TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization

Abstract

Cutaneous neurogenic inflammation (CNI) is inflammation that is induced (or enhanced) in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.

An Aliphatic Ester Diisopropyl Sebacate Exhibited an Adjuvant Effect on Fluorescein Isothiocyanate-Induced Contact Hypersensitivity Mouse Models

“…TRPA1 involvement in CHS and neurogenic inflammation in general is still a controversial issue. 15) In our experience, the enhanced skin sensitization to FITC in the presence of DBP 9) or DIPA 8) was inhibited by TRPA1-selective antagonist, HC-030031. We also observed that desensitization by the skin pretreatment with a strong TRPA1 agonist, allyl isothiocyanate, suppressed FITC-CHS.…”

“…Besides sensory neurons, TRPA1 is expressed on keratinocytes in the skin basal layer. 15) Although the expression of transient receptor potential vanilloid 1 channel on DC has been reported, 18) expression of TRPA1 on DC has not been established. 15) On the other hand, neuropeptides derived from sensory neurons are known to act on DC.…”

“…15) Although the expression of transient receptor potential vanilloid 1 channel on DC has been reported, 18) expression of TRPA1 on DC has not been established. 15) On the other hand, neuropeptides derived from sensory neurons are known to act on DC. 15) In the latter possibility, DIPS may stimulate TRPA1 on sensory neurons, which in turn release neuropeptides toward DC.…”

“…15) On the other hand, neuropeptides derived from sensory neurons are known to act on DC. 15) In the latter possibility, DIPS may stimulate TRPA1 on sensory neurons, which in turn release neuropeptides toward DC. DC activated with neuropeptides may initiate immune responses in the draining lymph nodes.…”

Mast cell‐neural interactions contribute to pain and itch

“…Neurogenic inflammation involves a multicellular system involving neurovascular interactions in the skin and visceral organs . It involves the release of vasoactive and pro‐inflammatory neuropeptides SP and calcitonin gene‐related peptide (CGRP) from the sensitized peripheral nerve endings; this leads to vascular dilatation, plasma extravasation, leukocyte infiltration, and mast cell activation .…”