title: The putative role of vanilloid receptor-like protein-1 in mediating high threshold noxious heat-sensitivity in rat cultured primary sensory neurons.
abstract: High threshold noxious heat-activated currents and vanilloid receptor-like protein-1 expression were studied in rat cultured primary sensory neurons to find out the molecule(s) responsible for high threshold noxious heat-sensitivity. The average temperature threshold and amplitude of high threshold noxious heat-activated currents were 51.6 +/- 0.13 degrees C and -2.0 +/- 0.1nA (at a holding potential of -60 mV), respectively. The current-voltage relationship of high threshold noxious heat-activated currents was linear at positive membrane potentials, while it showed a weak inward rectification at negative membrane potentials. The average reversal potential measured in control intracellular and extracellular solutions was 4.5 +/- 0.9 mV (n = 6). Ionic substitutions revealed that the high threshold noxious heat-activated current is a nonselective cationic current with calculated ionic permeabilities of Cs+ : Na+ : Ca2+ (1 : 1.3 : 4.5). Consecutive stimuli reduced the heat threshold from 52.2 +/- 1 to 48.4 +/- 1.4 degrees C and then to 44 +/- 0.7 degrees C (n = 3). High threshold noxious heat-activated currents could dose-dependently and reversibly be reduced by ruthenium red (100 nm-10 micro m) but not by capsazepine (10 micro m). The average longest diameter of high threshold noxious heat-sensitive neurons was 31.48 +/- 0.5 micro m (A = approximately 778 micro m2; n = 77). Twenty-three percent of the total neuronal population expressed vanilloid receptor-like protein-1. The average area of the vanilloid receptor-like protein-1-immunopositive cells was 1,696 +/- 65.3 micro m2 (d = approximately 46 micro m). Vanilloid receptor-like protein-1-expressing neurons did not express the vanilloid receptor 1. Comparison of our data with results obtained in vanilloid receptor-like protein-1-expressing non-neuronal cells and previous immunohistochemical findings suggests that high threshold noxious heat-activated currents are produced by vanilloid receptor-like protein-1 and that high threshold heat-sensitive dorsal root ganglion neurons are the perikarya of type I noxious heat-sensitive fibers.
authors.affiliation: Department of Anaesthetics and Intensive Care, Imperial College, Faculty of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
authors.forename: Jatinder
authors.initials: J
authors.lastname: Ahluwalia
authors.forename: Humphrey
authors.initials: H
authors.lastname: Rang
authors.forename: Istvan
authors.initials: I
authors.lastname: Nagy
mesh_terms: D000344:Afferent Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006358:Hot Temperature / Q000009:adverse effects; D007150:Immunohistochemistry; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012430:Ruthenium Red / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D050916:TRPV Cation Channels; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology*
chemical_list: D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D012430:Ruthenium Red; C071423:capsazepine; D002211:Capsaicin