Antihistamine antinociception is mediated by Gi-protein activation

Neuroscience
N GaleottiA Bartolini

Abstract

The effect of the i.c.v. administration of antisense oligodeoxynucleotides directed against the alpha subunit of different Gi-proteins (anti-Gi alpha(1), anti-Gi alpha(2), anti-Gi alpha(3)) on the antinociception induced by the H(1)-antihistamines was evaluated in the mouse hot-plate test. The administration of diphenhydramine (20 mg kg(-1) s.c.), pyrilamine (15 mg kg(-1) s.c.) and promethazine (6 mg kg(-1) s.c.) produced an increase of the pain threshold which peaked 15 min after injection. Pretreatment with anti-Gi alpha(1) (12.5 microg per mouse i.c.v.), anti-Gi alpha(2) (25 microg per mouse i.c.v.) and anti-Gi alpha(3) (25 microg per mouse i.c.v.), administered 24 and 18 h before test, prevented the antihistamine-induced antinociception. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous motility and inspection activity, as revealed by the hole board test. These results suggest an important role played by the Gi-protein pathway in the transduction mechanism involved in the enhancement of the pain threshold produced by H(1)-antihistamines.

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Citations

Nov 15, 2003·Neuroscience·N GaleottiC Ghelardini
Jul 21, 2004·The Journal of Experimental Medicine·Irina G StavrovskayaBruce S Kristal
Nov 5, 2008·The Journal of Experimental Medicine·Xiaoyu LiHarald von Boehmer
Feb 1, 2014·Physiology & Behavior·M E RiverosF Torrealba
Feb 24, 2015·European Journal of Pharmacology·Jann-Inn TzengJhi-Joung Wang
Nov 11, 2016·Canadian Journal of Physiology and Pharmacology·Mario I Ortiz

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