TRPA1 ion channel in the spinal dorsal horn as a therapeutic target in central pain hypersensitivity and cutaneous neurogenic inflammation

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective, calcium permeable cation channel expressed by a subpopulation of primary afferent nociceptive nerve fibers. On peripheral nerve endings, TRPA1 channel contributes to transduction of chemical and physical stimuli, whereas on the central endings in the spinal dorsal horn, which is the topic of this brief review, it regulates glutamatergic transmission. Blockade of the spinal TRPA1 channel has attenuated mechanical pain hypersensitivity particularly to low-intensity stimulation in various pathophysiological conditions, whereas blockade of the TRPA1 channel-mediated regulation of transmission failed to influence baseline pain behavior in healthy control animals. Additionally, blockade of the spinal TRPA1 channel reduced cutaneous neurogenic inflammation, presumably by decreasing drive of spinal interneurons that induce a proinflammatory dorsal root reflex. The spinal TRPA1 channel provides a promising target for development of a selective disease-modifying therapy for central pain hypersensitivity. Blockade of the spinal TRPA1 channel-mediated regulation of transmission may also attenuate cutaneous neurogenic inflammation.