Hope on the Horizon

Written by Karen Brinkley, MD, Associate Professor of Medicine, University of Toronto

If you have CRPS, you may already realize that existing treatments do not work as well as we would like.  The best hope for improved treatments will come from a better understanding of what is going wrong in CRPS, so that we are better able to fix it.  In this column, new developments in our understanding about CRPS, and implications for treatment are reviewed.

Developments in the understanding and treatment of other autoimmune conditions, which may be relevant to CRPS, are also highlighted, in the hope of generating research interest to explore new treatment possibilities that are so desperately needed.

Topical ambroxol for CRPS

Researchers in Germany describe some success in a small case series of 8 CRPS patients treated with 20% ambroxol cream. Ambroxol is primarily used to enhance mucus clearance in patients with viral infections, such as the common cold. It likely has multiple modes of action, but because it blocks sodium channels on nerve cells, it can also reduce pain. In the report 6 of 8 patients had reduction of pain and edema, 6 of 8 had improved motor function, 4 of 8 had improvement in skin temperature and skin reddening. This report suggests that ambroxol cream may be a useful addition to CRPS treatments, but further studies will be needed.

Low dose interleukin 2 for autoimmune disorders

Interleukin 2 (IL-2) is a cytokine naturally produced by the body. It has many different roles in regulating the immune system. While important for the growth and proliferation of many types of lymphocytes (a type of white blood cell), its role in the development of regulatory T cells (Tregs) is increasingly recognized. Tregs are partly responsible for controlling inflammation and over-exuberant immune responses, as occurs in autoimmune disorders. Recent studies with several autoimmune disorders suggest that low dose IL-2 may increase the number of Tregs, and help dampen the autoimmune process. This may be very relevant to CRPS, as there is increasing evidence that CRPS is, at least in part, an autoimmune process. While not without risks, it might be reasonable to see if this type of treatment would be helpful in CRPS patients with evidence of autoimmunity, in whom other treatments have been ineffective.

Vagus nerve stimulation for autoimmune disorders

Vagus nerve stimulation is another treatment modality showing promise in treating autoimmune conditions. The nervous system is known to influence the immune system, at least in part through the action of the 2 branches of the autonomic nervous system (which controls unconscious bodily functions): the sympathetic and parasympathetic nervous systems.  In one circuit, termed “the inflammatory reflex,” action potentials transmitted via the vagus nerve (part of the parasympathetic nervous system) inhibit the production of tumor necrosis factor (TNF), an inflammatory molecule that may be increased in certain phases of CRPS. TNF is also increased in rheumatoid arthritis (RA), an autoimmune disorder with prominent joint involvement.  It has been shown in small studies that stimulating the vagus nerve reduces TNF and improves symptoms in RA. Might vagus nerve stimulation be helpful in CRPS? Further studies may be warranted, especially now that portable vagus nerve stimulators are available, and do not require surgical implantation.


  1. Successful treatment of complex regional pain syndrome with topical ambroxol: a case series. Maihöfner C, et al. Pain Manag. 2018.
  2. Targeting IL-2: an unexpected effect in treating immunological diseases. Congxiu Ye, et al. Signal Transduction and Targeted Therapy volume 3, Article number: 2 (2018)
  3. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Koopman  F, et al.
    Proc Natl Acad Sci U S A. 2016 Jul 19; 113(29): 8284–8289.
  4. Scientific American: Can Zapping the Vagus Nerve Jump-Start Immunity?

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