
Nociception
/
NAV1.8 Voltage-Gated Sodium Channel
/
Neurons, Afferent
Limits:
Animals
Language:
En
Journal:
CNS Neurosci Ther
Journal subject:
NEUROLOGIA
/
TERAPEUTICA
Year:
2013
Document type:
Article
Affiliation country:
China