Ambroxol for the treatment of fibromyalgia: science or fiction?

Abstract

Fibromyalgia appears to present in subgroups with regard to biological pain induction, with primarily inflammatory, neuropathic/neurodegenerative, sympathetic, oxidative, nitrosative, or muscular factors and/or central sensitization. Recent research has also discussed glial activation or interrupted dopaminergic neurotransmission, as well as increased skin mast cells and mitochondrial dysfunction. Therapy is difficult, and the treatment options used so far mostly just have the potential to address only one of these aspects. As ambroxol addresses all of them in a single substance and furthermore also reduces visceral hypersensitivity, in fibromyalgia existing as irritable bowel syndrome or chronic bladder pain, it should be systematically investigated for this purpose. Encouraged by first clinical observations of two working groups using topical or oral ambroxol for fibromyalgia treatments, the present paper outlines the scientific argument for this approach by looking at each of the aforementioned aspects of this complex disease and summarizes putative modes of action of ambroxol. Nevertheless, at this point the evidence basis for ambroxol is not strong enough for clinical recommendation.

Ambroxol for neuropathic pain: hiding in plain sight?

“…Regarding safety, the clinical data for ambroxol for the treatment of pain seem favourable. In the studies reviewed here, no adverse skin effects or reactions were reported for topical ambroxol, 45–47,58 whereas oral formulations have so far been associated with a low incidence of minor side effects, including nausea, constipation, bowel/abdominal discomfort, heartburn, and dizziness. 41,61 Regarding its use in approved indications (ie, secretolytic therapy, respiratory distress syndrome, and pain relief in sore throat), the European Medicines Agency (EMA) published a revised safety assessment in 2015 which stated that, based on a small number of case reports, there is weak evidence of a possible risk of hypersensitivity and skin reactions.…”

“…80 There is also increasing evidence for involvement of inflammatory factors, oxidative stress, and neurodegenerative changes. 45 The overlap between fibromyalgia-proposed pathophysiological components and multiple mechanisms of action of ambroxol has been thoroughly discussed by Kern and Schwickert. 45 In 2017, the results of an open-label pilot study of oral ambroxol treatment (30 mg 3 times a day for 1 month) as an add-on to stable pharmacological therapy were published.…”

“…45 The overlap between fibromyalgia-proposed pathophysiological components and multiple mechanisms of action of ambroxol has been thoroughly discussed by Kern and Schwickert. 45 In 2017, the results of an open-label pilot study of oral ambroxol treatment (30 mg 3 times a day for 1 month) as an add-on to stable pharmacological therapy were published. 61 Twenty-five female patients with severe fibromyalgia (according to the Revised Fibromyalgia Impact Questionnaire [FIQ-R]) completed the study.…”

Dual‐action ambroxol in treatment of chronic pain in Gaucher Disease

“…It might also be associated with the central sensitization phenomenon that amplifies neuronal activation in pain‐processing regions in patients with chronic pain, and can provoke long‐term changes in brain functioning (Woolf, ). Ambroxol potentially reversed central pain sensitization during initial treatment (Kern & Schwickert, ). This effect might be associated with Nav1.8 channels and/or the scavenging activity of free radicals (Jang, Song, Shin, Han, & Lee, ).…”

Topical Ambroxol 20% for the Treatment of Classical Trigeminal Neuralgia – A New Option? Initial Clinical Case Observations

“…The intrathecal administration also showed an anti‐allodynic effect . Reductions of allodynia and hyperalgesia by topical ambroxol in humans so far have been reported in case series for neuropathic pain, nociceptive pain, mixed pain situations, and even topical and oral, given for hypersensitivities in fibromyalgia . For the patients described in this article, however, an alleviation of allodynic symptoms thus could be explained.…”