3.1 Modulation of bottom-up nociception
The somatosensory dimension of pain encompasses its intensity, quality, and spatial characteristics.30 Mechanistic studies have demonstrated that 5-HT2A receptors are involved in the nociceptive transmission through the spinal cord31 and that their activation can inhibit the descending nociceptive transmission in states of chronic and neuropathic pain.27,32,33 5-HT2A receptors are expressed in neurons in the dorsal root ganglia (DRG), nodule-like structures found on the posterior root of each spinal nerve, among other locations, which contain the cell bodies or afferent sensory neurons carrying pain signals back to the central nervous system (CNS). Therefore, the DRG are critical structures responsible for central pain sensitization, a mechanism by which the CNS becomes sensitized to nociceptive stimuli, promoting the maintenance of chronic pain states. Some of the analgesic properties of psilocybin, for instance, are believed to be mediated by downregulation of 5-HT2A receptor in the DRG.34,35 This downregulation may counteract central pain sensitization.