title: A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers.
abstract: Desensitization of nociceptive sensory nerve endings is the basis for the therapeutic use of capsaicin in neuropathic pain syndromes. This study evaluated the pharmacodynamic effects of a single 60-minute application of NGX-4010, a high-concentration (8% w/w) capsaicin patch, on both thighs of healthy volunteers. Epidermal nerve fiber (ENF) density and quantitative sensory testing (QST) using thermal, tactile, and sharp mechanical-pain (pinprick) stimuli were evaluated 1, 12 and 24 weeks after capsaicin exposure. After 1 week, there was about an 80% reduction of ENF density compared to unexposed sites. In addition, there was about an 8% increase in tactile thresholds compared to baseline and the proportion of stimuli reported as sharp mechanical pain decreased by about 15 percentage points. Twelve weeks after exposure to capsaicin, ENF regeneration was evident, but not complete, and sharp mechanical-pain sensation and tactile thresholds did not differ from unexposed sites. Nearly full (93%) ENF recovery was observed at 24 weeks. No statistically significant changes in heat- or cold-detection thresholds were observed at any time point. NGX-4010 was generally well tolerated. Transient, mild warming or burning sensations at the site of application were common adverse effects.
  
  
  CONCLUSIONS
  This article evaluates the effect of a single 60-minute NGX-4010 application on ENF density and QST in healthy volunteers followed for 24 weeks. The results help predict the long-term safety of NGX-4010 applications in patients.
authors.affiliation: Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455, USA. kenne001@umn.edu
authors.forename: William R
authors.initials: WR
authors.lastname: Kennedy
authors.forename: Geertrui F
authors.initials: GF
authors.lastname: Vanhove
authors.forename: Shiao-Ping
authors.initials: SP
authors.lastname: Lu
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Tobias
authors.forename: Keith R
authors.initials: KR
authors.lastname: Bley
authors.forename: David
authors.initials: D
authors.lastname: Walk
authors.forename: Gwen
authors.initials: G
authors.lastname: Wendelschafer-Crabb
authors.forename: Donald A
authors.initials: DA
authors.lastname: Simone
authors.forename: Mona M
authors.initials: MM
authors.lastname: Selim
mesh_terms: D000293:Adolescent; D000328:Adult; D002211:Capsaicin / Q000008:administration & dosage / Q000633:toxicity*; D003080:Cold Temperature; D004817:Epidermis / Q000187:drug effects* / Q000294:innervation*; D005260:Female; D006304:Health Status; D006358:Hot Temperature; D006801:Humans; D008297:Male; D009416:Nerve Regeneration; D017288:Pain Threshold / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010812:Physical Stimulation; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018689:Sensory System Agents / Q000008:administration & dosage / Q000633:toxicity*; D012684:Sensory Thresholds / Q000187:drug effects; D013997:Time Factors; D055815:Young Adult
chemical_list: D018689:Sensory System Agents; D002211:Capsaicin