The role of purinergic P2X3 receptors and endometriosis-associated hyperalgesia

Endometriosis is a chronic gynecological condition characterized by endometrial tissue outside the uterine cavity. Recent research has focused on the relationship between the purinergic system and endometriosis. As a purinergic system component, extracellular adenosine triphosphate (ATP) has been involved as a crucial mediator of chronic pain associated with the disease, as well as P2X3 receptors, which play a key role in sensitization of nerve fibers and generation of nociceptive, neuropathic, and inflammatory pain. In addition, ectonucleotidases such as CD39 and CD73, which regulate ATP hydrolysis, have an altered expression in endometriotic lesions, contributing to extracellular ATP accumulation, intensifying inflammation and pain. Together, immune cells and their product are increased in endometriotic foci and promote the emergence of new lesions through their contribution to retrograde menstruation. Some studies have observed significant changes in mitochondrial respiration, notably decreased oxygen consumption in the affected endometrium. These various cellular processes that are mediated by ATP and adenosine in the uterine cavity and exert effects on immune defense will be herein reviewed in detail to investigate possible inhibitors, their activity, and potential exploration of the purinergic pathway as a therapeutic alternative.