TRPA1 and Substance P Mediate Colitis in Mice

Methylglyoxal Activates Nociceptors through Transient Receptor Potential Channel A1 (TRPA1)

“…As it is activated by hypoxia (15), CO 2 (16), lactic acid (17), and mediators of oxidative stress (18) and inflammation (19,20), TRPA1 has increasingly emerged as relevant for nociception and pain in pathophysiological conditions. Recent studies also indicate that TRPA1 may be a promising target for treatment of airway inflammation (21), colitis (22), and diabetes (23,24).…”

Highlights in inflammatory bowel disease – from bench to bedside

“…However, the peptidergic subpopulation of these nerve fi bers releases neuropeptides, as a result of antidromic activation of peripheral nerve terminals (55) . The two major " sensory " neuropeptides -calcitonin gene-related peptide (CGRP) and substance P (SP) -have been shown to be the critical link between the sensory nervous and the immune systems (55,56) . Pharmacological blockage of the SP receptor neurokinin (NK)1 was benefi cial in TNBS and DSS colitis (57,58) .…”

The role of TRPA1 in visceral inflammation and pain

“…[23][24][25][26][27] Subsequent to TRPA1 activation, increases in intracellular Ca 2+ induce the peripheral release of neuropeptides (substance P and calcitonin gene-related peptide (CGRP)), purines, and other transmitters from sensitized nerve fiber endings, which ultimately results in neurogenic inflammation and hypersensitivity. [28][29][30][31] It is interesting to note that Ca 2+ does not only represent an intermediate player in TRPA1-mediated events, but also acts as a direct modulator of TRPA1 activity. Indeed, electrophysiological recordings have demonstrated an increase in TRPA1 activity during Ca 2+ perfusion in vitro.…”

“…28 This inflammatory response, along with the release of substance P and CGRP from sensitized nerve fiber endings, contributes to the development of visceral hypersensitivity. [28][29][30][31] A few years ago, Yang et al demonstrated that reduction of TRPA1 expression by antisense oligodeoxynucleotide significantly reduced colonic hypersensitivity induced by trinitrobenzene-sulphonic acid (TNBS)-mediated colitis in mice. 48 These results were further supported and expanded by a recent study showing that TRPA1 agonists allyl isothiocyanate and trans-cinnamaldehyde induced mechanosensory responses in vagal and pelvic serosal afferents of TRPA1 +/+ mice, but not in TRPA1-deficient animals.…”

“…Indeed, several experimental models of colitis have demonstrated the efficacy of mustard oil in inducing colitis. [28][29][30][31] Mustard oil-induced colitis is characterized by the upregulation of several pro inflammatory mediators including interleukin (IL)-1β, IL-6, granulocyte macrophage colony stimulating factor (GM-CSF), macrophage chemotactic protein 1 (MCP-1) and macrophage inflammatory …”