Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options

Challenges in the management of ocular pain are an underappreciated topic. Currently available therapeutics lack both efficacy and clear guidelines for their use, with many also possessing unacceptable side effects. Promising novel agents would offer analgesic, anti-inflammatory, and possibly neuroprotective actions; have favorable ocular safety profiles; and show potential in managing neuropathic pain. Growing evidence supports a link between the endocannabinoid system (ECS) and a range of physiological and disease processes, notably those involving inflammation and pain. Both preclinical and clinical data suggest analgesic and anti-inflammatory actions of cannabinoids and ECS-modifying drugs in chronic pain conditions, including those of neuropathic origin. This review will examine existing evidence for the anatomical and physiological basis of ocular pain, specifically, ocular surface disease and the development of chronic ocular pain. The mechanism of action, efficacy, and limitations of currently available treatments will be discussed, and current knowledge related to ECS-modulation of ocular pain and inflammatory disease will be summarized. A perspective will be provided on the future directions of ECS research in terms of developing cannabinoid therapeutics for ocular pain.