Endometriosis and Central Sensitization: Pain in Endometriosis

What's the Link Between Endometriosis and Central Sensitization?

Endometriosis affects roughly about 10% of reproductive-age women, and is characterized by endometrial-like lesions that grow outside of the endometrium (the lining of the uterine wall). Women with endometriosis have symptoms such as: chronic pelvic pain, dysmenorrhea, abdominal pain, infertility, constipation, interstitial cystitis/painful bladder syndrome, and more.

Often endometriosis is treated through hormonal management and/or surgically. However, 18-27% of patients with endometriosis treated via hormonal medications reported no relief from symptoms. About 20% of patients with endometriosis treated through surgical excision or ablation continued to experience chronic pelvic pain and other endometriosis symptoms. Moreover, 70 to 80% of women with chronic pelvic pain with confirmed endometriosis lesions do not have lesions in the areas where they experience symptoms.

How could that be?

We are about to dig in to the science of how chronic pain develops, specifically in endometriosis. More clarification to these terms will be provided below, so hang in there!

Chronic pelvic pain can lead to peripheral and central sensitization via viscerosomatic convergence, which in turn can lead to pain in areas away from the source of the lesion. Central sensitization can also perpetuate pain and decrease the threshold of pain. Endometriosis targeted treatments may not address the pain due to central sensitization and myofascial dysfunction, which can persist even after lesions are removed or managed.

How does central sensitization start?

It starts with an injury or noxious stimulus (a painful insult). As a result, neurons start to fire to signal danger, and inflammatory cells are sent to the site to heal and recover. However, when the noxious stimulus keeps firing, it can lead to peripheral sensitization. Over time, peripheral sensitization leads to central sensitization (read below for more information). 

Peripheral Sensitization

Repeated or prolonged activation of nociceptors (our pain receptors) results in a lower pain threshold known as peripheral sensitization. The lesions can actually innervate (or connect with) nearby blood vessels helping the lesions expand and grow. Due to the lesions, different types of fibers such as C-fibers, sympathetic fibers, tumor necrosis factor-alpha, nerve growth factors, mast cells, etc. are all involved in increasing inflammation, thus causing more pain. 

With peripheral sensitization, neuropeptides are secreted and released into the peripheral tissue after being activated repeatedly. This leads to vasodilation (increasing blood flow), and more immune cells are recruited to these sites. The repetitive firing of nociceptors transmit their signals to the dorsal horn of the spinal cord, and then travel to the brain. Repetitive and prolonged exposure of pain will eventually lead to changes in the central nervous system, initiating the process of central sensitization.

Central Sensitization

Central sensitization is the excessive firing of the nociceptors in the central nervous system and eventually starts to, “amplify and perpetuate the perception of pain long after the initiating pathology resolves.” (Aredo, et al.) Eventually, patients start to experience allodynia (pain from a non-painful stimulus) and/or hyperalgesia (increased pain to a painful stimulus). Three processes may be responsible when it comes to chronic pelvic pain: 

1. Viscerosomatic convergence: visceral (organ) input to the brain almost always includes nearby muscle and skin input via viscerosomatic convergence. This can lead to referred pain patterns and explains why women experience pain in muscles innervated by the same and neighboring spinal segments as the organ (i.e. source is bladder dysfunction, but we may feel more abdominal muscle pain or low back pain instead)
2. Viscerosomatic reflex: both visceral and somatic nociceptors connect with interneurons in the spinal cord that can activate alpha and gamma motor neurons that innervate skeletal muscle. Persistent visceral input can increase muscle tone and instigate spasms in the area of the referred patterns. 
3. Chronic, repeated local pain stimuli may affect the hypothalamic-pituitary-adrenal (HPA) axis leading to decreased cortisol levels and thus exacerbate pain. This can lead to other changes in the brain, such as increased volume in the periaqueductal gray (PAG), which is imperative in pain modulation processes.

Over time, dysfunction in the muscle and surrounding connective tissue via the viscerosomatic processes can lead to myofascial pain and trigger points. Studies have shown that myofascial trigger points are correlated with endometriosis, interstitial cystitis/painful bladder syndrome, vulvodynia, IBS, coccydynia, and urethral syndrome1. Trigger points are small nodules on tight bands of muscles that are thought to be in a sustained state of contracture. Women with confirmed endometriosis often have trigger points in the abdomen and pelvic floor. It is no wonder then, that most women with endometriosis also have pain with sex, constipation, and painful urination (however conditions of these organs can occur concurrently as well).

How do you know if you have central sensitization?

How do you know if you have central sensitization? There is a great outcome measure called the Central Sensitization Inventory or CSI. It has been validated in those with chronic pain conditions to differentiate between centrally sensitized and non-sensitized patients. One study found that specifically for women with endometriosis, a cutoff of 40 on the CSI indicated central sensitization. This study also found that a cutoff of 40 for those with endometriosis was also associated with a younger age onset of symptoms and severity of pain2. 

Physical Therapy and Multidisciplinary Care Program

Once the trigger points are developed, they can be a source of pain on their own, even after the initial insult (endometrial lesions) have been removed or resolved. Physical therapy manual techniques, stretches, joint mobilizations, and exercises/foam rolling can help release trigger points and myofascial pain. In addition, physical therapists can help downregulate the nervous system, train on breathing exercises, and educate on bladder/bowel health. It is important to have a multidisciplinary approach when it comes to central sensitization and may involve other professionals such as counseling/psychotherapy, pain education, and pain/medical management in addition to physical therapy. This is why many endometriosis specialists will sometimes require physical therapy and other complementary alternative therapies before and after endometriosis surgeries to maximize the potential of healing and reducing symptoms. 

Have questions or concerns about endometriosis and central sensitization? Please give our office a call or schedule an appointment through our website.  

References:

Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril 2004;82:878-884. 

Aredo JV, Heyrana KJ, Karp BI, et al. Relating Chronic Pelvic Pain and Endometriosis to Signs of Sensitization and Myofascial Pain and Dysfunction. Semin Reprod Med 2017;35(2):88-97. doi:10.1055/s-0036-1597123

Hsu AL, Sinai N, Segars J, Nieman LK, Stratton P. Relating pelvic pain location to surgical findings of endometriosis. Obstet Gynecol 2011; 118(2Pt 1):223-230. 

Orr NL, Wahl KJ, Lisonek M, et al. Central sensitization inventory in endometrial-like tissue and pelvic pain. Pain 2021;163:e234-e245.

Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients Hum Reprod 2007; 22(1):266-271. 

Yong PJ, Alsowayan N, Noga H, Williams C, Allaire C, Lisonkova S, Bedaiwy MA. CHC for pelvic pain in women with endometriosis: ineffectiveness or discontinuation due to side-effects. Hum Reprod Open 2020;2020:hoz040.

Zheng P, Zhang W, Leng J, Lang J. Research on central sensitization of endometriosis-associated pain: a systematic review of the literature. J Pain Research 2019;12:1447-1456.