Changes in Cannabinoid Receptor Subtype 1 Activity and Interaction with Metabotropic Glutamate Subtype 5 Receptors in the Periaqueductal Gray-Rostral Ventromedial Medulla Pathway in a Rodent Neuropathic Pain Model
In rats not subjected to CCI-induced pain, intra-VL PAG (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) (2-4-8 nmol), a CB receptor agonist, increased the tail flick latency and changed the ongoing activity of RVM OFF and the tail flick-related activity of the ON and OFF cells, accordingly. These effects were prevented by SR141716A and MPEP, selective CB1 and mGlu5 receptor antagonists, respectively, though not by CPCCOEt, a selective mGlu1 receptor antagonist. A higher dose up to 16 nmol of WIN 55,212-2 was necessary to increase tail flick latency and change ON and OFF cell activity in CCI rats. Consistently, CCI rats showed a decrease in the expression of CB1 receptors, NAPE-PLD, Gαi3 and CRIP 1a proteins;the expression of diacylglycerol lipase A (DAGLA) was increased while fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL) did not change. As in control rats, MPEP and SR141716A also blocked WIN 55,212-2- induced effects in CCI rats. These data demonstrate a down regulation of the endocannabinoid system and a functional interaction between mGlu5 and CB1 receptors for cannabinoid-mediated effect in the PAG-RVM pain circuitry in neuropathic pain inflicted rats.
Keywords: Cronic constriction injury; Immunochemistry; ON and OFF cell; RT-PCR; RVM; Western blot; cannabinoid recepors; gray-rostral ventromedical medulla pathway; metabotropic glutamate receptors; microinjections; neuropathic pain; periaqueductal grey
Document Type: Research Article
Affiliations: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy.
Publication date: 2012-03-01
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