Nerve fibers and endometriotic lesions: partners in crime in inflicting pains in women with endometriosis.

One of major objectives in treating endometriosis is to alleviate pain since dysmenorrhea and other types of pain top the list of complaints from women with endometriosis who seek medical attention. Indeed, endometriosis-associated pain (EAP) is the most debilitating of the disease that negatively impacts on the quality of life in affected women, contributing significantly to the burden of disease and adding to the substantial personal and societal costs. Unfortunately, the mechanisms underlying the EAP are still poorly understood. In the last two decades, one active research field in endometriosis is the investigation on the distribution and genesis of nerve fibers in eutopic and ectopic endometrium, and the attempt to use endometrial nerve fiber density for diagnostic purpose. Since EAP presumably starts with the terminal sensory nerves, in or around endometriotic lesions, that transduce noxious mediators to the central nervous system (CNS) which ultimately perceives pain, this field of research holds the promise to elucidate the molecular mechanisms underlying the EAP, thus opening new avenues for novel diagnostics and therapeutics. In this review, we shall first briefly provide some basic facts on nerve fibers, and then provide an overview of some major findings in this filed while also note some conflicting results and expose areas in need of further research. We point out that since recently accumulated evidence suggests that endometriotic lesions are wounds undergoing repeated tissue injury and repair, the relationship between endometriotic lesions and nerve fibers is not simply unidirectional, i.e. lesions promote hyperinnervations. Rather, it is bidirectional, i.e. endometriotic lesions and nerve fibers engage active cross-talks, resulting in the development of endometriosis and pain. That is, nerve fibers and endometriotic lesions are actually partners in crime in inflicting pains in women with endometriosis, aided and abetted possibly by other culprits, some yet to be identified. We provide a list of possible perpetrators likely to be involved in this crime. Finally, we discuss possible implications when viewing the relationship from this vista.