CP/CPPS is frequently diagnosed in the adult male population with prevalence going up to 25%. Major CP/CPPS symptoms include chronic pelvic or perineal pain, common urological symptomatology and erectile dysfunction. In the base of this syndrome stands apyrogenic inflammation of prostate. The prolonged and progressive chronic pain and peripheral inflammation experienced by these patients leads to brain-related comorbidities such depression and multiple disabilities. Although numerous studies have shown that these brain-related comorbidities, primarily depression, contribute to reduced quality of life in CP/CPPS patients, the exact mechanism of this association, as well as adequate strategies for psychosocial treatment of affected individuals, have yet to be developed. Therefore, mechanisms of depression development in inflammatory and pain syndromes, including CP/CPPS, will be discussed in this chapter with particular focus on the role of cytokines as mediator of neuroinflammation, alterations in the hippocampal neurogenesis, and contribution of gliotransmitters from astrocytes.