Antinociceptive effects of fluoxetine in a mouse model of anxiety/depression

Pain was reported by 60-90% of patients with depression, and chronic pain states are often linked to depression. Animal models of pain/depression are generally lacking for the identification of centrally active drugs. In the present study, pain sensitivity was assessed in a mouse model of anxiety/depression on the basis of chronic corticosterone (CORT) administration through the drinking water (CORT model). We measured thermal hyperalgesia as shown by a decrease in the latency to hind paw licking in the hot plate test and cold allodynia reflected by a decrease in the time spent on the plate set at 20°C in the thermal preference plate test. Subsequently, we determined the effect of chronic administration of the selective serotonin reuptake inhibitor fluoxetine (an antidepressant known to reverse anxiety/depressive-like state in CORT-treated mice) on pain relief. Fluoxetine administration reduced both heat hyperalgesia and cold allodynia, thus unveiling a putative link between mood and nociception in the CORT model. This hypothesis is consistent with previous clinical studies reporting the analgesic efficacy of fluoxetine in depressed patients suffering from pain disorders. Together, these results suggest that the CORT model, with pain/anxiety/depressive-like state, is a good candidate for translational research.