In the present study, we used three depression-pain comorbidity animal models (genetic predisposition, chronic social stress, arthritis) to examine the hypothesis that the 5-HT1A auto-receptor is critical for the reduced antidepressant and antihyperalgesic effects of fluoxetine through upregulation of IDO1 expression in the DRN. The gene discussed is IDO1; the disease is Arthritis.