Topical review Pain and endometriosis Susan Evans a , Gila Moalem-Taylor b , David J. Tracey b, * a Endometriosis Care Centres Australia, Adelaide, SA 5067, Australia b School of Medical Sciences, University of New South Wales Sydney, NSW 2052, Australia Received 10 May 2007; received in revised form 27 June 2007; accepted 16 July 2007 1. Introduction Endometriosis is the commonest cause of chronic pelvic pain in women (Fauconnier and Chapron, 2005). It is characterized by the presence of uterine endometrial tissue outside of the uterus, most com- monly in the pelvic cavity. The disorder mainly affects women of reproductive age. Symptoms of endometri- osis include recurrent painful periods, painful inter- course, painful defecation during menstruation, chronic lower abdominal pain and hypersensitivity, chronic lower back pain and infertility (Farquhar, 2007). For many women, endometriosis has a negative impact on the ability to work, on family relationships and self-esteem (Huntington and Gilmour, 2005). Many women with endometriosis describe a progres- sion of symptoms over their menstrual life, which may include a mix of different pains and abnormal visceral sensations, indicative of viscero-visceral hyper- algesia and suggestive of neuropathic pain (Horowitz, 2007). Current medical treatments for endometriosis include oral contraceptives, progestogens, androgenic agents, gonadotrophin releasing hormone analogues, as well as laparoscopic surgical excision of the endometriotic lesions. However, management of pain in women with endometriosis is currently insufficient for many women. Here we review the involvement of the nervous system, immune cells and inflammatory response, and hormones in endometriosis as well as current practice in pain management. We suggest that persistent nociceptive input from endometrial tissues might lead not only to peripheral sensitisation, but also to central sensitisation resulting in increased responsiveness of dorsal horn neurons innervated by viscera and somatic tissues. 2. Visceral nociceptors Nociceptors are found in most kinds of tissue, includ- ing the viscera (Cervero and Laird, 1999). However, their existence in viscera including the reproductive organs was disputed for some time. One reason for this was that clinicians found it difficult to elicit pain from internal organs. For example, Lewis said ‘‘The body of the uterus can be cut or burnt; the broad ligaments can be dissected painlessly’’ (Lewis, 1942). It may be that many nociceptors in the internal organs are ‘silent nociceptors’ (Gebhart, 2000). These nociceptors do not normally respond to intense mechanical or thermal stim- uli, but when the surrounding tissue is inflamed, they become sensitised and will respond to stimuli such as pressure, distension or heat. This means that some noci- ceptors may only respond to stimuli when tissue pathol- ogy is present. For example, a normal appendix can be cut without causing pain, but becomes painful when tis- sue pathology is present. It is no longer in doubt that nociceptors are present in the viscera, including the reproductive organs, and there is good evidence that nociceptors are present in the uterus and cervix. This evidence is based on electrophysiological recordings (Berkley et al., 1988; Berkley et al., 1990) and immuno- cytochemical labelling of substance P and calcitonin gene-related peptide in uterine nerve fibres (Tong et al., 2006). 0304-3959/$32.00 Ó 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2007.07.006 * Corresponding author. Tel.: +61 2 9385 2471; fax: +61 2 9385 8016. E-mail address: d.tracey@unsw.edu.au (D.J. Tracey). www.elsevier.com/locate/pain Pain 132 (2007) S22–S25