title: Endocannabinoid involvement in endometriosis.
abstract: Endometriosis is a disease common in women that is defined by abnormal extrauteral growths of uterine endometrial tissue and associated with severe pain. Partly because how the abnormal growths become associated with pain is poorly understood, the pain is difficult to alleviate without resorting to hormones or surgery, which often produce intolerable side effects or fail to help. Recent studies in a rat model and women showed that sensory and sympathetic nerve fibers sprout branches to innervate the abnormal growths. This situation, together with knowledge that the endocannabinoid system is involved in uterine function and dysfunction and that exogenous cannabinoids were once used to alleviate endometriosis-associated pain, suggests that the endocannabinoid system is involved in both endometriosis and its associated pain. Herein, using a rat model, we found that CB1 cannabinoid receptors are expressed on both the somata and fibers of both the sensory and sympathetic neurons that innervate endometriosis's abnormal growths. We further found that CB1 receptor agonists decrease, whereas CB1 receptor antagonists increase, endometriosis-associated hyperalgesia. Together these findings suggest that the endocannabinoid system contributes to mechanisms underlying both the peripheral innervation of the abnormal growths and the pain associated with endometriosis, thereby providing a novel approach for the development of badly-needed new treatments.
authors.affiliation: Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA Department of Psychological and Brain Sciences and the Gill Center, Indiana University, Bloomington IN 47405, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Dmitrieva
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagabukuro
authors.forename: David
authors.initials: D
authors.lastname: Resuehr
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhang
authors.forename: Stacy L
authors.initials: SL
authors.lastname: McAllister
authors.forename: Kristina A
authors.initials: KA
authors.lastname: McGinty
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Berkley
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D004576:Electromyography; D004715:Endometriosis / Q000150:complications / Q000378:metabolism*; D004717:Endometrium / Q000294:innervation* / Q000378:metabolism; D005260:Female; D006930:Hyperalgesia / Q000150:complications / Q000378:metabolism*; D007150:Immunohistochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism*; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D043884:Receptor, Cannabinoid, CB1; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D015740:Calcitonin Gene-Related Peptide