A comparison of two formulations of intradermal capsaicin as models of neuropathic pain in healthy volunteers.
OBJECTIVE
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 microg in 10 ml 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 microg, but in all parameters the response was less at 100 microg with the Tween formulation.Mean area for hyperalgesia was 9 cm(2) [95% confidence interval (CI) 5, 13] higher with the HP-beta-CD formulation. Flare area was 5 cm(2) (95% CI 8, 13) greater with the HP-beta-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-microg dose of the Tween formulation contained only 39% of label strength in the aqueous phase, which may explain the lower pharmacodynamic response.


CONCLUSIONS
The formulations are comparable over the dose range 1-30 microg. The significantly lower pain response at the 100 microg dose in the Tween compared with the HP-beta-CD formulation is likely to be due to limitations in solubility at the 100 microg level. Given the greater ease of formulation and the superior dose-response relationship, the HP-beta-CD formulation is preferable for use in the model in future studies.
Pharmacy School, University of Gothenburg, Gothenburg, Sweden.
Helena
H
Gustafsson
Johanna
J
Akesson
Chai Li
CL
Lau
Desmond
D
Williams
Lisa
L
Miller
Sharon
S
Yap
Paul
P
Rolan
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000328:Adult; D002211:Capsaicin / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005079:Excipients; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced*; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced*; D018689:Sensory System Agents / Q000008:administration & dosage; D012737:Sex Factors; D016037:Single-Blind Method; D012867:Skin / Q000187:drug effects*; D013997:Time Factors; D055815:Young Adult; D047392:beta-Cyclodextrins / Q000008:administration & dosage*
D005079:Excipients; D018689:Sensory System Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002211:Capsaicin