The antinociceptive effects of fluoxetine

Shaul Schreiber, Maria M. Backer, Ronit Weizman, Chaim G. Pick

Research output: Contribution to journalArticlepeer-review


The authors conducted a study in order to evaluate the analgesic effects of fluoxetine and its interaction with various opioid receptor subtypes. Male ICR mice were tested with the hotplate analgesia meter. The antinociceptive effect was measured following s.c., i.p., i.t. or i.c.v. injection of fluoxetine and opioid agonists. Fluoxetine induced an antinociceptive effect in the hotplate assay. Following s.c., i.t. or i.c.v. injection, fluoxetine elicited an antinociceptive effect in a dose-dependent manner. Intraperitoneal injection of fluoxetine was almost inactive. Naloxone 10 mg/kg, s.c. did not abolish the fluoxetine antinociceptive effect. When administered together with various agonists of opioid receptors, fluoxetine at an inactive dose, induced a statistically significant potentiation of the δ-opioid receptor subtype, κ1-subtype and κ3-subtype (P < 0.005). The potentiation of the μ-opioid receptor did not reach a statistical significance. Fluoxetine alone induces an antinociceptive effect if administered s.c., i.t. or i.c.v. Its effect is not antagonized by naloxone, hence indicating that fluoxetine antinociceptive effects are mediated by a non-opioid mechanism of action. When administered together with opiates, fluoxetine significantly potentiates analgesia at the δ, κ1 and κ3 opioid receptor subtypes, and to a lesser extent, at μ-opioid receptors. These results suggest a potential role for fluoxetine in the management of pain either alone or co-administered with other drugs.

Original languageEnglish
Pages (from-to)349-356
Number of pages8
JournalPain Clinic
Issue number3
StatePublished - 1996


  • 5-HT receptors
  • Analgesia
  • Antidepressants
  • Antinociceptive effect
  • Hotplate assay
  • Opioid receptors
  • Pain
  • Serotonin selective reuptake inhibitors


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