On the antinociceptive effect of fluoxetine, a selective serotonin reuptake inhibitor.
Antidepressant drugs are reported to be used as co-analgesics in clinical management of migraine and neuropathic pain. The mechanism through which they alleviate pain remains unknown. The present study explores the possible mechanism of a selective serotonin reuptake inhibitor (SSRI) fluoxetine-induced antinociception in animals. Acetic acid-induced writhing, hot plate and tail-flick test were used to assess fluoxetine-induced antinociception. Fluoxetine (5-20 mg kg(-1), i.p.) produced a significant and dose-dependent antinociceptive effect against acetic acid-induced writhing in mice. Fluoxetine (20 mg kg(-1)) also exhibited antinociceptive effect in tail flick as well as hot plate assays. Further, i.c.v. administration of fluoxetine showed significant antinociception against writhing test in rats. However, fluoxetine (1 microg/10 microl/rat, i.c.v.) did not exhibit any antinociceptive effect in serotonin-depleted animals. Further, pindolol (10 mg kg(-1), i.p.) enhanced fluoxetine-induced antinociceptive effect. The antinociceptive effect of fluoxetine was sensitive to blockade by naloxone (5 mg kg(-1), i.p.) and naltrexone (5 mg kg(-1), i.p.). These data suggest that fluoxetine-induced antinociception involves both central opioid and the serotoninergic pathways.
Singh
V P
VP
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, 160 014, Chandigarh, India.
Jain
N K
NK
Kulkarni
S K
SK
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D005473:Fluoxetine; D009020:Morphine; D017367:Selective Serotonin Reuptake Inhibitors