The effects of the selective serotonin reuptake inhibitor fluoxetine in somatic and visceral nociception in mice

Abstract

Introduction: Experimental research on fluoxetine potent antinociceptive effects and it’s interactions with various opioid and adrenergic receptor derivatives, in cutaneous and visceral pain models were investigated. Material and method: The experiment was carried out, with white mice (20-25g), divided into 7 groups of 7 animals each, treated orally with the same volume of solution, for 7 days, as follows: Group I: distilled water 0,3ml (DW); Group II (M): metamyzole 10mg/kbw; Group III (FLX-10): fluoxetine 10mg/kbw; Group IV (FLX-30): fluoxetine 30mg/kbw; Group V (FLX+ATN): fluoxetine 30mg/kbw+atenolol lm g/kbw ; Group VI (FLX+TLZ): fluoxetine 30mg/kbw+tolazolin lm g/kbw, Group VII (NLX+FLX): naloxone 5mg/kbw+fluoxetine 30mg/kbw. Hot plate was used to asses fluoxetine-induced antinociception. The model of visceral pain consists of writhing test using diluted acetic acid (0,6%). Data were presented as +/- standard deviation and significance was analyzed using SPSS for Windows version 17.0 and ANOVA method. P-values less than 0.05 are considered statistically significant comparing with those of control groups. Experimental protocol was implemented according to recommendations of the Gr.T. Popa University Committee for Research and Ethical Issues. Results and conclusions: Oral administration of fluoxetine (10-30mg/kbw) resulted in a significant and dose-dependent antinociceptive effect in writhing test (p<0,05). Atenolol (1 mg/kbw) association increased this antinociceptive effect. Fluoxetine (30mg/kbw) also exhibited antinociceptive effect in hot plate assay. Furthermore, tolazoline administration antagonized fluoxetine visceral analgesic effect, 15 minutes after chemical noxious peritoneal irritation. Fluoxetine-induced antinociception was significantly inhibited by naloxone, in the interval between 20 minutes to 25 minutes in writhing test. These data suggest that fluoxetine-induced antinociception involves central opioid, adrenergic and serotoninergic pathways.