title: Ectopic uterine tissue as a chronic pain generator.
abstract: While chronic pain is a main symptom in endometriosis, the underlying mechanisms and effective therapy remain elusive. We developed an animal model enabling the exploration of ectopic endometrium as a source of endometriosis pain. Rats were surgically implanted with autologous uterus in the gastrocnemius muscle. Within two weeks, visual inspection revealed the presence of a reddish-brown fluid-filled cystic structure at the implant site. Histology demonstrated cystic glandular structures with stromal invasion of the muscle. Immunohistochemical studies of these lesions revealed the presence of markers for nociceptor nerve fibers and neuronal sprouting. Fourteen days after surgery rats exhibited persistent mechanical hyperalgesia at the site of the ectopic endometrial lesion. Intralesional, but not contralateral, injection of progesterone was dose-dependently antihyperalgesic. Systemic administration of leuprolide also produced antihyperalgesia. In vivo electrophysiological recordings from sensory neurons innervating the lesion revealed a significant increase in their response to sustained mechanical stimulation. These results are consistent with clinical and pathological findings observed in patients with endometriosis, compatible with the ectopic endometrium as a source of pain. This model of endometriosis allows mechanistic exploration at the lesion site facilitating our understanding of endometriosis pain.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Alvarez
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Hendrich
authors.forename: J C
authors.initials: JC
authors.lastname: Irwin
authors.forename: P G
authors.initials: PG
authors.lastname: Green
authors.forename: L C
authors.initials: LC
authors.lastname: Giudice
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000077770:Amifampridine; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001703:Biophysics; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002478:Cells, Cultured; D059350:Chronic Pain / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004715:Endometriosis / Q000150:complications* / Q000209:etiology; D004717:Endometrium / Q000294:innervation / Q000473:pathology; D030762:Estrous Cycle; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D037102:Lectins; D016729:Leuprolide / Q000627:therapeutic use; D018482:Muscle, Skeletal / Q000637:transplantation; D009412:Nerve Fibers / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011374:Progesterone / Q000633:toxicity; D011372:Progestins / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D019737:Transplants / Q000009:adverse effects; D014599:Uterus / Q000294:innervation* / Q000473:pathology* / Q000637:transplantation
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019922:GAP-43 Protein; D037102:Lectins; D026902:Potassium Channel Blockers; D011372:Progestins; D011374:Progesterone; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D016729:Leuprolide; D015740:Calcitonin Gene-Related Peptide; D000077770:Amifampridine