Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1.
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 approximately 42 degrees C to approximately 34 degrees 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.
Trevisani
M
M
Department of Experimental and Clinical Medicine, Headache Center, University of Ferrara, Via Fossato di Mortara 19, 44100 Ferrara, Italy.
Smart
D
D
Gunthorpe
M J
MJ
Tognetto
M
M
Barbieri
M
M
Campi
B
B
Amadesi
S
S
Gray
J
J
Jerman
J C
JC
Brough
S J
SJ
Owen
D
D
Smith
G D
GD
Randall
A D
AD
Harrison
S
S
Bianchi
A
A
Davis
J B
JB
Geppetti
P
P
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012684:Sensory Thresholds / Q000187:drug effects; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels; D013823:Thermoreceptors / Q000187:drug effects / Q000502:physiology; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects
D011955:Receptors, Drug; D011994:Recombinant Proteins; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D013373:Substance P; D000431:Ethanol; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin