Presented at the 2013 AAPM Annual Meeting « Back

Unraveling the Enigma of Chronic Pelvic Pain

John S. McDonald, MD, nikki1@ucla.edu¹, Jichang Li, MD¹, Andrea J. Rapkin, MD², Victor Chaban, PhD MS³, Paul Micevych, PhD² , (1) Harbor-UCLA Medical Center, Torrance, California, (2) David Geffen School of Medicine at UCLA, Los Angeles, California, (3) UCLA and Charles Drew University, Los Angeles, California

Introduction: Studies suggest syndromes such as IBS are often comorbid with chronic pelvic pain in women. The possible explanation is visceral-visceral cross-sensitization. This abstract is the combined results of 5 years of both basic science & applied clinical research to examine responses at DRG neurons innervating viscus for possible mechanisms involving chronic pelvic pain. Methods: DRG neurons were labeled by injecting fluorescences into colonic & uterine wall. Inflammation was induced by injecting mustard oil into uterine lumen in rats. DRGs of L1-S3 were cut 20 µm thick, incubated in antibody for pERK and SP. The number of pERK or SP positive neurons was counted under fluorescent microscopy. DRG neurons were also acutely isolated by enzyme & cultured for calcium imaging stimulated by ATP & its modulation by estradiol & mGluR (2/3) inhibitor LY341495. Results: 1. 7% DRG neurons were colon-specific, 11% uterus-specific, & 3% neurons innervating both uterus & colon. 2. Uterus & colon inflammation increased pERK & SP immunoreactivity in DRG neurons. 3. Estradiol attenuated ATP-induced intracellular calcium increase in 60% of DRG neurons. Co-application of estradiol and mGluR (2/3) inhibitor LY341495 blocked estradiol attenuation of ATP-induced intracellular calcium increase. Conclusions: 1. DRG neurons innerved uterus & colon were identified. 2. Inflammation increased immunoreactivity of pERK & SP in DRG neurons innervating both uterus & colon. 3. Rapid action of estradiol in DRG neurons involves interaction with mGluRs. 4. Results suggest visceral sensory integration in DRGs may underlie comorbidity of chronic pelvic pain in women. References: 1) Latthe P, Mignini L, Gray R, Hills R, Khan K. Factors predisposing women to chronic pelvic pain: systematic review. BMJ. 332:749-55, 2006. 2) Friedrich-Karl Pierau, Gerd Fellmer and David C. M.Taylor . Somato-Visceral Convergence in Cat Dorsal Root Ganglion Neurones Demonstrated by Double-Labelling With Fluorescent Tracers. Brain Research, 321: 63-70, 1984. 3) Guang-Yin Xu and Li-Yen Mae Huang. Peripheral Inflammation Sensitizes P2X Receptor-Mediated Responses in Rat Dorsal Root Ganglion Neurons. The Journal of Neuroscience, 22(1): 93-102, 2002

Funding: None