Possible involvement of opioidergic systems in the antinociceptive effect of the selective serotonin reuptake inhibitors in sciatic nerve-injured mice.
The involvement of opioid receptor activation in the antinociceptive effect of either fluvoxamine, a selective serotonin reuptake inhibitor, or serotonin (5-HT) on thermal hyperalgesia and mechanical allodynia in a model of neuropathic pain in mice induced by sciatic nerve ligation was examined. The experiments were conducted 2 or 6 weeks after unilateral sciatic nerve ligation. Ipsilateral thermal hyperalgesia and mechanical allodynia were observed both 2 and 6 weeks after sciatic nerve ligation. Neither s.c. fluvoxamine nor i.t. 5-HT affected sciatic nerve ligation-induced thermal hyperalgesia or mechanical allodynia in mice 2 weeks after sciatic nerve ligation. However, the same dose of either fluvoxamine or 5-HT significantly reduced mechanical allodynia but not thermal hyperalgesia in sciatic nerve ligated mice 6 weeks after surgery. The antinociceptive effect of fluvoxamine on sciatic nerve ligation-induced mechanical allodynia in mice 6 weeks after surgery was completely abolished by pretreatment with either naloxone, a nonselective opioid receptor antagonist, or beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, pretreatment with naltrindole, a selective delta-opioid receptor antagonist, partially but significantly inhibited the antinociceptive effect of fluvoxamine in sciatic nerve ligated mice at the 6th postoperative week. The antinociceptive effect induced by i.t. 5-HT was also completely antagonized by either naloxone or beta-funaltrexamine, and partially inhibited by naltrindole. However, pretreatment with nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no effect against either s.c. fluvoxamine- or i.t. 5-HT-induced antinociception. These results suggest that the antinociceptive effect of s.c. fluvoxamine or i.t. 5-HT in the chronic state of sciatic nerve ligation-induced neuropathic pain may be related to opioidergic activity, mainly through the activation of spinal mu- and delta-opioid receptors.
Nozaki
Chihiro
C
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan.
Kamei
Junzo
J
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D016666:Fluvoxamine / Q000494:pharmacology*; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control; D007278:Injections, Spinal; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D009437:Neuralgia / Q000503:physiopathology / Q000517:prevention & control*; D017294:Ondansetron / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries / Q000503:physiopathology* / Q000601:surgery; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors
D000700:Analgesics; D016666:Fluvoxamine; D007650:Ketanserin; D009270:Naloxone; D009292:Narcotic Antagonists; D017294:Ondansetron; D011957:Receptors, Opioid; D012701:Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors