title: Neurons in superficial trigeminal subnucleus caudalis responsive to oral cooling, menthol, and other irritant stimuli.
abstract: The recent discoveries of cold-sensitive transient receptor potential (TRP) channels prompted us to investigate the responses of neurons in trigeminal subnucleus caudalis (Vc) to intraoral cooling and agonists of TRPM8 and TRPA1. Single units responsive to lingual cooling were recorded in superficial laminae of Vc in thiopental-anesthetized rats. All units responded to noxious heat and 88% responded to menthol. Responses increased with menthol concentration from 0.1 to 1% (6.4-64 mM) and plateaued at 10% (640 mM). Noxious cold-evoked responses were significantly enhanced after menthol in a concentration-dependent manner. Constant-flow application of 1% menthol elicited a phasic discharge that adapted over 2-8 min and significantly enhanced subsequent cold-evoked but not heat-evoked responses; vehicle (10% ethanol) was ineffective. Reapplication of menthol 15 min later elicited a significantly reduced response (self-desensitization). Vc units were similarly excited phasically by 1% menthol dissolved in 40% ethanol. The 40% ethanol briefly excited Vc units during the first minute and reduced subsequent responses to noxious heat and cold while exhibiting neither self-desensitization nor cross-desensitization to menthol. Menthol cross-desensitized Vc responses to 40% ethanol. Most menthol-responsive units also responded to the TRPA1 agonists cinnamaldehyde and mustard oil, and the TRPV1 agonist capsaicin. Units in superficial Vc receive convergent input from primary afferents that express TRPM8, TRPA1, and/or TRPV1 channels, either directly or indirectly via intersubnuclear pathways. The convergent nature of these units suggests a general role in signaling noxious stimuli.
authors.affiliation: Section of Neurobiology, Physiology and Behavior, University of California-Davis, 1 Shields Ave., Davis, CA 95616, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Zanotto
authors.forename: Austin W
authors.initials: AW
authors.lastname: Merrill
authors.forename: Mirela Iodi
authors.initials: MI
authors.lastname: Carstens
authors.forename: E
authors.initials: E
authors.lastname: Carstens
mesh_terms: D000818:Animals; D017487:Ankyrins; D015220:Calcium Channels / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D000431:Ethanol / Q000494:pharmacology; D006358:Hot Temperature; D007509:Irritants / Q000494:pharmacology*; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D009055:Mouth / Q000294:innervation* / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors; D050051:Transient Receptor Potential Channels / Q000502:physiology; D014278:Trigeminal Nuclei / Q000166:cytology / Q000502:physiology*
chemical_list: D017487:Ankyrins; D015220:Calcium Channels; D002492:Central Nervous System Depressants; D007509:Irritants; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; D008610:Menthol; D000431:Ethanol