Clinical Trial Finds Botulinum Toxin Can Soothe Neuropathic Pain

Botulinum toxin for neuropathic pain

Image: 3-D model of botulinum toxin protein. Credit: Wikimedia Commons.

Botulinum toxin (its commercial form is made by the pharmaceutical company Allergan and marketed as Botox) is popularly known for its ability to iron out wrinkles. But since the late 1980s, researchers have appreciated that the drug, which uses a toxin made by bacteria, can relieve chronic pain. More recently, several studies have found that botulinum toxin can reduce pain arising from nerve damage—so-called neuropathic pain. However, those studies have been too small to draw strong conclusions.

But now, a larger clinical trial published February 29 in the journal The Lancet Neurology finds that repeated injections of the toxin under the skin of the painful area can be an effective and safe way to help soothe neuropathic pain.

“This trial is important as we desperately need new options for treating neuropathic pain and regional treatment can avoid systemic side effects,” writes David Bennett in an email to RELIEF; systemic side effects are those that occur throughout the body. Bennett is a pain researcher at the University of Oxford, UK, who has examined how the toxin may relieve pain, but was not involved in the current study.

Does it work?
For the new trial, conducted in two outpatient clinics in France and one in Brazil, 66 patients with neuropathic pain rated the intensity of their pain at baseline on a scale from 0 to 10. Then, half received a version of the toxin called BoNT-A, and the rest received a placebo. A second dose of BoNT-A or placebo was given 12 weeks later. Each week after treatment, patients again rated their pain intensity.

The experiment was a “double blind” study in which neither the researchers nor the patients knew who received the toxin and who did not. This approach, considered the highest standard in clinical trials, is followed in order to prevent the expectations or preferences of the experimenters or the patients from affecting the results.

Following treatment, patients administered BoNT-A consistently rated their pain as less intense than they did before treatment. This was not the case for those given a placebo, suggesting that the toxin did indeed relieve pain. Moreover, the second dose did not just extend the pain relief for those that responded to BoNT-A, but also added to it, since about a quarter of patients not helped by the first dose reported pain relief after the second.

Do some benefit more than others?
Neuropathic pain can manifest differently from patient to patient, and so the researchers next asked if certain patients responded better to BoNT-A than others. They found that those who responded best to treatment were patients who felt pain from light touch, and who were more sensitive to hot and cold temperatures, before treatment began.

“This shows that there is a subgroup of patients who are very prone to respond to the toxin, and a subgroup who are not,” says Nadine Attal, who led the trial. Attal is a neurologist and pain researcher at the French Institute of Health and Medical Research, Boulogne-Billancourt, France.

With these benefits came only one clear side effect: pain from the injection itself. Bennett and other researchers say that for BoNT-A to be widely adopted as a treatment, researchers need to find a way to administer it differently. Attal agrees, saying that ideally BoNT-A would not be given under the skin.

The trial stands in contrast to an even larger but unpublished trial from Allergan, which failed to detect any effect of the toxin on neuropathic pain. While it is not clear why that study failed to meet its goal, Attal thinks the answer may relate to the kind of neuropathic pain for which the drug was tested, namely post-herpetic neuralgia (PHN); PHN is pain from nerve injury that is observed in some patients who have shingles. Because pain from PHN can resolve on its own, Attal suspects that patients who received the placebo in the Allergan study may have recovered over time without the drug, making it harder to detect effects of the toxin.

Nonetheless, for Attal, the results from the current study are convincing enough for her to use the toxin off-label to treat her patients with neuropathic pain; currently, migraine is the only chronic pain condition approved for BoNT-A treatment. With a better means of delivering the drug, perhaps BoNT-A will one day gain approval for neuropathic pain treatment too. —Matthew Soleiman

To read about the research in more detail, see the related Pain Research Forum news story here.

Matthew Soleiman is a neuroscientist-turned-science writer currently residing in Nashville, Tennessee. Follow him on Twitter @MatthewSoleiman.