The cloning of the first sensory Transient Receptor Potential (TRP) channel, TRPVanilloid 1 (TRPV1) in 1997, initiated a new era of pain research and coincided with the Decade of Pain Control and Research promulgated by the United States Congress. When cloned, TRPV1 channel was shown to be predominantly expressed in nociceptors (C- and A -fibers) and are activated by physical and chemical stimuli. Channel function can be amplified by transcriptional upregulation and posttranslational modification by proinflammatory agents. Indeed, TRPV1 gene disruption confirms that it is involved in transmitting inflammatory thermal hypersensitivity, but not acute thermal or mechanical pain sensitivity. Based on its distribution and functions, TRPV1 is considered as an ideal target for developing small molecule antagonists. Now, there is a growing body of evidence that TRPV1 is expressed in non-sensory neurons and non-neuronal cells. This raises the possibility of unwanted effects that may result from targeting TRPV1. A major consequence of TRPV1 blockade that has come to light in clinical trials following administration of antagonists is hyperthermia. This observation has threatened the abandonment of TRPV1 antagonists, although they are proven to be useful in certain modalities of pain. In this review, we will discuss the expression and functions of TRPV1 in various organ systems and highlight the consequences that might be associated with blocking the receptor.
Keywords: TRPV1, nociceptors, inflammatory mediators, pain, nociceptive ion channels, synaptic transmission, noxious stimuli, TRPV1 antagonists, resiniferatoxin, myentric ganglia, DRG neurons, TRPV1 mRNA, LNCaP, capsazepine, SB-366791, desensitization, nociceptive transmission, RTX treatment, Neurogenic inflammation, trigeminovascular system, CGRP, bradykinin, PGI2 prevention, myocardial ischemia, TRPV1 agonists, bladder hyperreflexia, RTX, BCTC, oleoylethanolamide, Parkinson's disease
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