The Clinical Significance of Endocannabinoids in Endometriosis Pain Management
Jerome Bouaziz, Alexandra Bar On, Daniel S. Seidman, and David Soriano
Cannabis and Cannabinoid Research, 2017, 2, 1, 72-80
DOI : 10.1089/can.2016.0035
Introduction : Patients with endometriosis often suffer from diffuse and poorly localized severe pain. The current pain management strategies include medical and hormonal therapy, as well as surgery. Medical management of pain is often insufficient and is associated with high rate of recurrence. Better pain management is therefore of urgent need.
Methods : Among the various candidates, the endocannabinoid system (ECS) has recently emerged as a relevant pharmacological target for themanagement of endometriosis-related pain. Acomputerized literature searchwas performed to identify relevant studies combining the keywords ‘‘endometriosis,’’ ‘‘endocannabinoid,’’ ‘‘cannabinoid receptor,’’ ‘‘THC,’’ and ‘‘pain mechanisms.’’
Conclusions : This review describes the multiple and complex pain mechanisms associated with endometriosis. Current data and theories concerning the link between the ECS and pain management for endometriosis patients are presented. Finally, we will discuss which aspects of endometriosis-associated pain can be targeted by modulation of the ECS.
Keywords : cannabis; endocannabinoid; endometriosis; pelvic pain
Endometriosis is defined as the presence of endometrial glands or stroma in sites other than the uterine cavity, such as the ovaries, pelvic peritoneum, and the rectovaginal septum.1 This condition affects 5–15% of the women of reproductive age.2 Pain is one of the predominant clinical features of endometriosis. The patients often suffer from diffuse and poorly localized severe pain. It has an impact on the quality of life in many ways. Pain in endometriosis is often associated with psychological distress and fatigue, both of which may amplify pain.3 In more than 95% of cases, patients who suffer fromdeep infiltrated endometriosis (DIE) are prone to very severe pain. It can also include symptoms such as dysmenorrhea, dyspareunia, nonmenstrual pelvic pain, and, less commonly, dyschezia and dysuria.4
The management of hyperalgesia in endometriosis patients is a medical challenge.1,3,5,6 The current pain management strategies for endometriosis focuses mainly on medical treatments such as hormonal therapy, painkillers or nonsteroidal anti-inflammatory drugs (NSAIDs), and/ or surgical resection. Medical management, however, is insufficient as it is associated with high rate of recurrence7 and imparts only partial relief of symptoms and/or chronic pelvic pain (CPP).3,5,7 Medical and surgical
management also depend on whether the woman presently wants to conceive or not and if she may require an in vitro fertilization (IVF) treatment.
The pathogenesis of endometriosis remains unclear, although it is known that several pathways are involved. The endocannabinoid system (ECS) has emerged recently as an important factor in endometriosis development, maintenance, and pain mechanisms.8–13 These new revelations suggest that the ECS may potentially serve as a pharmacological target for endometriosis treatments, including pain management, and have a role in immune intervention and antiproliferative and antifibrotic effects.
In this review of the literature, we will first discuss the multiple and complex pain mechanisms involved
in endometriosis and then analyze the existing data and theories concerning the link between pain management and ECS in endometriosis patients. Finally, we will review which aspects of endometriosis-associated pain can be targeted by modulation of the ECS.