Endocannabinoid involvement in endometriosis

Dmitrieva et al. ·Pain Impact 4.2

Clear benefit GRADE Very low 64 citations

SamplePräklinisch

Durationunclear

ControlCB1 receptor antagonists

EndpointEndometriosis-associated…

Blindingn.a.

DesignPräklinisch

Key finding

CB1 receptor agonists reduced endometriosis-associated hyperalgesia in a rat model; CB1 antagonists increased it.

Summary

Preclinical study on the endocannabinoid system in endometriosis; evidence of reduced CB1 receptor expression and altered anandamide levels in ectopic endometrium, indications of ECS dysregulation as a pathophysiological factor

PopulationRats with experimental endometriosis (animal model), number not specified in the abstract

InterventionCB1 cannabinoid receptor agonists (substance and dose not stated in the abstract)

ControlCB1 receptor antagonists (as control intervention to validate the mechanism of action)

OutcomeCB1 agonists reduced endometriosis-associated hyperalgesia, CB1 antagonists increased it (no quantitative data in the abstract)

Confidence in the evidence

Very low

The lowest GRADE level, the effect estimate remains uncertain.

Downgraded for

Indirectness

Quality profile

Sample size —

Blinding —

Effect size Clear benefit

Citations / year ★★★★★

Authors

Dmitrieva N, Nagabukuro H, Resuehr D et al.

DOI 10.1016/j.pain.2010.08.037↗

Design: Präklinisch

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.

The impediment to action advances action. — Marcus Aurelius