Influence of thermode size for detecting heat pain dysfunction in a capsaicin model of epidermal nerve fiber loss

Nidal Khalili, Gwen Wendelschafer-Crabb, William R. Kennedy, Donald A. Simone

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Quantitative sensory testing of heat pain sensation has become an important tool to evaluate small caliber afferent nerve function in peripheral neuropathy. In earlier studies, we found that topical application of capsaicin in humans results in the loss of epidermal nerve fibers (ENFs) with a corresponding decrease in detection of heat pain sensation. Capsaicin may therefore be a useful model for developing optimal psychophysical testing procedures for detection of neuropathy in its early stages. Here we determined the influence of thermal probe (thermode) size in detecting the diminished heat pain sensation following capsaicin application. Twelve healthy volunteers applied 0.075% capsaicin topically to the volar forearm four times daily for 7 days. Psychophysical measures of heat pain, mechanical (sharp) pain, and tactile threshold were obtained daily from untreated control skin and from capsaicin-treated skin during capsaicin application, and once weekly for 5 weeks following discontinuation of capsaicin. Heat pain sensation was assessed using a large (30 × 30 mm) and small (3 × 3 mm) thermode and different algorithms to assess pain threshold and suprathreshold heat pain. Skin biopsies were obtained and were processed for immunohistochemical localization of (ENFs) using the pan neuronal marker protein gene product 9.5. Capsaicin produced a rapid decrease in the number of ENFs, with nearly complete disappearance after 3 days of treatment. Heat pain evoked by the small, but not the large, thermode decreased dramatically after capsaicin treatment. The sensation of heat pain returned toward normal after 2-3 weeks following discontinuation of capsaicin treatment concordant with gradual reinnervation of the epidermis. Regression analysis indicated that the sensation of heat pain evoked by the small thermode correlated much better with the number of ENFs than heat pain evoked by the large thermode. The detection of sharp pain decreased moderately after capsaicin treatment. Assessment of heat pain sensation using small thermodes has potential for detecting sensory deficits in early stages of small fiber neuropathy.

Original languageEnglish (US)
Pages (from-to)241-250
Number of pages10
Issue number3
StatePublished - 2001

Bibliographical note

Funding Information:
This work was supported by NIH grants NS31223 (D.A.S.) and NS31397 (W.R.K.), and by Toray Industries, Tokyo (W.R.K.).


  • Capsaicin
  • Nerve degeneration
  • Neuropathy
  • Protein gene product 9.5
  • Skin


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