[5][6] This protein is a member of the TRPV group of transient receptor potential family of ion channels.

[7] Fatty acid metabolites with affinity for this receptor are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA).

In primary afferent sensory neurons, it cooperates with TRPA1[9][10] (a chemical irritant receptor) to mediate the detection of noxious environmental stimuli.

[12] It is a nonselective cation channel that may be activated by a wide variety of exogenous and endogenous physical and chemical stimuli.

Its endogenous activators include: low pH (acidic conditions), the endocannabinoid anandamide, N-oleyl-dopamine, and N-arachidonoyl-dopamine.

Upon tissue damage and the consequent inflammation, a number of inflammatory mediators, such as various prostaglandins and bradykinin, are released.

[16] Various signaling pathways such as phosphorylation by PKA and PKC, interaction with calmodulin, dephosphorylation by calcineurin,[17] and the decrease of PIP2, have been implicated in the regulation of desensitization of TRPV1.

In the lab the receptor may be removed from mice giving them the inability to detect differences in ambient temperature.

Activation of TRPV1 modulates immune response including the release of inflammatory cytokines, chemokines, and the ability to phagocytose.

[18] Regarding innate immunity, activation of TRPV1 by capsaicin has been shown to suppress the production of nitrite radical, superoxide anion and hydrogen peroxide by macrophages.

In a mouse model, TRPV1 affect dendritic cell maturation and function, however, further studies are needed to clarify this effect in humans.

Activation of TRPV1 by capsaicin modulates neutrophil immune response due to the higher influx of calcium ions into the cell.

Multiple studies have proven that TRPV1 influences the outcome of several inflammatory diseases such as chronic asthma, esophageal inflammation, rheumatoid arthritis and cancer.

Significant importance should be paid to the confirmed expression of TRPV1 in microglia and astrocytes, cells found close to neurons.

The neuro-immune axis is the place of production of neuroinflammatory molecules and receptors that interplay between the two systems and ensure a complex response to external stimuli (or to the body's own pathologies).

TRPV1 antagonists have shown efficacy in reducing nociception from inflammatory and neuropathic pain models in rats.

Likewise, this explains the propensity of capsaicin (a TRPV1 agonist) to cause sweating (i.e.: a signal to reduce body temperature).

In a recent report, it was found that tonically active TRPV1 channels are present in the viscera and keep an ongoing suppressive effect on body temperature.

[31][32] As we increase understanding of modality specific agonism of TRPV1 it seems that next generation therapeutics targeting TRPV1 have the potential to side-step hyperthermia.

[38] Eight percent capsaicin patches have recently become available for clinical use, with supporting evidence demonstrating that a 30-minute treatment can provide up to 3 months analgesia by causing regression of TRPV1-containing neurons in the skin.

[39] Currently, these treatments must be re-administered on a regular (albeit infrequent) schedule in order to maintain their analgesic effects.

Although relatively weak agonists of TRPV1 in comparison to anandamide,[49] these linoleate metabolites have been proposed to act through TRPV1 in mediating pain perception in rodents[50][51][52] and to cause injury to airway epithelial cells and thereby to contribute to asthma disease[53] in mice and therefore possibly humans.

[61][62][63][64][65] N-Arachidonoyl dopamine, an endocannabinoid found in the human CNS, structurally similar to capsaicin, activates the TRPV1 channel with an EC50 of approximately of 50 nM.

[72] TRPV1 is also expressed at high levels in the central nervous system and has been proposed as a target for treatment not only of pain but also for other conditions such as anxiety.

Long-term depression and subsequent pruning of synapses with reduced activity is an important aspect of memory formation.

In rat brain slices, activation of TRPV1 with heat or capsaicin induced LTD while capsazepine blocked capsaicin's ability to induce LTD.[74] In the brainstem (solitary tract nucleus), TRPV1 controls the asynchronous and spontaneous release of glutamate from unmyelinated cranial visceral afferents - release processes that are active at normal temperatures and hence quite distinct from TRPV1 responses in painful heat.

TRPV1 has been shown to interact with: The dorsal root ganglion (DRG) neurons of mammals were known to express a heat-sensitive ion channel that could be activated by capsaicin.

After several rounds of screening and dividing the library, a single clone encoding the TRPV1 channel was finally identified in 1997.