Presented at the 2012 AAPM Annual Meeting « Back

Unraveling the Enigma of Chronic Pelvic Pain

John S. McDonald, MD, jsm5525@ucla.edu¹, Jichang Li, MD¹, Andrea J. Rapkin, MD², Victor Chaban, PhD³, Paul E. Micevych, MD², (1) Harbor-UCLA Medical Center, Torrance, California, (2) UCLA, Los Angeles, California, (3) Charles Drew University, Los Angeles, California

Introduction: Studies suggest that 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 and applied clinical research to examine responses at DRG neurons innervating viscus for possible mechanisms involving chronic pelvic pain (CPP). Methods: DRG neurons were retrograde labeled by injecting fluorescences into colonic and uterine wall. Inflammation was induced by injecting mustard oil into uterine lumen in rats. DRGs of L1-S3 were cut at 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 and cultured for calcium imaging stimulated by ATP & its modulation by estradiol and mGluR(2/3) inhibitor LY341495. Results: 1. 7% DRG neurons were colon-specific, 11% uterus-specific, and 3% neurons innervating both uterus & colon. 2. Inflammation increased pERK and SP immunoreactivity in DRG neurons innervating both uterus & colon. 3. Estradiol attenuated ATP-induced intracellular calcium increase in 60% of DRG neurons. Co-application of estradiol & mGluR (2/3) inhibitor LY341495 blocked estradiol attenuation of ATP-induced intracellular calcium increase. Conclusions: 1. DRG neurons innervating uterus and colon were identified. 2. Inflammation increased immunoreactivity of pERK and SP in DRG neurons innervating uterus & colon. 3. The rapid action of estradiol in DRG neurons interacts with mGluRs. 4. Results suggest visceral sensory integration in DRG may underlie comorbidity of CPP in women. References: 1)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)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)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