A PAIN THAT GOES BEYOND ENDOMETRIOSIS
Some women with chronic pelvic pain symptoms consistent with endometriosis have been shown to exhibit signs of pain sensitization1-3
Repeated painful stimulation causes the nerves of the CNS to get more and more sensitive, until4:
- They respond to previously benign stimuli
- Their responses to painful stimuli are exaggerated, prolonged, and spread widely
- A person feels “phantom pain” in the absence of any stimulation at all
This CNS remodeling is known as central sensitization, and for some women with endometriosis, it could mean a level of pain response that feels far beyond “normal.”2-4
Pain due to endometriosis is caused by an increase in inflammatory markers and an amplification in nerve density at the lesion. Endometriosis and its lesions can develop on pelvic organs like the bladder, intestines, and ovaries and can also be found in distant areas like the diaphragm.5,6
Because it engages so many of the body’s systems, and because it is fueled by neural, inflammatory, and hormonal factors (including estradiol), endometriosis pain may cause sensitization.1-3,7
In a cross-sectional, prospective study of women aged 18 to 50 (n=49) with pain suggestive of endometriosis and endometriosis diagnosis by histologic evaluation (n=18), pain without endometriosis diagnosis by histologic evaluation (n=11), and healthy, pain-free volunteers without a history of endometriosis (n=20) conducted at the National Institutes of Health, subjects underwent a psychiatric neuro-musculoskeletal assessment of clinical signs of sensitization it was found that:
82.5% of women with chronic pelvic pain were shown to have clinical signs of pain sensitization vs 15% in the control group1
- Sensitization was defined as the presence of pain due to a non-noxious stimulus (allodynia) or an increased pain response to a noxious stimulus (hyperalgesia)1
New, highly sensitive nerves in endometrial lesions can contribute to sensitization7
Research suggests that a major contributing factor to endometriosis pain is the way in which the newly formed nerves in endometriosis lesions affect the activity of neurons in the spinal cord and brain.
These new nerves7:
- May be more easily activated by stimulation
- May show greater spontaneous activity
- May continue to transmit pain signals even after inflammation has subsided
- May cause referred pain to other areas in the pelvic region
Estradiol and the vicious cycle of pain sensitization7
Evidence shows that estradiol influences the sensitivity of peripheral as well as central nerves. Chronically elevated levels of inflammatory signals have also been shown to contribute to sensitization. Thus, new, highly sensitive nerves, overactive inflammatory signals, and estradiol all contribute to the ongoing cycle of pain sensitization.
- This sensitization can ultimately lead to exaggerated response to pain elsewhere in the body and could account for co-morbidity of pelvic pain with other pain syndromes such as temporomandibular joint (TMJ) disorder or fibromyalgia
Chronic, sensitized pain may be difficult to treat, requiring a multi-therapeutic approach.7
1. Stratton P, Khachikyan I, Sinaii N, Ortiz R, Shah J. Association of chronic pelvic pain and endometriosis with signs of sensitization and myofascial pain. Obstet Gynecol. 2015;125(3):719-728. 2. Bajaj P, Bajaj P, Madsen H, Arendt-Nielsen L. Endometriosis is associated with central sensitization: a psychophysical controlled study. J Pain. 2003;4(7):372-380. 3. Aredo JV, Heyrana KJ, Karp BI, Shah JP, Stratton P. Relating chronic pelvic pain and endometriosis to signs of sensitization and myofascial pain and dysfunction. Semin Reprod Med. 2017;35(1):88-97. 4. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 suppl):S2-S15. 5. Sturpe DA, Pincus KJ. Endometriosis. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed. New York, NY: McGraw-Hill; 2014. 6. Association of Professors of Gynecology and Obstetrics. Diagnosis & Management of Endometriosis: Pathophysiology to Practice. Educational Series on Women’s Health Issues. https://pdfs.semanticscholar.org/2f57/078beb656b74691969f0a494021dca8e094f.pdf. Accessed June 10, 2019. 7. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17(3):327-346.