Abstract
In mammals, TRPA1 is the sole member of the TRPA gene subfamily. Recent reports identified TRPA1 as a target for the noxious and inflammatory irritant mustard oil in peripheral sensory neurons, implicating a functional role in pain and neurogenic inflammation. Other studies suggest that TRPA1 participates in additional sensory processes, such as cold sensation and hearing. In this chapter, we summarize and discuss these recent findings and speculate about the potential physiological role of TRPA1 in chemosensation and pain transduction.
Introduction
TRPA1 is a member of the TRPA branch of the TRP ion channel gene family. On the structural level, TRPA channels are characterized by multiple N-terminal ankyrin repeats (~14 in the N-terminus of human TRPA1). Superficially, TRPA channels resemble TRPN channels that were implicated in mechanotransduction and hearing. However, the ion channel domain of TRPA channels is evolutionary distant. While others express two or more TRPA genes, mammals have only a sole TRPA gene, TRPA1. Far from having only a rudimentary presence, TRPA1 has attracted significant attention from different areas of sensory research. In mammals, TRPA1 is expressed in a subset of peripheral sensory neurons, implicating a specialized role in sensory transduction. Recent studies found evidence that TRPA1 is involved in sensory neural responses to mustard oil and other chemical irritants. Moreover, TRPA1 may serve as a sensor for noxious cold temperature. Other studies identified TRPA1 as a candidate for the auditory hair cell transduction channel. Here, we focus on TRPA1 as a target for chemical sensory irritants and discuss its physiological role in acute and inflammatory pain.
Conclusion
The studies show TRPA1 channels in mammalian sensory neurons contribute to acute and inflammatory pain. TRPA1 is activated downstream of inflammatory PLC-coupled receptors for proalgesic agents/etc in vivo and acts in concert with TRPV1 to cause thermal hyperalgesia. Whether endogenous ligands for TRPA1 exist remains to be documented. The sensitivity of TRPA1 to phytocannabinoids indicates that endogenous cannabinoid-like ligands may modulate TRPA1 function. While it is not known whether mustard oil–like compounds are endogenously expressed in mammals, other endogenous organosulfur compounds could affect the TRPA1 activity. Future pharmacological, electrophysiological, and genetic studies are needed to clarify these and other aspects of TRPA1 function. In addition to TRPV1, TRPA1 represents an exciting new target for the development of potential new analgesics and anti-inflammatory agents.
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