title: Phenotyping the function of TRPV1-expressing sensory neurons by targeted axonal silencing.
abstract: Specific somatosensations may be processed by different subsets of primary afferents. C-fibers expressing heat-sensitive TRPV1 channels are proposed, for example, to be heat but not mechanical pain detectors. To phenotype in rats the sensory function of TRPV1(+) afferents, we rapidly and selectively silenced only their activity, by introducing the membrane-impermeant sodium channel blocker QX-314 into these axons via the TRPV1 channel pore. Using tandem mass spectrometry we show that upon activation with capsaicin, QX-314 selectively accumulates in the cytosol only of TRPV1-expressing cells, and not in control cells. Exposure to QX-314 and capsaicin induces in small DRG neurons a robust sodium current block within 30 s. In sciatic nerves, application of extracellular QX-314 with capsaicin persistently reduces C-fiber but not A-fiber compound action potentials and this effect does not occur in TRPV1(-/-) mice. Behavioral phenotyping after selectively silencing TRPV1(+) sciatic nerve axons by perineural injections of QX-314 and capsaicin reveals deficits in heat and mechanical pressure but not pinprick or light touch perception. The response to intraplantar capsaicin is substantially reduced, as expected. During inflammation, silencing TRPV1(+) axons abolishes heat, mechanical, and cold hyperalgesia but tactile and cold allodynia remain following peripheral nerve injury. These results indicate that TRPV1-expressing sensory neurons process particular thermal and mechanical somatosensations, and that the sensory channels activated by mechanical and cold stimuli to produce pain in naive/inflamed rats differ from those in animals after peripheral nerve injury.
authors.affiliation: F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Brenneis
authors.forename: Katrin
authors.initials: K
authors.lastname: Kistner
authors.forename: Michelino
authors.initials: M
authors.lastname: Puopolo
authors.forename: David
authors.initials: D
authors.lastname: Segal
authors.forename: David
authors.initials: D
authors.lastname: Roberson
authors.forename: Marco
authors.initials: M
authors.lastname: Sisignano
authors.forename: Sandra
authors.initials: S
authors.lastname: Labocha
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreirós
authors.forename: Amanda
authors.initials: A
authors.lastname: Strominger
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Cobos
authors.forename: Nader
authors.initials: N
authors.lastname: Ghasemlou
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.forename: Peter W
authors.initials: PW
authors.lastname: Reeh
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Bean
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D059350:Chronic Pain / Q000503:physiopathology*; D004195:Disease Models, Animal; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology*
chemical_list: D000779:Anesthetics, Local; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C012647:QX-314; D008012:Lidocaine; D002211:Capsaicin