Capsaicin or Menthol Sensitization Induces Quantitative But No Qualitative Changes to Thermal and Mechanical Pain Thresholds

Abstract

To analyze whether sensitization procedures employed in experimental human pain models introduce additional components to pain measurements resulting in a different kind of pain or whether they are limited to quantitative changes resulting in the same pain at higher intensity. Heat, mechanical (von Frey hairs), and cold stimuli were applied to 69 men and 56 women, aged 18 to 46 years, prior and subsequently to sensitization by dermal capsaicin or menthol application. Sensitization decreased the fraction of censored data, that is, thresholds at the technical limit of 52.5 degrees C or 0 degrees C or 300 g von Frey hairs, from 38 to 21 patients with von Frey hairs, from 30 to 19 patients with cold stimuli (chi(2) tests: P<0.001), whereas pain thresholds to heat never reached its technical maximum. In the 75 patients without censored data, capsaicin sensitization decreased the heat pain thresholds from 44.7+/-2.1 degrees C to 36.8+/-3.3 degrees C, the von Frey pain thresholds from 78.2+/-74 g to 33.9+/-37.8 g, and menthol sensitization decreased cold pain thresholds from 13+/-8.4 degrees C to 19.3+/-9.2 degrees C (paired comparisons: all P<0.001). However, for each stimulus, only 1 single principal component of the variance of nonsensitized and sensitized thresholds with an eigenvalue >1 was identified by principal component analysis, explaining 64.8%, 84.8%, and 94.4% of the total variance for heat, mechanical, and cold stimuli, respectively, and indicating that nonsensitized and sensitized pain thresholds shared the same main source of variance. The main effect of sensitization by capsaicin or menthol application is a quantitative decrease in thermal and mechanical pain threshold with the methodologic benefit of decreasing the incidence of censored data. A qualitative change in pain thresholds by sensitization is not supported by the present statistical analysis at level of primary hyperalgesia.