Botulinum toxin A injections combat neuropathic pain

By Eleanor McDermid

Botulinum toxin A injections have a sustained beneficial effect in patients with neuropathic pain, shows a randomised trial.

The patients received two treatments, each consisting of several subcutaneous injections, given 12 weeks apart. The number of botulinum toxin A injections per treatment was determined by the size of the affected area but did not exceed 60 sites, for a maximum of 300 units of botulinum toxin A.

In a linked commentary, Ralf Baron and Andreas Binder, from Christian-Albrechts-Universität Kiel in Germany, note that the patients required a local anaesthetic plus nitrous oxide to combat the pain of treatment. And despite this, more than half found the injections painful and a third reported severe pain.

"Thus, new delivery techniques for the toxin are needed before this method can be widely used in the clinic", they write in The Lancet Neurology.

The 34 patients in the botulinum toxin A group had an average pain score of 6.5 at baseline, and this fell to 4.6 after 24 weeks (ie, 12 weeks after the second injection), with responses ranging from a 1.9-point deterioration to an 8.8-point improvement.

The improvement in pain score was significantly greater than that reported by the 32 patients given placebo injections, whose average score reduced only slightly, from 6.4 to 5.8, report Nadine Attal (INSERM U-987, Boulogne-Billancourt, France) and study co-authors. They found a significant effect from the first week after the initial treatment, which increased after the second treatment.

In the botulinum toxin A group, 29% had at least a 50% reduction in pain intensity and 65% had at least a 30% reduction, versus a corresponding 16% and 25% of the placebo group. The number needed to treat to achieve one response of at least 50% was 7.3, which the researchers say compares favourably to currently recommended drugs, partly owing to the lack of systemic side effects, "although the application procedure is long and complex."

On the other hand, the team says that botulinum toxin A has little effect on symptoms such as sleep and anxiety, which systemic treatments such as pregabalin and duloxetine do address, leading them to suggest that botulinum toxin A should be considered mostly as an add-on treatment.

A response to botulinum toxin A was significantly more likely in patients with than without allodynia, and a greater intra-epidermal nerve fibre density also predicted response among the 29 patients who underwent a skin punch autopsy.

Similar features were previously reported in patients who responded to systemic oxcarbazepine treatment, note Baron and Binder in their commentary, "underpinning the notion that preservation of nociceptive fibres is a prerequisite for treatment response."

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