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Pharmaceuticals 2016, 9(4), 72; doi:10.3390/ph9040072

Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies

1
Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA
2
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA
3
Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA
4
Siteman Cancer Center, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Arpad Szallasi and Susan M. Huang
Received: 24 August 2016 / Revised: 7 November 2016 / Accepted: 9 November 2016 / Published: 14 November 2016
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Abstract

Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these TRP channels are also expressed in neurons of the central nervous system, and in non-neuronal cells that communicate with sensory nerves. Nociceptive TRPs are activated by specific physico-chemical stimuli to provide the excitatory trigger in neurons. In addition, decades of research has identified a large number of immune and neuromodulators as mediators of nociceptive TRP channel activation during injury, inflammatory and other pathological conditions. These findings have led to aggressive targeting of TRP channels for the development of new-generation analgesics. This review summarizes the complex activation and/or modulation of nociceptive TRP channels under pathophysiological conditions, and how these changes underlie acute and chronic pain conditions. Furthermore, development of small-molecule antagonists for several TRP channels as analgesics, and the positive and negative outcomes of these drugs in clinical trials are discussed. Understanding the diverse functional and modulatory properties of nociceptive TRP channels is critical to function-based drug targeting for the development of evidence-based and efficacious new generation analgesics. View Full-Text
Keywords: TRP channel; pain; nociception; inflammatory pain; neuropathic pain; visceral pain; cancer pain; migraine; dental pain; peripheral sensitization TRP channel; pain; nociception; inflammatory pain; neuropathic pain; visceral pain; cancer pain; migraine; dental pain; peripheral sensitization
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mickle, A.D.; Shepherd, A.J.; Mohapatra, D.P. Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies. Pharmaceuticals 2016, 9, 72.

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