Neuronal and ion channel mechanisms of noxious heat sensing in mammals: A puzzle of sensory physiology and pharmacology
Pethő G, Reeh P (2026)
Publication Type: Journal article, Review article
Publication year: 2026
Journal
DOI: 10.1111/bph.70525
Abstract
Transient receptor potential vanilloid 1 (TRPV1) was the first noxious heat-sensitive channel discovered. In rodents, its role is robust in the heat response of the cell body of polymodal nociceptors, but surprisingly small in that of the peripheral terminals in the skin. TRPV1's contribution to the heat threshold depends on anatomical localisation, being prevalent in the tail while absent in the hind paw of the mouse. In behavioural tests of rodents, the role of TRPV1 is marginal with lower, but significant with higher, temperatures. In contrast to the basal heat response, inflammatory heat hyperalgesia/allodynia critically depends on TRPV1. In contrast to rats and mice, TRPV1 receptor antagonists elevate the heat pain threshold in humans, potentially leading to scald injuries and precluding their clinical use. TRPM3 and anoctamin 1 are other heat-sensitive channels that play limited roles in rodents' noxious heat responsiveness. The function of the cold- and heat-activated TRPA1 channel in heat sensation is a matter of debate. In contrast, TRPV2, TRPV3, TRPV4 and TRPM2 channels are unlikely to be major determinants of noxious heat sensation. Combined genetic ablation of TRPV1, TRPA1 and TRPM3 in the mouse results in a near-complete reduction of the heat response; however, the heat threshold remains unchanged. In humans, however, combined pharmacological block of the three TRP channels elevates the noxious heat threshold in skin by only 1°C. TRPV1 appears to be the only known heat sensor with an established but limited role in heat pain sensation; thus, other heat sensor must also contribute.
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APA:
Pethő, G., & Reeh, P. (2026). Neuronal and ion channel mechanisms of noxious heat sensing in mammals: A puzzle of sensory physiology and pharmacology. British Journal of Pharmacology. https://doi.org/10.1111/bph.70525
MLA:
Pethő, Gábor, and Peter Reeh. "Neuronal and ion channel mechanisms of noxious heat sensing in mammals: A puzzle of sensory physiology and pharmacology." British Journal of Pharmacology (2026).
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