The ENDO model displays pain symptoms like those occurring in women with endometriosis. produce a variety of individual differences in pain that can, in some women, become independent SLRR4A of the disease itself. == CONCLUSIONS == Major advances in improving understanding and alleviating pain in endometriosis will likely occur if the focus changes from lesions to pain. In turn, how endometriosis affects the CNS would be best examined in the context of mechanisms underlying other chronic pain conditions. Keywords:endometriosis, chronic pelvic pain, central nervous system sensitization, pathophysiology, neurovascular == Introduction == Endometriosis is an estrogen-dependent inflammatory disease that occurs in women of reproductive age, and generally becomes inactive with menopause, unless a woman uses post-menopausal hormone therapy (Goodmanet al., 1989;Takayamaet al., 1998;Missmeret al., 2004;Cumiskeyet al., 2008). The epidemiologic association between endometriosis and chronic pelvic pain (CPP) is suggested by the observation that among women who undergo laparoscopy, endometriosis is found in one-third who undergo surgery for CPP, compared with only 5% of those who do not have infertility or CPP (Howard, 1993,2009). CPP often debilitates women with endometriosis for years (Sinaiiet al., 2007), has a high risk of emergency department visits (Gaoet al., 2006), and is associated with time lost from work and significant physical and social debility (Simoenset al., 2007). Additional expenses in women with endometriosis-related pain can arise from comorbid pain conditions like painful bladder syndrome (formerly called interstitial cystitis), migraine and irritable bowel syndrome (Mirkinet al., 2007). Gynecologists and patients believe that CPP associated with endometriosis is caused by the endometriosis lesions (Fauconnier and Chapron, Dapansutrile 2005). Establishing how the lesions do so has proved difficult. The spectrum of pains and lesions contributes to this challenge. Although analgesics, hormonal therapies and surgeries have been the mainstay of therapy, pain often returns, and return of pain is not necessarily associated with the return of lesions. A fundamental concept is that the experience of pain is due to activity in the central nervous system (CNS). Thus, the relationship between pain and endometriosis could benefit by being reconsidered in the context of the nervous system. The purpose of this review, therefore, is to summarize the translational research that has recently exploded on this issue and to identify future directions. == Methods == An electronic database search (Pubmed, Medline and Embase) was performed to identify basic and clinical studies concerned with mechanisms of pain in women with endometriosis from the earliest date available, usually 1967. Mesh terms used included endometriosis, chronic pain, CPP, sensory nerve fibers, autonomic nerve fibers, sympathetic, estradiol, pelvic pain, innervation, sensitization, medical treatments including treatments by specific names, surgical treatments, including treatments by specific names and for specific sections like the reproductive tract, additional mesh terms were added. Mesh terms were used in various combinations and usually included the terms chronic pain AND endometriosis. Few studies reviewed and included in the manuscript address this relationship. Most are studies of endometriosis pathophysiology or treatment. Thus, the review is not a formal systematic literature overview, nor were quantitative analyses carried out. Instead, the authors synthesize and interpret the existing basic, clinical and translational research regarding the association between endometriosis and pain. == Spectrum of pain and lesions == The constellation of pain symptoms associated with endometriosis varies from person to person. Symptoms encompass an unspecified combination of dysmenorrhea, dyspareunia and non-menstrual chronic pelvicabdominal muscle pain with the sentinel symptom being dysmenorrhea (TableI). Non-menstrual CPP may persist for much of the month or only during specific times, such as at ovulation. Some women have additional painful symptoms such as dysuria, dyschezia and other chronic musculoskeletal conditions, which may or Dapansutrile Dapansutrile may not be related to endometriosis. These pain Dapansutrile symptoms and their chronicity, patterns in relation to the menstrual Dapansutrile cycle and association with other types of visceral pain, ultimately reflect changing actions of the nervous system. == Table I. == Spectrum of pains and endometriosis lesions. Laparoscopic surgery has enabled surgical diagnosis of endometriosis by confirming the existence of lesions and transformed its surgical treatment (Kennedyet al., 2005). The appearance and location of endometriosis lesions, like the symptoms of pain, vary from person to person. On gross inspection, endometriosis is subdivided.