title: Responses of intact and injured sural nerve fibers to cooling and menthol.
abstract: Intact and injured cutaneous C-fibers in the rat sural nerve are cold sensitive, heat sensitive, and/or mechanosensitive. Cold-sensitive fibers are either low-threshold type 1 cold sensitive or high-threshold type 2 cold sensitive. The hypothesis was tested, in intact and injured afferent nerve fibers, that low-threshold cold-sensitive afferent nerve fibers are activated by the transient receptor potential melastatin 8 (TRPM8) agonist menthol, whereas high-threshold cold-sensitive C-fibers and cold-insensitive afferent nerve fibers are menthol insensitive. In anesthetized rats, activity was recorded from afferent nerve fibers in strands isolated from the sural nerve, which was either intact or crushed 6-12 days before the experiment distal to the recording site. In all, 77 functionally identified afferent C-fibers (30 intact fibers, 47 injured fibers) and 34 functionally characterized A-fibers (11 intact fibers, 23 injured fibers) were tested for their responses to menthol applied to their receptive fields either in the skin (10 or 20%) or in the nerve (4 or 8 mM). Menthol activated all intact (n = 12) and 90% of injured (n = 20/22) type 1 cold-sensitive C-fibers; it activated no intact type 2 cold-sensitive C-fibers (n = 7) and 1/11 injured type 2 cold-sensitive C-fibers. Neither intact nor injured heat- and/or mechanosensitive cold-insensitive C-fibers (n = 25) and almost no A-fibers (n = 2/34) were activated by menthol. These results strongly argue that cutaneous type 1 cold-sensitive afferent fibers are nonnociceptive cold fibers that use the TRPM8 transduction channel.
authors.affiliation: Physiologisches Institut, Christian-Albrechts-Universität zu Kiel, Kiel, Germany; and.
authors.forename: Alina
authors.initials: A
authors.lastname: Teliban
authors.affiliation: Physiologisches Institut, Christian-Albrechts-Universität zu Kiel, Kiel, Germany; and.
authors.forename: Fabian
authors.initials: F
authors.lastname: Bartsch
authors.affiliation: Physiologisches Institut, Christian-Albrechts-Universität zu Kiel, Kiel, Germany; and.
authors.forename: Marek
authors.initials: M
authors.lastname: Struck
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Baron
authors.affiliation: Physiologisches Institut, Christian-Albrechts-Universität zu Kiel, Kiel, Germany; and w.janig@physiologie.uni-kiel.de.
authors.forename: Wilfrid
authors.initials: W
authors.lastname: Jänig
mesh_terms: D000758:Anesthesia; D000818:Animals; D003080:Cold Temperature; D004558:Electric Stimulation; D006358:Hot Temperature; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D008839:Microelectrodes; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D018373:Peripheral Nervous System Agents / Q000494:pharmacology*; D010812:Physical Stimulation; D017208:Rats, Wistar; D012879:Skin Physiological Phenomena / Q000187:drug effects; D013497:Sural Nerve / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology*; D050053:TRPM Cation Channels / Q000819:agonists / Q000378:metabolism; D013697:Thermosensing / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018373:Peripheral Nervous System Agents; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D008610:Menthol
keywords: cold sensitivity; cutaneous afferents; hairy skin; menthol; nerve injury; rat