How does chronic psychosocial distress induce pain? Focus on neuroinflammation and neuroplasticity changes.

Chronic primary pain including fibromyalgia for the musculoskeletal system persists for more than 3 months. Its etiological factors and the pathophysiological mechanisms are not known, and therefore, there is no satisfactory therapy, it is an unmet medical need condition. The only etiological and aggravating factor is chronic psychosocial distress, which is known to cause neuroimmune and endocrine changes both in the periphery and the central nervous system. In this short review, we introduce our research perspective by summarizing the recent literature on the interactions between chronic pain, stress, and commonly co-morbid mood disorders. Immune activation, autoimmunity, neuro-immune-vascular crosstalks and neuroinflammation play roles in the pathophysiology of these conditions. Data on stress-induced neuroplasticity changes at cellular and molecular levels were also collected in relation to chronic primary pain both from clinical studies and animal experiments of translational relevance. Understanding these mechanisms could help to identify novel therapeutic targets for chronic primary pain including fibromyalgia.