Targeting endogenous analgesia systems for endometriosis treatment

Endometriosis is a chronic inflammatory disease that affects 1 in 10 women of childbearing age. It is characterized by the growth of endometrium in extrauterine locations and is associated with chronic pelvic pain, infertility, emotional distress and loss of working ability. Current clinical management provides unsatisfactory outcomes. Thus, the development of more effective therapeutic strategies is still an unmet clinical need, and their development relies on the establishment of animal models that recapitulate the features of endometriosis. The present Thesis has characterized a surgical model of endometriosis that shows nociceptive, affective-like behaviors and impaired cognition, reproducing the symptoms observed in endometriosis patients. In this model of endometriosis, natural cannabinoids alleviate nociceptive behaviors, restore cognitive function and inhibit the development of endometriotic growths. A kappa opioid receptor agonist also shows pain-relieving properties in this model, although affective and cognitive disturbances persist regardless of the pain alleviation. A minimally invasive model of endometriosis that also mimics the symptoms of human endometriosis revealed that minimal endometriosis leads to neuroinflammation in the central nervous system.