[9] One of the specific functions of this protein studies involves a role in the detection, integration and initiation of pain signals in the peripheral nervous system.

[11] Recent studies indicate that TRPA1 is activated by a number of reactive [8][12] (cinnamaldehyde, farnesyl thiosalicylic acid, formalin, hydrogen peroxide, 4-hydroxynonenal, acrolein, and tear gases[13][14][15]) and non-reactive compounds (nicotine,[16] PF-4840154[17]) and is thus considered as a "chemosensor" in the body.

[19] This sub-population of peripheral C-fibers is considered important sensors of nociception in humans and their activation will under normal conditions give rise to pain.

This work revealed that the channel assembles as a homotetramer, and possesses several structural features that hint at its complex regulation by irritants, cytoplasmic second messengers (e.g., calcium), cellular co-factors (e.g., inorganic anions like polyphosphates), and lipids (e.g., PIP2).

[27] Breakthrough research combining cryo-electron microscopy and electrophysiology later elucidated the molecular mechanism of how the channel functions as a broad-spectrum irritant detector.

Upon covalent attachment, the allosteric nexus adopts a conformational change that is propagated to the channel's pore, dilating it to permit cation influx and subsequent cellular depolarization.

A family from Colombia suffers from debilitating upper-body pain starting in infancy that is usually triggered by fasting or fatigue (illness, cold temperature, and physical exertion being contributory factors).

[33] Oxalate, a metabolite of an anti cancer drug oxaliplatin, has been demonstrated to inhibit prolyl hydroxylase, which endows cold-insensitive human TRPA1 with pseudo cold sensitivity (via reactive oxygen generation from mitochondria).

[34] TRPA1 can be considered to be one of the most promiscuous TRP ion channels, as it seems to be activated by a large number of noxious chemicals found in many plants, food, cosmetics and pollutants.

While the earliest inhibitors, such as HC-030031, were lower potency (micromolar inhibition) and had limited TRPA1 specificity, the more recent discovery of highly potent inhibitors with low nanomolar inhibition constants, such as A-967079 and ALGX-2542 as well as high selectivity among other members the TRP superfamily and lack of interaction with other targets have provided valuable tool compounds and candidates for future drug development.

They are members of the specialized proresolving mediators (SPMs) class of metabolites that function to resolve diverse inflammatory reactions and diseases in animal models and, it is proposed, in humans.