J Pain. 2015 Oct 05. doi: 10.1016/j.jpain.2015.09.008. [Epub ahead of print]

Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain

As-Sanie S, Kim J, Schmidt-Wilcke T, Sundgren PC, Clauw DJ, Napadow V, Harris RE.

Abstract

In contrast to women with relatively asymptomatic endometriosis, women with endometriosis-associated chronic pelvic pain (CPP) exhibit non-pelvic hyperalgesia and decreased gray matter volume in key neural pain processing regions. While these findings suggest central pain amplification in endometriosis-associated CPP, the underlying changes in brain chemistry and function associated with central pain amplification remain unknown. We performed proton spectroscopy and seed-based resting functional connectivity MRI to determine whether women with endometriosis display differences in insula excitatory neurotransmitter concentrations or intrinsic brain connectivity to other pain-related brain regions. Relative to age-matched pain-free controls, women with endometriosis-associated CPP displayed elevated levels of combined glutamine-glutamate (Glx) within the anterior insula, and greater anterior insula connectivity to the medial prefrontal cortex (mPFC). Increased connectivity between these regions was positively correlated with anterior insula Glx concentrations (r=0.87), as well as clinical anxiety (r=0.61,p=0.02), depression (r=0.60,p=0.03), and pain intensity (r=0.55,p=0.05). There were no significant differences in insula metabolite levels or resting-state connectivity in endometriosis without CPP subjects versus controls. We conclude that enhanced anterior insula glutamatergic neurotransmission and connectivity with the mPFC, key regions of the salience and default mode networks, may play a role in the pathophysiology of CPP independent of the presence of endometriosis.
PERSPECTIVE: Similar to other chronic pain conditions, endometriosis-associated pelvic pain is associated with altered brain chemistry and function in the pain matrix. These findings support central pain amplification as a mechanism of CPP, and clinicians should consider the use of adjunctive therapies that target central pain dysfunction in these women.

PMID: 26456676