A comparison of two formulations of intradermal capsaicin as models of neuropathic pain in healthy volunteers

Abstract

AIMS: To compare the dose–response relationships of two formulations [Tween- or hydroxypropyl-b cyclodextrin (HP-b-CD)-based] of intradermal capsaicin in healthy volunteers and to assess the effect of potential covariates of response. One, 10, 30 and 100 mg in 10ml were compared for the outcomes of flare, spontaneous pain, mechanical allodynia and hyperalgesia in eight healthy men and eight healthy women. RESULTS: The formulations produced comparable responses at doses 1, 10 and 30 mg, but in all parameters the response was less at 100 mg with the Tween formulation.Mean area for hyperalgesia was 9 cm2 [95% confidence interval (CI) 5, 13] higher with the HP-b-CD formulation. Flare area was 5 cm2 (95% CI 8, 13) greater with the HP-b-CD formulation. There was a significant difference between pain responses from the injection site on the upper forearm compared with the lower forearm on all four pain assessments. In contrast, significant differences were seen in pain response between nondominant and dominant arm for flare, allodynia and hyperalgesia but not for spontaneous pain. A significant difference in sex was seen only for hyperalgesia. The nominal 100-mg dose of the Tween formulation contained only 39% of label strength in the aqueous phase, which may explain the lower pharmacodynamic response. CONCLUSION: The formulations are comparable over the dose range 1–30 mg. The significantly lower pain response at the 100 mg dose in the Tween compared with the HP-b-CD formulation is likely to be due to limitations in solubility at the 100 mg level. Given the greater ease of formulation and the superior dose–response relationship, the HP-b-CD formulation is preferable for use in the model in future studies.