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Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1

Abstract

The vanilloid receptor-1 (VR1) is a heat-gated ion channel that is responsible for the burning sensation elicited by capsaicin. A similar sensation is reported by patients with esophagitis when they consume alcoholic beverages or are administered alcohol by injection as a medical treatment. We report here that ethanol activates primary sensory neurons, resulting in neuropeptide release or plasma extravasation in the esophagus, spinal cord or skin. Sensory neurons from trigeminal or dorsal root ganglia as well as VR1-expressing HEK293 cells responded to ethanol in a concentration-dependent and capsazepine-sensitive fashion. Ethanol potentiated the response of VR1 to capsaicin, protons and heat and lowered the threshold for heat activation of VR1 from 42°C to 34°C. This provides a likely mechanistic explanation for the ethanol-induced sensory responses that occur at body temperature and for the sensitivity of inflamed tissues to ethanol, such as might be found in esophagitis, neuralgia or wounds.

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Figure 1: Ethanol-induced neurotransmitter release and plasma extravasation.
Figure 2: Ethanol stimulates and potentiates native and recombinant VR1 responses.
Figure 3: Ethanol modulates capsaicin-, anandamide- or proton-gated inward currents recorded from hVR1-expressing HEK293 cells.
Figure 4: Ethanol shifts the threshold for VR1 heat activation.

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Acknowledgements

We thank C. Farrant and S. Lomax for preparation of artwork. This work was supported in part by ARCA (Padua) and Cofin (MIUIR, Rome).

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Correspondence to J B. Davis.

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Trevisani, M., Smart, D., Gunthorpe, M. et al. Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1. Nat Neurosci 5, 546–551 (2002). https://doi.org/10.1038/nn0602-852

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