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.