6Pathophysiology of endometriosis-associated pain: A review of pelvic and central nervous system mechanisms
Introduction
Pelvic pain is the commonest presenting symptom of endometriosis. Chronic pelvic pain (i.e. pain perceived to originate in the pelvis lasting for longer than 6 months [1]) and endometriosis are often comorbid but each can exist without the other. For example, it is described that up to 82% of women with chronic pelvic pain have endometriosis [2], but it is also well known that some women with endometriosis experience no pain at all [3]. Furthermore, the relationship between pain and the extent/location/type of endometriosis found at laparoscopy (as measured using rAFS [4]) is much more complex than might be expected [5], [6].
In this review, we will consider mechanisms in the pelvis (periphery) and the central nervous system (central), which may contribute to the generation and/or maintenance of pain in women with endometriosis. Whilst we focus on evidence from the literature on endometriosis, we also focussed parallel on studies with other conditions associated with chronic pain. Finally, we discuss what this means looking forward to the future, both in terms of treatment regimens and research in endometriosis-associated pain.
Section snippets
What is pain?
Before we specifically consider endometriosis-associated pain, it is important to understand pain more generally. Pain is defined as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’ [7]. Pain is a very complex, subjective experience and is thus difficult to pin down; however, it can be described both in terms of the mechanism(s) by which it arises and by the location/triggers of the pain. For definitions of
Nerve fibres & the autonomic nervous system
As described above, nerves are responsible for conveying nociceptive signals from the periphery to the brain. Therefore, it is logical to try to determine whether, in patients with pain, there is a change to these nerves, which could lead to alterations in the signals the brain is receiving about nociception. Alterations in the structure or function of peripheral nerves have been demonstrated in a variety of conditions associated with chronic pain (e.g. osteoarthritis [24], painful
Brain function
There is a very large body of work that shows that there are changes in brain function associated with chronic pain. The most commonly used techniques to investigate brain function in pain are functional MRI (fMRI) and PET imaging. These both give an indirect measurement of activity, as they measure metabolic activity (which increases in active areas), as opposed to electrical activity. One problem with neuroimaging studies that investigate the response to a noxious stimulus is the
Summary
In this chapter, we have reviewed evidence for mechanisms by which endometriosis-associated pain may arise. The key mechanisms discussed are summarised in Fig. 2, which pulls together different factors that influence the perception of endometriosis-associated pain.
We have presented evidence showing changes in the periphery during endometriosis, which includes changes in the nerve growth in the pelvis such as increased sensory nerve fibre growth and decreased sympathetic nerve fibre growth.
Conflicts of interest
Lydia Coxon has no conflicts of interest. Andrew Horne receives grant funding from Ferring and research support from Roche. Katy Vincent receives grant funding from Bayer Healthcare and has received fees for consultancy and honoraria for conference presentations from Bayer HealthcareBayer HealthCare, Grunenthal GmBH and AbbeVie.
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