3. PSYCHEDELICS’ANALGESIC MECHANISMS
Pain perception is a complex phenomenon involving somatosensory, cognitive, and affective components.26 Serotonergic signaling has been implicated in the peripheral and central mechanisms of nociceptive transmission and modulation in both acute and chronic pain states.27 Convergent preclinical and human findings support and strengthen the involvement of the 5-HT2A receptor in musculoskeletal pain perception, with relevance for clinical pain conditions. In addition, human studies have provided evidence for the involvement of 5-HT2A receptor in pain perception and processing. Associations have been found between the T102C polymorphism of the 5-HT2A receptor gene and fibromyalgia, and other genetic variations in 5-HT2A polymorphisms have been associated with chronic widespread pain.28,29 Psychedelics, through these serotonergic and other properties, hold promise as novel analgesics by modulating multiple dimensions of the pain experience.