A randomized, double-blind, placebo-controlled trial of injected capsaicin for pain in Morton's neuroma.

Intermetatarsal neuroma or Morton's neuroma is a painful condition of the foot resulting from an entrapment of the common digital nerve typically in the third intermetatarsal space. The pain can be severe and especially problematic with walking. Treatment options are limited and surgery may lead to permanent numbness in the toes. Capsaicin, the pungent ingredient of hot peppers, produces analgesia by inducing retraction of nociceptive afferents from the area of innervation and is effective in treating certain neuropathic pain disorders. A randomized double-blind placebo-controlled study was conducted to test the efficacy, tolerability, and safety of a single 0.1 mg dose of capsaicin vs placebo injected into the region of the neuroma. A total of 58 subjects diagnosed with Morton's neuroma with foot pain ≥4 (0-10 numerical pain rating scale) were injected with 2 mL of lidocaine into the intermetatarsal space proximal to the neuroma to provide local anesthesia. After 5 minutes, 0.1 mg capsaicin or placebo was injected into the intermetatarsal space containing the painful neuroma. Average foot pain was rated for 2 weeks before through 4 weeks after injection. At weeks 1 and 4, the decrease in pain was significantly greater in the subjects treated with capsaicin (P = 0.021 and P = 0.019, respectively). A trend toward significance was noted at weeks 2 and 3. Improvements in functional interference scores and reductions in oral analgesic use were also seen in the capsaicin-treated group. These findings suggest that injection of capsaicin is an efficacious treatment option for patients with painful intermetatarsal neuroma.

Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy.

A length-dependent neuropathy with pain in the feet is a common complication of diabetes (painful diabetic neuropathy). It was hypothesized that pain may arise from sensitized-hyperactive cutaneous nociceptors, and that this abnormal signaling may be reduced by topical administration of the α(2)-adrenergic agonist, clonidine, to the painful area. This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Nociceptor function was measured by determining the painfulness of 0.1% topical capsaicin applied to the pretibial area of each subject for 30minutes during screening. Subjects were then randomized to receive 0.1% topical clonidine gel (n=89) or placebo gel (n=90) applied 3 times a day to their feet for 12weeks. The difference in foot pain at week 12 in relation to baseline, rated on a 0-10 numerical pain rating scale (NPRS), was compared between groups. Baseline NPRS was imputed for missing data for subjects who terminated the study early. The subjects treated with clonidine showed a trend toward decreased foot pain compared to the placebo-treated group (the primary endpoint; P=0.07). In subjects who felt any level of pain to capsaicin, clonidine was superior to placebo (P<0.05). In subjects with a capsaicin pain rating ⩾2 (0-10, NPRS), the mean decrease in foot pain was 2.6 for active compared to 1.4 for placebo (P=0.01). Topical clonidine gel significantly reduces the level of foot pain in painful diabetic neuropathy subjects with functional (and possibly sensitized) nociceptors in the affected skin as revealed by testing with topical capsaicin. Screening for cutaneous nociceptor function may help distinguish candidates for topical therapy for neuropathic pain.