SLR - July 2016 - Chelsea Viola

A Randomized, Double-Blind, Placebo-Controlled Trial of Injected Capsaicin for Pain in Morton’s Neuroma

Reference:
Campbell CM, Diamond E, Schmidt WK, Kelly M, Allen R, Houghton W, Brady KL, Campbell JN. A Randomized, Double-Blind, Placebo-Controlled Trial of Injected Capsaicin for Pain in Morton’s Neuroma. Pain. 2016 Jun;157;6: 1297–1304.

Scientific Literature Review

Reviewed By: Chelsea Viola, DPM
Residency Program: Morristown Medical Center, Atlantic Health System, New Jersey

Podiatric Relevance: Morton’s neuroma is a common complaint in the outpatient podiatric surgical office. Proper treatment is difficult, with many options from which the podiatric physician and surgeon must choose. According to a Cochrane review, there is insufficient evidence to assess the comparative effectiveness of surgical and nonsurgical interventions for Morton’s neuroma. This leads to confusion on treatment protocol, varying conservative treatments and differing times to surgical intervention. Even after surgical intervention, many patients relate no decrease in pain or a change in symptoms to numbness in the distribution of the treated nerve. This study was performed in order to determine whether capsaicin injected into the neuroma could be an effective conservative treatment of the symptoms associated with Morton’s neuroma. Capsaicin is successfully used in treating certain neuropathic pain disorders by inducing retraction of nociceptive afferents from the area of innervation.

Methods: A randomized double-blind placebo-controlled study was conducted, which included a screening process prior to injection of the capsaicin. Subjects who were included in the study were required to have greater than or equal to four out of ten on the eleven-point numeric pain rating scale with zero being no pain at all and ten being the worst possible pain. Subjects included were also required to have had failure of conservative treatment, which could have included orthotics, arch supports or oral analgesics. Subjects who were excluded were those who had clinical evidence of some other cause of foot pain or allergies to either lidocaine or capsaicin. The subjects were then randomized. On injection day, the subjects received 2 percent lidocaine with epinephrine (2mL) into the third intermetatarsal space, just distal to the head of the metatarsal. In a randomized, double-blinded fashion, the subjects either received 0.1mg capsaicin (0.2mg/mL) or placebo (polyethylene glycol 300 [PEG]) in water at a 1:1 ratio. Pain was then rated immediately after injection and at 15, 30 and 45 minutes, and then again at one, two, three and four hours after study drug administration.

Results: The follow-up visit was then performed at four weeks after the injection, during which they performed a foot pain severity scoring test. All uses of analgesics, daily pain scores and brief pain inventory interference items (walking, sleeping, life enjoyment, mood, relationships, work and general activity) were recorded by the patients in their “diaries” prior to the four-week follow-up visit. Out of the 58 total subjects, 28 received the placebo and 30 received the capsaicin. The mean reduction in pain from baseline was larger in the capsaicin group than in the placebo. A significant reduction of pain was observed during week one post injection. Measures of mood and walking interference improved from baseline to week four in the capsaicin group. Improvement in measures of sleep and life enjoyment trended toward significance in the capsaicin group. The subjects who received capsaicin as opposed to placebo also required significantly less analgesics. A larger percentage of the subjects in the placebo group also reported more neuropathic pain at any time than subjects in the capsaicin group. Pain after injection, however, was greater in the group receiving capsaicin than the placebo with magnitude of pain varying with time. It is to be noted that change in pain at week four was not correlated with the magnitude of procedural pain.

Conclusions: The authors of this investigation have concluded that the patients treated with capsaicin experienced a significant reduction in pain compared with the placebo at four weeks post injection into Morton’s neuroma. This reduction was associated with the use of fewer pain medications, less functional interference in mood and walking, and trends suggesting less functional interference in sleep and life enjoyment as recorded by the patients. This could be a promising new conservative treatment of neuroma pain. High-dose capsaicin cream used topically to treat neuropathic pain is effective for about 12 weeks. The length of effectiveness of injectable capsaicin has yet to be determined and is in dire need of determination prior to any routine clinical administration of capsaicin. Also, the injectable dose was great than, but based on, the skin topical dose but at a lower percent concentration. The proper effective dose with the longest duration of effectiveness is yet to be determined.

Considering the amount of treatments available for Morton’s neuroma, and no gold standard, all patients have to be evaluated individually with possibly different treatments for each. The main concern noted in this study was that with surgical neurectomy, patients experience a loss of sensation in the distribution of the nerve. In many patients, however, this is the exact result they are hoping to achieve with surgical removal of the neuroma and branches. Therefore, a juxtaposition of the surgical procedure with capsaicin injection is difficult and is a comparison of two unequal treatments. A better comparison would be injectable capsaicin versus sclerosing agents, such as alcohol. The issue with sclerosing injections is not only that it could take three to five before the pain is resolved, but also pain on each injection is high and not tolerated well. With some subjects, sclerosing agents never remove the discomfort and surgical intervention is then indicated.

The result of this study is promising, and the more treatments available in the arsenal for neuroma pain will only help the patients. It could be that when sclerosing agents are not effective, capsaicin would be, or vice versa. Moving forward, the information that needs to be acquired is the effective dose of capsaicin, duration of effectiveness and comparison studies to commonly used sclerosing agents. It may become evident that capsaicin is superior; however, there is still the question of whether this pain relief is permanent, considering it was mentioned in this study that the maximum concentration of capsaicin was noted at one hour post injection. Capsaicin is metabolized quickly by cytochrome enzymes in the liver, and the maximum concentration time observed was similar to that observed with ingested and topically applied capsaicin. If this treatment becomes mainstream, further studies necessary would be time to surgical invention post capsaicin treatment.

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