Canadian Research


Q&A with Dr. Gary J. Bennett, PhD
November 2, 2016

Professor Bennett is a research scientist with a long standing interest in CRPS. He was formerly Canada Senior Research Chair and Professor, Dept. Anesthesiology, McGill University and he is currently Adjunct Professor, Dept. Anesthesiology, University California San Diego. The reader should note that Prof. Bennett is not a medical doctor and thus cannot give medical advice.
Our call for questions elicited very many responses and I am unable to answer them all here. We hope to repeat this chat at a later date to answer more of your questions.

Q1: What is the most important thing(s) you could tell someone about CRPS research?
GJB: I realize how lonely the CRPS patient must feel to have such a terrible and puzzling condition. I hope it helps a little to know that there are hundreds of scientists and physicians doing research aimed at helping. In fact, we have recently formed an International Research Consortium in order to promote co-operation between research centers in North America, South America, Europe, Asia, and Australia. We believe that finding a cure for CRPS will be easier if we understand it better. In addition clinical research ("clinical trials") is necessary for us to test potential treatments.
Q2: Please explain the Budapest Criteria. Is there ongoing research on the Budapest criteria?
GJB: One of our problems is that CRPS has very diverse symptoms when one patient is compared to another, and even when a given patient is compared to herself over time. In the past, this led to arguments as to how to correctly diagnosis CRPS. A meeting of leading CRPS doctors was held in Budapest in 2003 to address this problem. As a result of this meeting and the research that it generated, we now have an internationally agreed-upon set of rules for diagnosing CRPS - these rules are called the "Budapest criteria".
Q3: What is the significance of HLA-DR1 in CRPS?
GJB: Human leucocyte antigen (HLA) DR1 is a gene on chromosome 6 that encodes for a protein that appears on leucocytes (white blood cells). It is one of several related genes that allow the immune system to tell the difference between self and non-self. Small mutations in this gene occur very commonly and there is a hypothesis that they cause auto-immune diseases (diseases where the immune system attacks the body rather than pathogens). There have been a couple of reports suggesting that inherited variation in this gene might be associated with CRPS - either as a cause or perhaps a contributory factor. Research on this question is continuing. No clear answer is yet available.
Q4: Are CRPS I and II the same disease? What is CRPS-NOS?
GJB: Complex Regional Pain Syndrome (CRPS) type I was formerly known as Reflex Sympathetic Dystrophy (RSD), while CRPS type II was formerly known as causalgia. For type II there is conclusive evidence of nerve injury as a precipitating event, while conclusive evidence is lacking for type I. However, in all other respects types I and II appear to be the same and many, but not all, doctors and researchers believe that they are essentially the same disease, the difference being that in type I the nerve injury is difficult to demonstrate because it is partial or involves a small nerve.

I am not certain, but "CRPS-NOS" probably means "CRPS- not otherwise specified", that is, a case of CRPS where there is no evidence about whether there might be a nerve injury.
Q5: I had heard of IVIG treatment. What is it and will it help patients?
GJB: Intravenous immunoglobulin (IVIG) infusions are used to treat certain autoimmune diseases. Immunoglobulins are antibody molecules. Thus if a physician thought that CRPS was due to an autoimmune reaction, then he might consider a trial with IVIG. A single dose of IVIG is made by pooling the immunoglobulins found in blood donations from several hundreds of donors. Thus it is in short supply and quite expensive. Moreover, there is the potential of danger due to exposure to material from so many donors (for example, one might have had an undetected viral infection). To the best of my knowledge there is no solid evidence that IVIG treatment helps CRPS patients.
Q6: Is ketamine treatment a viable option for CRPS? Are there any safety concerns with ketamine? Is there a ketamine protocol? If so, can Canadian doctors use it?
GJB: There is evidence that repeated IV infusions of ketamine bring at least temporary relief for many CRPS patients. It is reported that the pain relief lasts for months and can be re-instated by another series of ketamine infusions. The evidence indicates that this is a safe procedure. Ketamine infusions are also being investigated as a treatment for chronic depression.

There is no universally agreed upon protocol for CRPS treatment as to how many days of infusion are necessary or as to what is the best dose. The Reflex Sympathetic Dystrophy Syndrome Association (RSDSA; is in the process of organizing physicians who use this treatment in an effort to establish and standardize the best treatment protocol. I am not aware of whether or not this treatment is being used for CRPS patients in Canada.
Q7: What were some of the theories on the cause of CRPS?
GJB: There is no generally accepted theory as to the cause of CRPS. However, most theories involve the idea of an abnormal inflammatory response that is somehow affecting the nervous system.

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