GW274150, a novel and highly selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), shows analgesic effects in rat models of inflammatory and neuropathic pain
| Autor: | Iain P. Chessell, Sue D. Collins, Richard G. Knowles, Jorge De Alba, Philip Colthup, Nick M. Clayton |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Freund's Adjuvant Analgesic Nitric Oxide Synthase Type II Sulfides Pharmacology Nitric oxide chemistry.chemical_compound Animals Medicine Inflammation Analgesics Dose-Response Relationship Drug biology business.industry Rats Nitric oxide synthase Treatment Outcome Anesthesiology and Pain Medicine Nociception Neurology chemistry Hyperalgesia Freund's adjuvant Anesthesia Neuropathic pain biology.protein Neurology (clinical) Sciatic nerve Nitric Oxide Synthase medicine.symptom business |
| Zdroj: | Pain. 120:170-181 |
| ISSN: | 0304-3959 |
| Popis: | Nitric oxide (NO), synthesised by different isoforms of nitric oxide synthase (NOS), has been linked with the development and maintenance of nociception. We studied the role of the inducible isoform, iNOS, in two different rat pain models with an inflammatory component. iNOS was immunohistochemically detected locally in the paw 6h after Freund's Complete Adjuvant (FCA) injection, showing a plateau at 24-72 h and falling slowly in the following weeks. This correlated with the late phase of the hypersensitivity to pain revealed in the behavioural tests. A highly selective iNOS inhibitor GW274150 (1-30 mg/kg orally, 24h after FCA) suppressed the accumulation of nitrite in the inflamed paw indicating substantial iNOS inhibition. At the same time it partially reversed FCA-induced hypersensitivity to pain and edema in a dose-dependent manner. After Chronic Constriction Injury (CCI) surgery to the sciatic nerve, iNOS presence was only detected locally in the region of the nerve (inflammatory cells). GW274150 (3-30 mg/kg orally, 21 days after surgery) also reversed significantly the CCI-associated hypersensitivity to pain. No iNOS was detectable in dorsal root ganglia, spinal cord or brain in either model. This study demonstrates a role for peripherally-expressed iNOS in pain conditions with an inflammatory component and the potential value of iNOS inhibitors in such conditions. |
| Databáze: | OpenAIRE |
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