title: Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents.
abstract: Endometriosis is a painful condition characterized by growth of endometrial cysts outside the uterus. Here, we tested the hypothesis that peripheral innervation and prostaglandin levels contribute to endometriosis-associated pain. Female Sprague-Dawley rats (n = 16) were surgically instrumented by transplanting uterine tissue onto mesenteric arteries within the peritoneal cavity to create a model of endometriosis which forms extra-uterine endometrial cysts and vaginal hyperalgesia. Our results describe a significant positive correlation between endometriosis-induced vaginal hyperalgesia and cyst innervation density (sensory, r = 0.70, p = 0.003; sympathetic, r = 0.55, p = 0.03), vaginal canal sympathetic innervation density (r = 0.80, p = 0.003), and peritoneal fluid levels of the prostaglandins PGE2 (r = 0.65, p = 0.01) and PGF2α (r = 0.63, p = 0.02). These results support the involvement of cyst innervation and prostaglandins in endometriosis-associated pain. We also describe how sympathetic innervation density of the vaginal canal is an important predictor of vaginal hyperalgesia.
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, 94305, USA; Program in Neuroscience, Florida State University, Tallahassee, FL, 32306, USA. Electronic address: smcallis@stanford.edu.
authors.forename: Stacy L
authors.initials: SL
authors.lastname: McAllister
authors.affiliation: Program in Neuroscience, Florida State University, Tallahassee, FL, 32306, USA.
authors.forename: Barbra K
authors.initials: BK
authors.lastname: Giourgas
authors.affiliation: Program in Neuroscience, Florida State University, Tallahassee, FL, 32306, USA.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Faircloth
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IA, 47405, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Leishman
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IA, 47405, USA.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Bradshaw
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gross
mesh_terms: D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003560:Cysts / Q000150:complications / Q000473:pathology*; D004715:Endometriosis / Q000150:complications* / Q000473:pathology*; D005260:Female; D006930:Hyperalgesia / Q000150:complications* / Q000473:pathology*; D011453:Prostaglandins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000294:innervation / Q000473:pathology; D014621:Vagina / Q000294:innervation* / Q000473:pathology*
chemical_list: D011453:Prostaglandins; D015740:Calcitonin Gene-Related Peptide
keywords: Cyst; Endometriosis; Innervation; Pelvic pain; Prostaglandin; Vaginal hyperalgesia