Involvement of central cannabinoid CB2 receptor in reducing mechanical allodynia in a mouse model of neuropathic pain

We sought to examine the involvement of central cannabinoid CB2 receptor activation in modulating mechanical allodynia in a mouse model of neuropathic pain. JWH133 was demonstrated to be a selective cannabinoid CB2 receptor agonist in mice, reducing forskolin-stimulated cAMP production in CHO cells...

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Bibliographic Details
Published in:	European journal of pharmacology Vol. 583; no. 1; pp. 56 - 61
Main Authors:	YAMAMOTO, Watam, MIKAMI, Tadayoshi, IWAMURA, Hiroyuki
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier 31-03-2008
Subjects:	Animals Biological and medical sciences Cannabinoids - administration & dosage Cannabinoids - pharmacology CHO Cells Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction Cricetinae Cricetulus Cyclic AMP - biosynthesis Female Genetic Vectors Indicators and Reagents Injections, Intraperitoneal Injections, Spinal Ligation Male Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Nervous system (semeiology, syndromes) Neurology Pain - drug therapy Pain - etiology Peripheral Nervous System Diseases - complications Pharmacology. Drug treatments Physical Stimulation Receptor, Cannabinoid, CB2 - agonists Receptor, Cannabinoid, CB2 - genetics Receptor, Cannabinoid, CB2 - physiology Sciatic Nerve - pathology Sciatic Neuropathy - pathology Transfection Allodynia Animal model Nervous system diseases JWH133 Rodentia Central nervous system CB2 cannabinoid receptor Neuropathic pain Cannabinoid CB2 receptor Vertebrata Mammalia Mouse Neuralgia Neurological disorder
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Summary:	We sought to examine the involvement of central cannabinoid CB2 receptor activation in modulating mechanical allodynia in a mouse model of neuropathic pain. JWH133 was demonstrated to be a selective cannabinoid CB2 receptor agonist in mice, reducing forskolin-stimulated cAMP production in CHO cells expressing mouse cannabinoid CB2 and cannabinoid CB1 receptors with EC50 values of 63 nM and 2500 nM, respectively. Intrathecal administration of JWH133 (50 and 100 nmol/mouse) significantly reversed partial sciatic nerve ligation-induced mechanical allodynia in mice at 0.5 h after administration. In contrast, systemic (intraperitoneal) or local (injected to the dorsal surface of the hindpaw) administration of JWH133 (100 nmol/mouse) was ineffective. Furthermore, the analgesic effects of intrathecal JWH133 (100 nmol/mouse) were absent in cannabinoid CB2 receptor knockout mice. These results suggest that the activation of central, but not peripheral, cannabinoid CB2 receptors play an important role in reducing mechanical allodynia in a mouse model of neuropathic pain.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-2999 1879-0712
DOI:	10.1016/j.ejphar.2008.01.010