Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study

Abstract

Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15%-20% of women in the United States. Endometriosis is often associated with CPP, however, other factors, such as preexisting or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing. Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, and 23 healthy controls. All patients with endometriosis and/or CPP were surgically confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception, including the left thalamus, left cingulate gyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis who had no CPP. We conclude that CPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis.

Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1. Overview of study population

N = number; ⊕Endo⊕Pain = endometriosis with chronic pelvic pain; ⊕Endo∅Pain = endometriosis without chronic pelvic pain, ∅Endo⊕Pain = chronic pelvic pain without endometriosis. * Each subgroup of endometriosis/chronic pelvic pain group (groups 1-3) was compared to an age-matched subset of healthy controls.

Figure 2. Gracely Box scale measures of pelvic pain intensity (left) and unpleasantness (right)

The Gracely Box Scale (GBS) is a numerical scale that is used to evaluate pain intensity and unpleasantness (GBS pelvic pain intensity and unpleasantness). This scale is comprised of 21 boxes, sequentially numbered beginning with 0 and ending with 20. It is aligned vertically, with 0 representing the least amount of pain. Descriptive words are arranged next to the numbers corresponding with increasing levels of pain intensity and unpleasantness.

Figure 3. Results from VBM analysis

Statistical parametric maps (SPM) demonstrating differences between groups (t-test with age as a covariate of no interest). Figure A and B: decreased gray matter volumes (in red) in the cingulate gyrus, the right putamen, and the left thalamus in the ⊕Endo⊕Pain group as compared to healthy controls. Figure C and D: increased gray matter volume (in yellow) in the right PAG in the ⊕Endo∅Pain group as compared to healthy controls. Figures Eand F: decreased gray matter volume (in red) in the left thalamus in the ∅Endo⊕Pain group as compared to healthy controls. P

Figure 4. Scatter plot: pain thalamic gray matter vs. pain unpleasantness in the ⊕Endo⊕Pain group

Correlation analysis between left thalamic gray matter (GM), and pelvic pain unpleasantness ratings in the ⊕Endo⊕Pain group.GM values were extracted from the cluster in the left thalamus identified in the group comparison between the ⊕Endo⊕Pain group and healthy controls. GBS = Gracely Box Scale, pain unpleasantness in last month.

Figure 5. Dysmenorrhea, Endometriosis, and CPP – a conceptual approach to pain chronification

Possible mechanisms of pain chronification in patients with dysmenorrhea and/or endometriosis.Box A:Initially,anociceptive sourceserves as a “pain generator”, inducing cyclic pain (dysmenorrhea) and associated changes in regional brain morphology and metabolism.A nociceptive input can be created via sensitized nerve fibers surrounding endometriosis lesions within the pelvis, nerve fiber proliferation in the uterus and/or endometrium (which can also occur in the absence of endometriosis), prostaglandin mediated uterine contractions,or other peripheral abnormalities.*Central factors, such as direct sex hormone-CNS interactions, may also act as pain generators by sensitizing the brain to nociceptive neural input. Box B:Dysmenorrhea and initial changes in regional brain morphology and metabolismmay remain stable or may show further changes, eitheradaptive or maladaptive.Box C: Those women who progress to chronic pelvic pain (CPP) show maladaptive changes in the pain system. Less commonly, this may occur without a preceding phase of dysmenorrhea (arrow 1c). Box D: Those women who experience resolution of their dysmenorrhea (2a) or CPP (3), and those who do not experience pelvic pain despite having a peripheral pain generator (1b) showa “normalization”of or no change in GM volume in the thalamus, insular cortex and cingulate cortex, but have an associated increase in GM volume in the periaqueductal gray (PAG). ** Hypothetically, an increase in GM volume in the PAGis associated with a gain of function of the antinociceptive system.