| Autor: |
Caroline J, Sharp, Alison J, Reeve, Sue D, Collins, Jo C, Martindale, Scott G, Summerfield, Becky S, Sargent, Simon T, Bate, Iain P, Chessell |
| Rok vydání: |
2006 |
| Předmět: |
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| Zdroj: |
British journal of pharmacology. 148(6) |
| ISSN: |
0007-1188 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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