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The analgesic actions of centrally administered celecoxib are mediated by endogenous opioids
- Source :
- Pain. 142:94-100
- Publication Year :
- 2009
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2009.
-
Abstract
- Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) and blocks prostaglandin (PG) biosynthesis associated with inflammatory conditions. In a model of peripherally induced inflammatory pain in rats, celecoxib, given systemically, induced a state of hypoalgesia where the nociceptive threshold was raised above basal values, an effect not observed after treatment with non-selective inhibitors of COX (indomethacin, piroxicam). Here, we have assessed the possibility that these atypical effects of celecoxib could be mediated by action at a site in the CNS. Inflammation and hyperalgesia were induced in one hind paw of rats by intraplantar injection of carrageenan (250microg). Nociceptive thresholds to mechanical stimulation were measured in the inflammed and contralateral paws for 6h after carrageenan injection. Celecoxib, SC236 (selective COX-2 inhibitors), indomethacin (non-selective COX inhibitor), SC560 (selective COX-1 inhibitor) or morphine were given by i.c.v. injection, 30 min before carrageenan. Celecoxib, SC236 or morphine-induced hypoalgesia whereas, after indomethacin or SC 560, the nociceptive threshold only returned to basal values. Naltrexone, also given i.c.v., reversed the hypoalgesia after celecoxib or morphine. Bestatin, an inhibitor of metabolism of endogenous opioid peptides, given i.c.v., potentiated the analgesic effects of a low dose of celecoxib. Taken together, these data indicate that celecoxib could act centrally after systemic administration to produce its characteristic profile of analgesia in this model of peripheral inflammatory pain. Moreover, this atypical analgesia appeared to be mediated by endogenous opioids rather than by inhibition of PG biosynthesis.
- Subjects :
- Male
Pain Threshold
Time Factors
Narcotic Antagonists
Analgesic
Pain
Pharmacology
Carrageenan
Piroxicam
Drug Administration Schedule
Leucine
Reaction Time
medicine
Animals
Immunologic Factors
Drug Interactions
Enzyme Inhibitors
Opioid peptide
Injections, Intraventricular
Pain Measurement
Endogenous opioid
Inflammation
Analysis of Variance
Sulfonamides
Hypoalgesia
Dose-Response Relationship, Drug
Morphine
business.industry
Drug Administration Routes
Anti-Inflammatory Agents, Non-Steroidal
Naltrexone
Rats
Analgesics, Opioid
Anesthesiology and Pain Medicine
Neurology
Celecoxib
Hyperalgesia
Pyrazoles
Neurology (clinical)
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 03043959
- Volume :
- 142
- Database :
- OpenAIRE
- Journal :
- Pain
- Accession number :
- edsair.doi.dedup.....3aab8fb8fa0be0a50d2cdc834aba469b