Chronic Pelvic Pain Not Sufficiently Explained by Presence of Endometriosis

Women with chronic pelvic pain had greater connectivity in "pain" regions of the brain, regardless of presence of endometriosis.

Chronic pelvic pain (CPP) is experienced by women with and without endometriosis and has been found to be associated with elevated levels of combined glutamine-glutamate within the anterior insula as well as greater anterior insula connectivity to the medial prefrontal cortex, according to research published in The Journal of Pain.

The researchers found that women with endometriosis and CPP had increased concentrations of excitatory neurotransmitters in the anterior insula and greater intrinsic connectivity of the same anterior insula region to the medial prefrontal cortex. Both of these regions are known to be important in processing pain. Increased connectivity between these regions was also correlated with higher concentrations of combined glutamine and glutamate (GIx), as well as with higher symptom severity in pain intensity, anxiety, and depression.

TRENDING ON CPA: Opioid Precaution During Cold and Flu Season: Medication Adjustment May Be Required

Patients without endometriosis who had CPP showed similar elevated excitatory neurotransmitters in the anterior insula, but patients with endometriosis who had no CPP did not show increased insular metabolite levels or resting connectivity compared with the control group. 

It is possible that patients with endometriosis who do not have CPP “experience little if any pelvic pain due to adaptive, anti-nociceptive activity,” the researchers wrote. “Our findings and others suggest that each person’s clinical pain experience is likely determined by a complex interaction between peripheral factors (such as endometriosis), anti-nociceptive capacity (such as activity of the periaqueductal gray), and maladaptive changes in the CNS pain regulatory system.”

The investigators evaluated 17 women with endometriosis who had CPP, 13 women with endometriosis without CPP, 6 women without endometriosis who did have CPP, and 24 healthy women as controls. All participants were between the ages of 18 and 52 and had not undergone prior hysterectomy or bilateral oophorectomy.

The researchers used proton magnetic resonance spectroscopy (1H-MRS) to measure the excitatory neurotransmitter concentrations N-acetylaspartate (NAA) and GIx in the right anterior and posterior insula. They used seed-based resting functional connectivity MRI to determine whether women with endometriosis display differences in intrinsic brain connectivity to other pain-related brain regions.

These findings may explain why some women do not experience relief of CPP when undergoing therapies aimed at eliminating endometriosis and have important implications for evaluating and managing CPP in women. For example, some women may be able to avoid repetitive surgeries to address pelvic pathology because they would benefit more from pharmacologic and cognitive therapies aimed at central pain amplification. Identifying which patients would benefit from which treatments would be a critical step forward in developing personalized approaches for treating CPP.

Editor’s Note: The original version of this article incorrectly identified activation of the insula as being reflective of brain dysfunction. Although endometriosis-associated pelvic pain is associated with alterations in the brain, this can be considered a normal response. The article was corrected on November 2, 2015, to reflect this.


As-Sanie S, Kim J, Schmidt-Wilcke T, et al. Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain. J Pain. 2015; doi:10.1016/j.jpain.2015.09.008.