Neuroendocrine and neuroimmune mechanisms underlying comorbidity of pain and obesity

Pain and obesity, as well as their associated impairments, are major health concerns. Understanding the relationship between the two is the focus of a growing body of research. However, early researches attribute increased mechanical stress from excessive weight as the main factor of obesity-related pain, which not only over-simplify the association, but also fail to explain some controversial outcomes arising from clinical investigations. This review focuses on neuroendocrine and neuroimmune modulators importantly involved in both pain and obesity, analyzing nociceptive and anti-nociceptive mechanisms based on neuroendocrine pathways including galanin, ghrelin, leptin and their interactions with other neuropeptides and hormone systems which have been reported to play roles in pain and obesity. Mechanisms of immune activities and metabolic alterations are also discussed, due to their intense interactions with neuroendocrine system and crucial roles in the development and maintenance of inflammatory and neuropathic pain. These findings have implications for health given rising rates of obesity and pain-related diagnoses, by providing novel weight-control and analgesic therapies targeted on specific pathways.