GW406381, a novel COX-2 inhibitor, attenuates spontaneous ectopic discharge in sural nerves of rats following chronic constriction injury
| Autor: | Fei-Yue Zhao, Alison J Reeve, Iain P. Chessell, David Spanswick, Jo C Martindale |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Nitrogen Action Potentials Constriction Pathologic Hydrocarbons Aromatic Rats Sprague-Dawley Lactones Sural Nerve medicine Animals Sulfones Rofecoxib Pain Measurement Cyclooxygenase 2 Inhibitors Dose-Response Relationship Drug business.industry Nerve Compression Syndromes Nerve injury medicine.disease Rats Pyridazines Anesthesiology and Pain Medicine Allodynia Peripheral neuropathy Neurology Hyperalgesia Anesthesia Chronic Disease Peripheral nerve injury Neuropathic pain Pyrazoles COX-2 inhibitor Neurology (clinical) medicine.symptom business medicine.drug |
| Zdroj: | Pain. 128:78-87 |
| ISSN: | 0304-3959 |
| Popis: | There are several lines of evidence to suggest that cyclooxygenase-2 (COX-2) plays an important role in the generation and maintenance of neuropathic pain states following peripheral nerve injury. However, COX-2 inhibitors are generally ineffective in reversing mechanical allodynia and hyperalgesia in models of neuropathic hypersensitivity. Here, we have investigated the effects of GW406381, a novel COX-2 inhibitor, on mechanical allodynia, hyperalgesia and generation of spontaneous ectopic discharge in rats following chronic constriction injury (CCI) of the sciatic nerve and compared it with rofecoxib. GW406381 (5mg/kg, 5 days of treatment) significantly reversed the CCI-induced decrease in paw withdrawal thresholds (PWTs), assessed using both von Frey hair and paw pressure tests, whereas an equi-effective dose of rofecoxib (5mg/kg, 5 days of treatment) in inflammatory pain models was ineffective. In rats treated with GW406381, the proportion of fibres showing spontaneous activity was significantly lower (15.58%) than that in the vehicle (32.67%)- and rofecoxib (39.66%)-treated rats. Ibuprofen, a non-selective COX inhibitor, at 5mg/kg, orally dosed three times a day for 5 days did not significantly affect the PWTs in CCI rats. In naïve rats, GW406381 did not significantly change the PWTs. These results illustrate that COX-2 may indeed play an important role in the maintenance of neuropathic pain following nerve injury, but that only certain COX-2 inhibitors, such as GW406381, are effective in this paradigm. Whilst the mechanisms underlying this differential effect of GW406381 are not clear, differences in drug/enzyme kinetic interactions may be a key contributing factor. |
| Databáze: | OpenAIRE |
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