Depression is often associated with local and/or systemic diseases. Chronic inflammation, pain and depression are a clinical triad increasingly recognized as co-morbid. Peripheral and central inflammation can alter neuronal activity, thereby contributing to the psych emotional and somatic symptoms of depression. Preliminary evidence suggests that mast cells direct the immune pathways mediating this triad. Chronic pelvic pain in women could be a paradigm of the triad, and of considerable clinical relevance.