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.
aProgram in Neuroscience, Florida State University, Tallahassee, FL 32306, USA
bDepartment of Psychological and Brain Sciences and the Gill Center, Indiana University, Bloomington IN 47405, USA
*Corresponding author. Address: Program in Neuroscience/Psychology, Florida State University, 1107W. Call St., Tallahassee, FL 32306–4301, USA. Tel.: +1 850 644 5741; fax: +1 850 644 9874.
1Present address: Merck Research Laboratories, Boston, MA 02115, USA.
2Present address: Vanderbilt University Medical Center, Nashville, TN 37232, USA.
3Present address: Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Submitted June 19, 2010; revised August 17, 2010; accepted August 20, 2010.