title: Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial.
abstract: BACKGROUND
  Capsaicin specifically activates, and then gradually exhausts, the transient receptor potential vanilloid type 1 (TRPV1) receptor, a key receptor in neuropathic pain. Activation of the TRPV-1 receptor is accompanied by burning pain. A natural substance or medication that can reduce the burning pain resulting from capsaicin application may have therapeutic potential in neuropathic pain.
  
  
  OBJECTIVE
  To assess the pain-relieving effects of a mannitol-containing cream in a capsaicin-based pain model.
  
  
  METHODS
  Randomized, placebo-controlled, double-blind clinical trial.
  
  
  METHODS
  Outpatient pain clinic.
  
  
  METHODS
  Twenty-five adults with pain-free lips.
  
  
  METHODS
  Capsaicin .075% cream was applied to both halves of each participant's upper lip, inducing pain via stimulation of the transient receptor potential vanilloid 1 (TRPV1, capsaicin) receptor, then removed after 5 minutes or when participants reported a burning pain of 8/10, whichever came first. A cream containing mannitol and the same cream without mannitol (control) were then immediately applied, 1 on each side of the lip, in an allocation-masked manner.
  
  
  METHODS
  Participants self-recorded a numeric rating scale (NRS, 0-10) pain score for each side of the lip per minute for 10 minutes. A t-test was performed to evaluate the pain score change from baseline between each side of the lip at each recording. Area under the curve (AUC) analysis was used to determine the overall difference between groups.
  
  
  RESULTS
  Participants reached a capsaicin-induced pain level of 7.8 ± 1.0 points in 3.3 ± 1.6 minutes that was equal on both sides of the lip. Both groups reported progressive diminution of pain over the 10-minute study period. However, participants reported significantly reduced pain scores on the mannitol cream half-lip compared to control at 3 through 10 minutes (P < .05) and in AUC analysis (P < .001).
  
  
  CONCLUSIONS
  Mannitol cream reduced self-reported pain scores in a capsaicin pain model more rapidly than a control cream, potentially via a TRPV1 receptor effect.
authors.affiliation: University of British Columbia, North Vancouver, BC, Canada.
authors.forename: Helene
authors.initials: H
authors.lastname: Bertrand
authors.affiliation: University of British Columbia, Faculty of Pharmaceutical Sciences, North Vancouver, BC, Canada.
authors.forename: Marylene
authors.initials: M
authors.lastname: Kyriazis
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Kansas, Kansas City, KS.
authors.forename: K Dean
authors.initials: KD
authors.lastname: Reeves
authors.affiliation: Private Practice Sports Medicine, retired, Cass Bass, Lyttelton, New Zealand.
authors.forename: John
authors.initials: J
authors.lastname: Lyftogt
authors.affiliation: Department of Family Medicine, University of Wisconsin, Madison, WI.
authors.forename: David
authors.initials: D
authors.lastname: Rabago
mesh_terms: D059787:Acute Pain / Q000188:drug therapy* / Q000209:etiology*; D000287:Administration, Topical; D000328:Adult; D000368:Aged; D002211:Capsaicin; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008046:Lip; D008297:Male; D008353:Mannitol / Q000008:administration & dosage*; D008875:Middle Aged; D010147:Pain Measurement; D010865:Pilot Projects; D063465:Skin Cream; D013549:Sweetening Agents / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D013549:Sweetening Agents; D008353:Mannitol; D002211:Capsaicin