Intradermal capsaicin as a neuropathic pain model in patients with unilateral sciatica.

AIM: This study compared the responses between patients with unilateral sciatica and pain-free volunteers following administration of intradermal capsaicin. METHODS Fourteen patients with unilateral sciatica and 12 pain-free volunteers received one injection per hour over 4 h of 1 µg and 10 µg capsaicin, into each calf. For each dose, spontaneous pain (10 cm VAS), area of flare (cm²) and the sum of allodynia and hyperalgesia radii across eight axes (cm) were recorded pre-injection and at 5, 15, 30, 45 and 60 min post injection. RESULTS: Sciatica subjects experienced higher spontaneous pain and hyperalgesia responses in both legs compared with pain-free volunteers. The largest mean difference in spontaneous pain was 2.8 cm (95% CI 1.6, 3.9) at 5 min in the unaffected leg following 10 µg. The largest mean difference in hyperalgesia was 19.7 cm (95% CI 12.4, 27.0) at 60 min in the unaffected leg following 10 µg. Allodynia was greater in patients than in controls with the largest mean difference of 2.9 cm (95% CI 1, 4.8) at 5 min following 10 µg in the affected leg. Allodynia was also higher in the affected leg compared with the unaffected leg in sciatica patients with the highest mean difference of 3.0 cm (95% CI 1.2, 4.7) at 5 min following 10 µg. CONCLUSIONS: The responses to intradermal capsaicin are quantitatively and qualitatively different in unilateral sciatica patients compared with pain-free controls.

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

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 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. CONCLUSION: 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.