Altered GABA_A receptor function in women with endometriosis: a possible pain-related mechanism

The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABA_A ) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABA_A receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABA_A receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABA_A receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABA_A receptor, in the participating women.

15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom-free, control women, aged 18-40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection.

Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABA_A receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels.

Women with painful endometriosis show altered GABA_A receptor function, depicted as a muted response to an exogenous GABA_A receptor agonist.