title: The cell and molecular basis of mechanical, cold, and inflammatory pain.
abstract: Peripheral pain pathways are activated by a range of stimuli. We used diphtheria toxin to kill all mouse postmitotic sensory neurons expressing the sodium channel Nav1.8. Mice showed normal motor activity and low-threshold mechanical and acute noxious heat responses but did not respond to noxious mechanical pressure or cold. They also showed a loss of enhanced pain responses and spontaneous pain behavior upon treatment with inflammatory insults. In contrast, nerve injury led to heightened pain sensitivity to thermal and mechanical stimuli indistinguishable from that seen with normal littermates. Pain behavior correlates well with central input from sensory neurons measured electrophysiologically in vivo. These data demonstrate that Na(v)1.8-expressing neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing.
authors.affiliation: Molecular Nociception Group, University College London (UCL), Gower Street, London, WC1E 6BT, UK.
authors.forename: Bjarke
authors.initials: B
authors.lastname: Abrahamsen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Curtis O
authors.initials: CO
authors.lastname: Asante
authors.forename: Cruz Miguel
authors.initials: CM
authors.lastname: Cendan
authors.forename: Steve
authors.initials: S
authors.lastname: Marsh
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Martinez-Barbera
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Nassar
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Dickenson
authors.forename: John N
authors.initials: JN
authors.lastname: Wood
mesh_terms: D000818:Animals; D003080:Cold Temperature; D004594:Electrophysiology; D005620:Freund's Adjuvant; D006358:Hot Temperature; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold; D011312:Pressure; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D005620:Freund's Adjuvant