Why You Should Consider Central Mechanisms When Treating Endometriosis

Recently, there has been an explosion of research into endometriosis associated pain and the influence of central mechanisms in the pain experience.  Endometriosis-associated pain syndrome (EAP) is defined as “chronic or recurrent pelvic pain in patients with laparoscopically confirmed endometriosis”, and the term is used when the symptoms persist despite adequate endometriosis treatment.1
“It is often associated with negative cognitive, behavioural, sexual or emotional consequences, as well as with symptoms suggestive of lower urinary tract, sexual, bowel or gynaecological dysfunction.”1 Engler et al 2021 also extend this definition to comment that endometriosis may be an incidental finding, is not always painful, and the degree of disease seen laparoscopically does not correlate well with symptom severity. This is routinely seen in clinical practice, where many patients continue to experience debilitating pelvic pain, bladder, bowel or sexual dysfunction despite optimal gynaecological treatment and laparoscopic excision of the endometrial lesions. 
 

Why Does Endometriosis Associated Pain Persist?

 
The presence of endometrial lesions may contribute to local inflammatory and nociceptive input. It is widely accepted that persistent pain will occur due to a multitude of other factors, beyond the endometrial lesions 2-7 including uterine, urologic, gastrointestinal, musculoskeletal, nervous system and psychological factors7.  This can lead to further nervous system sensitisation, including a combination of peripheral, central and cross-organ sensitisation8.  
 
Whilst further study and validation is needed, Yong and co-authors (2020) proposed that EAP could be classified into four different phenotypes7
Type I: pain primarily due to endometriosis lesions and associated inflammation/neurogenesis; 
Type II: pain primarily due to comorbid pelvic condition(s); 
Type III: pain due to central factors; 
Type IV: mix of types I–III. 
 

What do the terms ‘Central Pain Mechanisms’ and ‘Central Sensitisation’ mean?

 
Belgian physiotherapist and pain researcher Dr Jo Nijs is a leader in the study of central pain mechanisms and their implication for clinical practice.  He states these mechanisms include changes to sensory processing in the brain, reduced functioning of the descending inhibitory pathways (the brake) and increased activity of facilitatory nociceptive pathways (the accelerator)9. The accelerator is further enhanced by emotions and thoughts.  The combination of increased acceleration and decreased brakes within the central nervous system leads to the picture of altered (often increased) sensitivity to multiple stimuli such as pressure, stress, light, cold, heat, chemicals, sound and electricity.  Central sensitisation is one component of central pain mechanisms, and is the most commonly used term in the literature.  Nijs describes central sensitisation as “an amplification of neural signalling within the central nervous system that elicits pain hypersensitivity9.”
 
Central pain mechanisms can be recognised clinically by a number of typical features, which include:
Severe pain disproportionate to that expected, based on observed tissue involvement
Spreading pain that doesn’t fit a peripheral / segmental nerve distribution
Hyperalgesia and/or allodynia
Diffuse pain
Psychosocial factors including fear/catastrophising
Pain modulated by emotional factors
Unpredictable aggravating and relieving factors
Sensitivity to temperature, bright lights and odours
 

Why Should We Assess for Central Pain Mechanisms?

 
If central pain mechanisms are present, it predicts poor outcome following classical local treatments such as electrotherapy, motor control exercises and surgery.  Treatment of patients in whom central sensitisation is present should address the lifestyle factors that sustain the process of central sensitisation, including illness beliefs, stress, sleep, physical activity and diet.10
 

How Do We Assess For Central Pain Mechanisms?

 
When assessing EAP, it is important to start with a thorough history to carefully consider the various contributors of both central and peripheral pain mechanisms.  Each patient presents with substantial variability of these factors.  This variability demands a biopsychosocial approach utilising a multi-disciplinary team, to address the specific phenotypes of peripheral and central factors within each patient2
 
One tool that may be used to assess central pain mechanisms is the Central Sensitisation Inventory (CSI).  It has high reliability and validity and has recently been tested in an endometriosis population11.   A score of greater than 40 in Part A indicates that central pain mechanisms are likely present. Part B lists common conditions that are associated with central sensitisation eg. irritable bowel syndrome or fibromyalgia. If a patient scores > 40 OR has one or more of the comorbid conditions in Part B, the likelihood of central pain mechanisms influencing their pain journey is greater.
 

The Entire Health Care Team Should Consider Central Mechanisms

It is important that everyone involved in supporting those who experience endometriosis think beyond the pelvis and considers central pain mechanisms. The CSI is a simple and practical tool that can be used to assist in phenotyping patients with EAP and also help to counsel patients on the presence of central factors that may be influencing their pain6, so that appropriate referrals can be made (eg to physiotherapy, psychology, dietician, exercise physiologist) and the appropriate lifestyle factors can be addressed as part of their treatment plan.   This is more likely to be effective at improving pain, function and quality of life for these patients2.
 
References 
1. Engeler D, Baranowski AP, Berghmans B, Borovicka J, Cottrell A, DinisOliveira P, et al. 2021 EAU Guidelines on Chronic Pelvic Pain: European Association of Urology. Available online at: https://uroweb.org/ guideline/chronic-pelvic-pain/ (accessed August 14, 2021)
2. Allaire C, Aksoy T, Bedaiwy M, Britnell S, Noga HL, Yager H et al. 2017 An interdisciplinary approach to endometriosis-associated persistent pelvic pain. J Endometr Pelvic Pain Disord; 9(2): 77-86
3. McPeak AE, Allaire C, Williams C, Albert A, Lisonkova S and Yong P. 2018 Pain Catastrophizing and Pain Health-Related Quality-of-Life in Endometriosis.  Clin J Pain. 34(4): 349-356
4. Maddern J, Grundy L, Castro J and Brierley SM.  Pain in Endometriosis. 2020 Front Cell Neurosci; 14.  DOI 10.3389/fncel.2020.590823
5. Zheng P, Zhang W, Leng J and Lang J. 2019 Research on central sensitization of endometriosis-associated pain: a systematic review of the literature.  Journal of Pain Research. 12: 1447-1456
6. Orr NL, Wahl KJ, Noga H, Allaire C, Williams C, Bedaiwy MA et al. 2020 Phenotyping Sexual Pain in Endometriosis Using the Central Sensitisation Inventory.  J Sex Med. 17:761-770
7. Yong PJ, Williams C, Behaiwy MA and Allaire C.  2020 A Proposed Platform for Phenotyping Endometriosis-Associated Pain: Unifying Peripheral and Central Pain Mechanisms.  Current Obstetrics and Gynecology Reports. 9:89-97
8. McNamara HC, Frawley HC, Donoghue JF, Readman E, Healey M, Ellett L et al.  2021 Peripheral, Central, and Cross Sensitization in Endometriosis-Associated Pain and Comorbid Pain Syndromes: Frontiers in Reproductive Health. 3: DOI: 10.3389/frph.2021.72642
9. Nijs J, Goubert D and Ickmans K.  2016 Recognition and Treatment of Central Sensitization in Chronic Pain Patients: Not Limited to Specialized Care.  JOSPT. 46(12); 1024-1028
10. Nijs, J., Polli, A., Willaert, W., Malfliet, A., Huysmans, E., & Coppieters, I. 2019. Central sensitisation: another label or useful diagnosis? Drug And Therapeutics Bulletin, 57(4), 60-63. doi: 10.1136/dtb.2018.000035
11. Orr NL, Wahl KJ, Lisonek M, Joannou A, Noga H, Albert A et al. 2021 Central Sensitisation inventory in Endometriosis. PAIN: May 24, doi: 10.1097/j.pain.0000000000002351