Endocannabinoid involvement in endometriosis

• Type of Material: Article
• Authors: Natalia Dmitrieva, Florida State University; Hiroshi Nagabukuro, Florida State University; David Resuehr, Florida State University; Guohua Zhang, Florida State University; Stacy McAllister, Emory University; Kristina A. McGinty, Florida State University; Ken Mackie, Indiana University; Karen J. Berkley, Florida State University
• Language: English
• Date: 2010-12
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved
• Final Published Version (URL): http://dx.doi.org/10.1016/j.pain.2010.08.037
• Title of Journal or Parent Work: PAIN
• ISSN: 0304-3959
• Volume: 151
• Issue: 3
• Start Page: 703
• End Page: 710
• Grant/Funding Information: This work was supported by National Institutes of Health Grants NS011892 (to K. J. B.) and DA011322 and DA021696 (to K. Mackie).
• Keywords: neural sprouting; visceral pain; transplant; neurovascular; sensory-sympathetic coupling; neuroplasticity
• Research Categories: Biology, Neuroscience; Psychology, Psychobiology; Health Sciences, Medicine and Surgery

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. Here, 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.