title: Botulinum toxin-A treatment reduces human mechanical pain sensitivity and mechanotransduction.
abstract: The mechanisms underlying the analgesic effects of botulinum toxin serotype A (BoNT-A) are not well understood. We have tested the hypothesis that BoNT-A can block nociceptor transduction. Intradermal administration of BoNT-A to healthy volunteers produced a marked and specific decrease in noxious mechanical pain sensitivity, whereas sensitivity to low-threshold mechanical and thermal stimuli was unchanged. BoNT-A did not affect cutaneous innervation. In cultured rodent primary sensory neurons, BoNT-A decreased the proportion of neurons expressing slowly adapting mechanically gated currents linked to mechanical pain transduction. Inhibition of mechanotransduction provides a novel locus of action of BoNT-A, further understanding of which may extend its use as an analgesic agent.
authors.affiliation: Wolfson Centre for Age-Related Disease, King's College London, London.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Paterson
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lolignier
authors.forename: John N
authors.initials: JN
authors.lastname: Wood
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
authors.forename: David L H
authors.initials: DL
authors.lastname: Bennett
mesh_terms: D000328:Adult; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology* / Q000627:therapeutic use*; D002478:Cells, Cultured; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D064368:Healthy Volunteers; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D009465:Neuromuscular Agents / Q000494:pharmacology / Q000627:therapeutic use; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011601:Psychophysics; D011984:Sensory Receptor Cells / Q000187:drug effects; D055815:Young Adult
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A