Abstract
This study analyzed the effect of intra-ventrolateral periaqueductal grey (VL PAG) cannabinoid receptor (CB) stimulation on pain responses and rostral ventromedial medulla (RVM) neural activity in the chronic constriction injury (CCI) model of neuropathic pain in rats. Interaction between CB1 and metabotropic glutamate 1 and 5 (mGlu1/mGlu5) receptors was also investigated together with the expression of the CB1 receptor associated Gai3 and cannabinoid receptor interacting 1a (CRIP 1a) proteins and the endocannabinoid synthesising and hydrolysing enzymes.
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, cannabinoid recepors, metabotropic glutamate receptors, periaqueductal grey, ON and OFF cell, neuropathic pain, gray-rostral ventromedical medulla pathway, RVM, microinjections, RT-PCR, Western blot, Immunochemistry
CNS & Neurological Disorders - Drug Targets
Title: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
Volume: 11 Issue: 2
Author(s): Enza Palazzo, Livio Luongo, Giulia Bellini, Francesca Guida, Ida Marabese, Serena Boccella, Francesca Rossi, Sabatino Maione and Vito de Novellis
Affiliation:
Keywords: Cronic constriction injury, cannabinoid recepors, metabotropic glutamate receptors, periaqueductal grey, ON and OFF cell, neuropathic pain, gray-rostral ventromedical medulla pathway, RVM, microinjections, RT-PCR, Western blot, Immunochemistry
Abstract: This study analyzed the effect of intra-ventrolateral periaqueductal grey (VL PAG) cannabinoid receptor (CB) stimulation on pain responses and rostral ventromedial medulla (RVM) neural activity in the chronic constriction injury (CCI) model of neuropathic pain in rats. Interaction between CB1 and metabotropic glutamate 1 and 5 (mGlu1/mGlu5) receptors was also investigated together with the expression of the CB1 receptor associated Gai3 and cannabinoid receptor interacting 1a (CRIP 1a) proteins and the endocannabinoid synthesising and hydrolysing enzymes.
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.
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Palazzo Enza, Luongo Livio, Bellini Giulia, Guida Francesca, Marabese Ida, Boccella Serena, Rossi Francesca, Maione Sabatino and de Novellis Vito, 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, CNS & Neurological Disorders - Drug Targets 2012; 11 (2) . https://dx.doi.org/10.2174/187152712800269731
DOI https://dx.doi.org/10.2174/187152712800269731 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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