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Unproven Intervention: Could OTC Topical Ambroxol Relieve CRPS Symptoms?

The cream may reduce pain and improve motor function in patients with complex regional pain syndrome

With Kai-Uwe Kern, MD, and Gary Jay, MD

Complex regional pain syndrome (CRPS) is a chronic condition that often affects one limb or extremity, following an injury or surgery to that part of the body. The causes and mechanisms behind CRPS remain poorly understood, while the syndrome typically presents with localized inflammation, edema, hyperhidrosis, and allodynia.1

“The most telling part of CRPS is allodynia,” said Gary Jay, MD, clinical professor of neurology within the Division of Headache and Pain at the University of North Carolina, Chapel Hill, and a member of PPM’s Editorial Advisory Board. “The classic sign is, if a patient holds out their arm and you just blow lightly on it, they’ll hit the roof.”

Common treatments for CRPS currently include physical therapy, psychotherapy, and medication. FDA has not approved any medication specifically indicated for the treatment of CRPS, and no combination of drugs has shown high levels of efficacy across patients with the condition.1

Ambroxol: A Mini European Case Series

Ambroxol is a mucolytic commonly used in Europe and other parts of the world to treat respiratory diseases like bronchitis. It is also used topically, as a lozenge, to treat sore throat and pharyngitis. Along with breaking down mucus and acting as a local anesthetic, evidence suggests that ambroxol may have anti-inflammatory properties.2

While it is available over the counter in Germany and other countries,3 FDA has not approved ambroxol in the US.4 The most common adverse event is a skin reaction, in some cases severe, according to an EMA review of the drug’s risks in 2015.5

Kai-Uwe Kern, MD, private docent at the Institute for Pain Medicine/Pain Practice in Wiesbaden, Germany, conducted a small case series over the course of four months in 2016. In a new report, his team has presented their clinical observations of how eight patients (seven females and one male, ages 27 to 72), who had been experiencing CRPS symptoms for under a year, responded to treatment with topical ambroxol 20% cream (50.0 g: ambroxol 10.0 g, DMSO cream 5.0 g, Linola cream ad 50.0 g).

Out of the eight patients, six reported a reduction in pain intensity on a numerical rating scale (NRS) from 0 to 10. Of the two remaining patients, one did not experience pain relief after about a week of ambroxol use and the other had only reported low levels of pain prior to ambroxol use. The most substantial results were a decrease in pain at rest from NRS 7 to NRS 0-1 for one patient and a decrease in pain during activity from NRS 6-8 to NRS 3 in another patient. Improvements in function were also reported in six patients, including the patient with low levels of initial pain. Of the two remaining patients, one did not report functional improvement after about a week of ambroxol use and the other had not reported functional impairment prior to ambroxol use. None of the patients reported any adverse effects, with duration of ambroxol use ranging from two days to seven months and with twice daily application being typical for sustained pain relief.6

Previously, Dr. Kern published a similar case series outlining the generally positive response to topical ambroxol treatment experienced by seven patients with neuropathic pain.8 Prior research on ambroxol’s pain reduction properties has largely been based on animal studies which have indicated that the drug blocks sodium channels Nav1.7 and Nav1.8,6 the two channels associated most directly with neuropathic pain according to Dr. Jay.

The cream may reduce pain and improve motor function in patients with CRPS. (Source: 123RF)

Practical Application

Dr. Jay said he would not have a problem suggesting ambroxol off-label to a patient with CRPS. “What it boils down to, as a clinician, is would a drug hurt somebody if you were to try it? And the answer is no, particularly because it’s percutaneous,” he said. “But, would I guarantee it’s going to help? Absolutely not, because there’s not enough evidence in this report.”

One further critique of Dr. Kern’s CRPS case series is that some of the observed benefits may be attributed to DMSO (dimethylsulfoxide) cream, which is believed to have some pain-relieving features itself, according to Dr. Jay. To address this possibility, in the two and a half years since concluding the case series, Dr. Kern has treated all of his CRPS patients with ambroxol alone. He claims that the observed benefits persist without DMSO.

Additionally, while none of the eight patients in the case series had been experiencing symptoms of CRPS for over a year, Dr. Kern said he has since treated others who have suffered from the syndrome for up to two years. These patients found similar relief with topical ambroxol.

Widely available outside of the US, ambroxol shows some practical promise. It also seems highly tolerable, as Dr. Kern noted having never observed any severe skin reactions and only a few cases of redness or mild eczema in patients who had been using ambroxol for extended periods.

“It’s very easy to use,” he said, noting that with CRPS, “function is so impaired that you are happy for any improvement.”

Call for Research

Dr. Kern recognizes that, while physicians from around the world have since connected with him to share their accounts of ambroxol’s efficacy in treating CRPS and neuropathic pain, the body of evidence remains largely anecdotal. He welcomes a large, formalized study of ambroxol’s efficacy. “I think it’s a real option. We have to discuss, publish, and collect the facts and feedback,” said Dr. Kern. “I look at it very critically, because I brought this idea to the world. So, I have to be critical of what could be on the other side of the idea.”

Last updated on: April 2, 2019
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