The Emerging Role of TRP Channels in Mechanisms of Temperature and Pain Sensation

Abstract

Abstract:Pain is universal and vital to survival. It is an essential component of our sense of touch; together, touch and pain have evolved to enable our awareness of the intricacies of our environment and to warn us of danger and possible injury. There is a clear link between temperature sensation and pain-painful temperature sensations occur acutely and are a hallmark of inflammatory and chronic pain disorders of the nervous system. Mounting evidence suggests a subset of Transient Receptor Potential (TRP) ion channels activated by temperature (thermoTRPs) are important molecular players in acute, inflammatory and chronic pain states. Varying degrees of heat activate four of these channels (TRPV1-4), while cooling temperatures ranging from pleasant to painful activate two distantly related thermoTRP channels (TRPM8 and TRPA1). ThermoTRP channels are also chemosensitive, being activated and or modulated by plant-derived small molecules and endogenous inflammatory mediators. All thermoTRPs are expressed in tissues essential to cutaneous thermal and pain sensation. This review examines the contribution of thermoTRP channels to our understanding of temperature and pain transduction at the molecular level.Key Words: ThermoTRP, pain, DRG, skin, inflammation, TRPA1, TRPV. TRP CHANNELS: A PRIMERThe detection of temperature and pain stimuli is initiated at the level of primary afferent neurons that terminate as free nerve endings embedded in target tissues such as the dermal and epidermal layers of the skin, the oral and nasal mucosa and joints. The cell bodies of these neurons originate from cranial nerve ganglia and dorsal root ganglia (DRG). They relay information regarding environmental stimuli to the central nervous system via central processes projecting to the dorsal horn of the spinal cord. The conduction properties of neurons that respond to stimuli such as heat, cold and mechanical pressure are characteristic of C-and A fibers [91]. These neurons express the receptor tyrosine kinase trkA, are dependent on nerve growth factor (NGF) during development and are peptidergic, expressing nociceptive markers such as calcitonin gene-related peptide (CGRP) and substance P (SP) [121]. A portion of these neurons express c-ret postnatally, are dependent on glial-derived neurotrophic factor (GDNF) and are non-peptidergic. Instead they are distinguished by their ability to bind the plant lectin, isolectin-B4 (IB4) [95,133,164]. Until relatively recently, the mechanisms of how these sensory neurons detect thermal and pain stimuli were poorly understood.Caterina et al. achieved a breakthrough in our molecular understanding of thermal and pain sensation by identifying the "capsaicin receptor" [24]. Hot chili peppers produce this deterrent vanilloid molecule, which induces a burning sensation when coming in contact with mucous membranes of the mouth and eyes. This biological effect results from the excitation of a sub-population of nociceptive neurons [136] TRPV1 is the founding mammalian member of the superfamily of outwardly r...

Cooling of portable hand-held electronic devices using phase change materials in finned heat sinks

“…The thermosensory system was evaluated psychophysically by Greenspan et al [20] and their findings indicated that 45 C is the average threshold for heat. Story [21] suggested that Transient Receptor Potential (TRP) ion channels activated by temperature are important molecular players in acute inflammatory and chronic Table 3 Operation sequence of the heater in three operational modes.…”

TRP Channels and Pruritus

“…Besides cold, it is also activated by various, mostly pungent and/or irritant compounds such as botanical substances like mustard oil, delta-9-tetrahydrocannabinol, eugenol, gingerol, methyl salicylate, allyl isothiocyanate, cinnamaldehyde, formalin, and nicotine [312][313][314][315]. Like TRPV1, TRPA1 is also considered as a key player of transduction of painful stimuli and a potential target of analgesic therapies [316][317][318][319].…”

Mechanisms of myogenic response: Ca2+-dependent and -independent signaling

“…Because TRPM4 is Ca In addition to TRPC6 and TRPM4, the role of vanilloid family of TRP (TRPV) is also suggested in the mechanosensation of arteries (Liedtke et al, 2007). TRPV1-4 are originally known as heatsensitive NSC with differential ranges of threshold temperature for their activation (Story, 2006). Among the thermo-TRPV family, TRPV4 is also activated by osmotic stress (Phan et al, 2007), which might be associated with the mechanical stress during MR. Because MR requires physiological temperature, the putative role of TRPV in MR is worth of further investigation.…”