“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.”
“These findings implicate involvement of the endocannabinoid system in reproductive function and dysfunction. The endocannabinoid system plays a key role in pain mechanisms, and, previously, cannabinoids were long used by women to alleviate dysmenorrhea.”
“Together the findings suggest that the endocannabinoid system is involved in endometriosis and its associated pain via CB1 receptors and innervation of the ectopic growths. Using the rat model, we performed a combination of immunohistochemical and pharmacological studies to test this hypothesis and assess the endocannabinoid system’s potential as a target for new therapies.”
Summary and conclusions
“These studies in a rat model of endometriosis provide evidence that endocannabinoids might regulate the innervation of the disease’s abnormal growths and that exogenous cannabinoid agents can be effective in reducing endometriosis symptoms. The fact that CB1 receptor expression is greater in the cysts than healthy uterus from the same rats suggests that treatments to activate CB1 receptors (either directly by CB1 agonists or indirectly by increasing relevant endocannabinoid levels) could be developed with minimal effects on uterine function. Although the rat model parallels many aspects of endometriosis in women, there are of course significant differences. However, when considered together with the past history of successful use of cannabinoids for alleviation of gynecological pains, and insofar as findings in rats can model mechanisms of endometriosis-related signs and symptoms, the present results suggest that approaches targeted at the endocannbinoid system represent a promising new direction for developing badly-needed new treatments for pain suffered by women with endometriosis.”
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