Do you have a female friend or family member who coughs up blood at the time of her period? This rather bizarre occurrence is a very rare, yet documented clinical feature of endometriosis [1]. Endometriosis occurs when tissue similar to the lining of the uterus (the endometrium) lodges outside the uterus and induces an estrogen-dependent inflammatory reaction. The most common places to find endometrial-like tissue are the on the walls of the pelvic cavity, the ovaries, bladder and bowel, and on the thin wall dividing the rectum from the vagina. In very rare instances, endometrial-like tissue has been found in the lungs, which explains the bloody cough at the time of menstruation. The condition affects in the realm of 176 million women worldwide.
Aside from pain, particularly at ovulation and menstruation, during or after sexual intercourse, during urination and bowel movements, and subfertility, other features of endometriosis include fatigue, bloating, nausea, and heavy bleeding during periods. Endometriosis can start with a girl’s first period, the endometrial cells making their way into the pelvic cavity via backward menstruation, or after surgery. Family genetics and/or exposure to environmental toxins may also play a role. Most commonly, endometriosis is reported between the start of periods and menopause.
There is often a significant delay in the diagnosis of endometriosis, primarily because pain during menstruation is thought to be ‘normal’ and perhaps because there is often a complex pattern of pain features in endometriosis. For example, an individual might report a constant non-cyclical pelvic-region pain, that only changes mildly in severity, as well as severe dysmenorrhoea (heavy bleeding and pain during periods), and specific function-related pain such as pain during bowel movements.
This raises the possibility that different mechanisms underpin different features of the condition and a recent review led by researchers at the Nuffield Department of Obstetrics and Gynaecology, University of Oxford has compiled valuable information about our current understanding and theories on possible peripheral and central pain mechanisms in endometriosis [2]. Here is a brief summary over two blog posts (this first one highlights peripheral mechanisms), and as our Molly Meldrum used to say each week – do yourselves a favour and get the full paper!
Potential contributions from peripheral mechanisms are numerous. Firstly, changes in the peritoneal (or pelvic cavity) fluid in women with endometriosis includes increased levels of pro-nociceptive substances such as cytokines and growth factors which are released by immune cells as part of the local inflammation generated around the endometrial-like cells. These proteins can directly and indirectly (via feedback loops) sensitise peripheral nerves.
Secondly, a growing body of literature reports that new nerve fibres grow into endometriotic clusters, but as yet, there is no clear correlation between nerve fibre density and the pain severity. Thirdly, there is a local increase in sympathetic nerve fibres distant to the endometriotic clusters, and a loss of sympathetic nerve fibres close to the clusters. It is thought that this qualitative change in nerve fibres might be important in maintaining a pro-inflammatory state around the clusters.
You might think that with all this inflammation at a time of high estrogen, that the obvious treatment would be anti-inflammatories and anything that suppresses estrogen release, and indeed medications that do that currently comprise the front line of medical intervention [3]. For many women, however, they afford limited or intermittent benefit suggesting that other mechanisms also need to be considered….and they will be in the next instalment…stay tuned.
Carolyn Berryman
Carolyn finished her PhD with BiM in 2015 exploring chronic pain, somatic hyper vigilance and cognitive function and is pursuing her research and teaching interests in chronic pain and cognitive function with clinical application.
Carolyn has masters degrees in physiotherapy and medical science (pain management). Before winning an Australian Postgraduate Award to return to study she taught pain sciences to under and post graduate physiotherapy students at UniSA with the Noisters and ran her own clinic for a couple of decades. Way back in 1995 she was co-convenor of the inaugural Moving in on Pain conference in Adelaide. Now she uses that experience to inspire and mentor the next generation of interest in pain sciences at Uni SA.
References
- Guidice, L. and L. Kao, Endometriosis. Lancet 2004. 364: p. 1789-1799.
- Morotti, M., K. Vincent, and C. Becker, Mechanisms of pain in endometriosis. European Journal of obstetrics and gynecology and reproductive biology, 2017. 209: p. 8 – 13.
- Becker, C., et al., Reevaluating response and failure of medical treatment of endometriosis: a systematic review. Fertility and Sterility, 2017. 108: p. 125 – 135.
- As-Sanie, S., R. Harris, and V. Napadow, Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. Pain, 2012. 153: p. 1006-1014.
- Vincent, K., et al., Dysmenorrhoea is associated with central changes in otherwise healthy women. Pain, 2011. 152: p. 1966-1975.
- Tu, C., D. Niddam, and H. Chao, Brain Morphological changes assciated with cyclic menstrual pain. Pain, 2010. 150: p. 462-468.