Abstract
Pain is the most common manifestation of both acute and chronic inflammation that often challenges patients with rheumatic disease. Simply, we attribute this to local joint changes of pH in joints, the formation of radicals, enhanced joint pressure, or cytokine release acting on local nerves to produce pain. However, there is a more complex interplay of interactions between cytokines, mediators of inflammation, and ion channels that influence the final immune response and our perception of pain. Endocannabinoids, a group of less well-known endogenous bioactive lipids, have such manifold immunomodulatory effects able to influence both inflammation and pain. In this review, we overview the endocannabinoid system, its role in pain, inflammation, and immune regulation, and highlight the emerging challenges and therapeutic hopes.