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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chaves, C. T. Francischi, J. N. Lima, A. S. Rocha, O. A. Ferreira-alves, D. L. Moura, A. C. L. Bakhle, Y. S. |
| Description | Author Affiliation: Francischi JN ( Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Brazil. janettif@icb.ufmg.br) |
| Abstract | 1. It is well-established that inhibitors of cyclo-oxygenase (COX) and hence of prostaglandin (PG) biosynthesis reverse inflammatory hyperalgesia and oedema in both human and animal models of inflammatory pain. 2. Paw oedema and hyperalgesia in rats were induced by injecting carrageenan (250 micro g paw(-1)) into a hindpaw. Both inflammatory responses were followed for 24 h after the injection, measuring hyperalgesia by decreased pain threshold in the paws and oedema by plethysmography. 3. Three selective inhibitors of cyclo-oxygenase-2 (COX-2), celecoxib, rofecoxib and SC 236, given systemically in a range of doses, before the inflammatory stimulus, abolished carrageenan-induced hyperalgesia with little reduction of oedema. These inhibitors also induced hypoalgesia, increasing nociceptive thresholds in the inflamed paw above normal, non-inflamed levels. This hypoalgesia was lost at the higher doses of the selective inhibitors, although hyperalgesia was still prevented. 4. In paws injected with saline only, celecoxib, given at the dose inducing the maximum hypoalgesia after carrageenan, did not alter the nociceptive thresholds. 5. Two non-selective inhibitors of COX-2, indomethacin and piroxicam, abolished hyperalgesia and reduced oedema but did not induce hypoalgesia. 6. Celecoxib given locally into the paw also abolished inflammatory hyperalgesia and induced hypoalgesia without reducing oedema. 7. We conclude that hypoalgesia is expressed only over a critical range of COX-2 inhibition and that concomitant inhibition of COX-1 prevents expression of hypoalgesia, although hyperalgesia is still prevented. 8 Our results suggest a novel anti-nociceptive pathway mediating hypoalgesia, involving COX-2 selectively and having a clear peripheral component. This peripheral component can be further explored for therapeutic purposes. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 137 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2002-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Cyclooxygenase Inhibitors Pharmacology Hyperalgesia Prevention & Control Inflammation Isoenzymes Drug Effects Prostaglandin-Endoperoxide Synthases Animals Carrageenan Celecoxib Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Dose-Response Relationship, Drug Edema Chemically Induced Hindlimb Indomethacin Lactones Pain Threshold Piroxicam Pyrazoles Sulfonamides Sulfones Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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