Investigation into the Role of P2x(3)/P2x(2/3) Receptors in Neuropathic Pain Following Chronic Constriction Injury in the Rat: an Electrophysiological Study.
From: Pain Department, Neurology and GI CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW. Caroline.J.Sharp@gsk.com
British journal of pharmacology
- Publish Date: Jul 2006
- ISSN: 0007-1188
- Volume: 148
- Issue: 6
- Pages: 845-52
- Medium: Print
- Language: English
- Citation (JAMA): Sharp Caroline J, Reeve Alison J, Collins Sue D, et al. Investigation into the Role of P2x(3)/P2x(2/3) Receptors in Neuropathic Pain Following Chronic Constriction Injury in the Rat: an Electrophysiological Study.. Br. J. Pharmacol. Jul 2006;148:845-52
Abstract
1. Two P2X(3)/P2X(2/3) receptor antagonists with different potencies were profiled electrophysiologically in a rat model of nerve injury. 2. A-317491 has poor CNS penetrance (blood:brain, 1:<0.05), and was therefore administered intravenously in chronic constriction injury (CCI)- and sham-operated rats to study the involvement of P2X(3) subunit-containing receptors in the periphery in neuropathic pain. A-317491 and Compound A were administered topically to the spinal cord to investigate the central contribution. 3. There were no significant inhibitory effects of A-317491 intravenous (i.v.) seen in sham-operated animals compared to vehicle controls. In CCI-operated animals, there were significant inhibitory effects of 3 mg kg(-1) A-317491 i.v. on C fibre-evoked responses, and with 10 mg kg(-1) A-317491 i.v. on A delta and C fibre-evoked responses. No significant effects of A-317491 were observed after topical application to the spinal cord. In contrast, when Compound A was administered spinally in CCI animals, there was a decrease in A delta and C fibre-evoked responses, and wind up. 4. These changes indicate that A-317491 has a selective effect on neuronal responses in CCI animals compared to sham, demonstrating an increased involvement of P2X(3)/P2X(2/3) receptors in sensory signalling following nerve injury. In addition, the more potent antagonist Compound A was effective spinally, unmasking a potential central role of P2X(3)/P2X(2/3) receptors at this site post nerve injury. These data support a role for P2X(3)/P2X(2/3) antagonists in the modulation of neuropathic pain.
Mesh Headings (Keywords): Animals, Constriction, Pathologic, Evoked Potentials, Male, Nerve Fibers, Unmyelinated, Neuralgia, Phenols, Polycyclic Compounds, Rats, Receptors, Purinergic P2, Spinal Cord
Check for Full Text / PubMed Unique Identifier (PMID): 16770326
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