title: Short lasting transient effects of a capsaicin 8% patch on nociceptor activation in humans.
abstract: At high concentration, the TRPV-1 agonist capsaicin de-sensitizes nociceptors and reduces the intra-epidermal nerve density.
  
  
  
  We investigated the effects of a 5 × 10 cm capsaicin 8% patch on C- and A-delta-nociceptor activation in ten healthy subjects before and at days 1-3-7-21 after patch application. Thermal thresholds, infrared thulium-YAG laser-evoked potentials (LEP) and heat pain (numeric rating scale, NRS, 0-10), electrically induced pain (10 pulses, 1.5-fold pain threshold intensity, five randomized series of 5-10-20-50-100 Hz), and axon-reflex flare (laser Doppler imaging) were recorded.
  
  
  
  Thermal hypoesthesia developed upon capsaicin 8% treatment. Warmth detection thresholds increased at day 1-3, heat pain thresholds were increased by about 2.6 °C after day 3, and laser-evoked heat pain remained significantly reduced for 7 days. Axon-reflex flare responses (days 1-3), but not supra-threshold electrically induced pain were significantly reduced by the capsaicin patch.
  
  
  
  Axonal nociceptor function assessed by electrical excitability tests supplements threshold tests of nociceptive endings. The differential analgesic effects of 8% capsaicin patches may be attributed to the kinetics of capsaicin and the different depth of nociceptive nerve fibres, yet, the time course does not match the long-lasting analgesia observed in neuropathic pain patients treated with the same patch. WHAT DOES THIS STUDY ADD?: Axonal nociceptor function assessed by supra-threshold electrical excitability tests did not coincide with capsaicin-induced transduction changes supplementing threshold measures of terminal nociceptor endings. Threshold measurements do not reflect the sustained effect of pain relief seen in neuropathic pain patients. Capsaicin-sensitive nociceptors responsible for spontaneous pain are either not specifically tested with currently available sensory stimulation protocols or have higher capsaicin sensitivity or slower recovery under neuropathic conditions.
authors.affiliation: Centre for Pain Medicine, Swiss Paraplegic Centre, Nottwil, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Landmann
authors.affiliation: Centre for Pain Medicine, Swiss Paraplegic Centre, Nottwil, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Lustenberger
authors.affiliation: Centre for Pain Medicine, Swiss Paraplegic Centre, Nottwil, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Schleinzer
authors.affiliation: University Medicine Mannheim, Department of Anesthesiology and Intensive Care Medicine, University of Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmelz
authors.affiliation: Centre for Pain Medicine, Swiss Paraplegic Centre, Nottwil, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Stockinger
authors.affiliation: University Medicine Mannheim, Department of Anesthesiology and Intensive Care Medicine, University of Heidelberg, Germany. roman.rukwied@medma.uni-heidelberg.de.
authors.forename: R
authors.initials: R
authors.lastname: Rukwied
mesh_terms: D000328:Adult; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066331:Laser-Evoked Potentials / Q000187:drug effects*; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects*; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects*
chemical_list: D002211:Capsaicin