01/2014 News: Researchers Close in on Causes of CRPS
Pain Medicine
by David Wild anesthesiologynews.com cluster excerpt: (w/ breakdown) :p which are you? I've added some links to help decode what they are saying to us. I did NOT spend a ton of time on link research, just quick definitions for the reader in case it was needed. 1. One way of grouping CRPS patients is by looking at their distinct somatosensory dysfunctions, Dr. Baron said. Individuals with deficits in temperature detection but no allodynia, and with loss of small nerve fibers, innervation and nerve degeneration, can be classified as having a neuropathic disorder. 2. A second cluster of patients can be seen as having central sensitization, with normal temperature sensitivity but severe mechanical and thermal hyperalgesia. 3. A third patient cluster may have inflammatory CRPS, with deep hyperalgesia and heat hyperalgesia but no hyperalgesia to prick testing, Dr. Baron explained. There is MUCH, MUCH more in this research article. Like this excerpt: Not a Perfect Fit Ralf Baron, MD, vice chair of the Department of Neurology and head of the Division of Neurological Pain Research and Therapy at the University Hospital Schleswig-Holstein in Kiel, Germany, told attendees that until recently, CRPS was understood to be clearly a neuropathic pain disorder. However, CRPS does not fit with the 2008 redefinition of neuropathic pain, defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system” (Neurology 2008;70:1630-1635). “CRPS is neuropathic in that there are characteristic neuropathic sensory abnormalities, but it also shows signs of central sensitization, inflammation, and autonomic and motor abnormalities,” Dr. Baron said. Other topics: An Autoimmune Disease? An ‘Ultralocal’ Inflammatory Response? If I am duplicating a previous post, please forgive me, but I don't remember seeing this... buy ya know... that's not my strong suit anymore. I have a good memory but it is SHORT! ha! :rolleyes: Now if I can figure this poll thing out again.. |
Hmmm,
I will be interested in further results... |
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This is really great information. After years of wondering by my doctors and tons of testing, I am testing positive for autoimmune diseases... inflammatory in nature. This causes new pain... CRPS is really something. |
This 2008 article is quite old now because the TREND consortium has done further, more recent research work looking at both the possibilities of distinct phenotypes in CRPS and potential causes.
For anyone who doesn't know, TREND is the Dutch consortium headed by a Professor of Neurology in the Netherlands which was set up and funded by their government cash revenues from oil and gas taxation to perform an 8 year programme of comprehensive research into a wide range of aspects of the underlying pathology and the treatment of CRPS. The research is multi- centre and many of the papers were carried out with international partners in other institutions and organisations. The final research papers will all have been published now or will be finalised very soon since the 8 year research period ended in the last couple of years. TREND is the single most comprehensive, high quality programme of research that has been done anywhere in the world into CRPS and the professor who is the scientific director of TREND is one of, if not the, leading global expert on CRPS. He still treats patients in clinic as well as being actively involved in CRPS research and has been for most of his career so he sees both the research side and the real day to day needs and issues of his patients. Their research is also carried out to very high standards. Not all research is created equal - there is a lot of so called 'research', clinical case studies, papers and advice out there that isn't what you think it is - it has massively flawed methodology, tiny sample size, is poorly carried out, isn't referenced or the conclusions are unsupportable and so on - much of it isn't peer reviewed before publication either and that isn't always obvious. I recommend checking out the TREND website (published in Dutch and English). Many of the papers themselves are not published in full free of charge on there but it is a great start point. |
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I totally agree with you that what TREND is/was doing is a great thing! However, I can only find webcashed pages of their site http://webcache.googleusercontent.co...h/publications Do you have agood website for them? Perhaps all the research is concluded and therefore they are no longer hosting the site. |
Sorry, I should have been clearer - the first link to the 2014 article took me to a members only login page so I wasn't able to look at that itself. I will try the further links you sent and see if I can see it now. I was only commenting on the other article quoted from 2008 which was given as a supporting reference in the 2014 article.
They may have cached the site since the project has technically ceased. For anyone less familiar than Vrae with TREND, Search for research by Professor J.J. Van Hilten or Jacobus Van Hilten as he is an author on all of the TREND research papers. You may be able to access some of the papers from the UNiversity of Leiden website since he works there as an academic and clinician. I think Kev has quite a strong view on the skills or otherwise of the researcher at the Walton Centre in Liverpool who is referred to in the IVIG trials papers. The larger trial that researcher was involved in which is referred to in the 2014 paper (which included only 11 CRPS patients) isn't clear about recruitment criteria, methodology, exclusions etc so it is very difficult to assess the quality, reliability and consistency of his research and conclusions. His previous trial had only 12/13 CRPS patients but he clearly acknowledged the various trial limitations. The NHS in the UK is going to run a large, multi centre clinical trial looking at IVIG in CRPS -it may already be recruiting but I've not looked for a while. There seems to be a 'current view' that it may have a role in treating acute CRPS but perhaps is of limited or insufficient value in chronic cases of CRPS where patients have had it for more than a matter of months. It will be interesting to see the eventual outcome. I think but can't remember for sure that large NHS trial is recruiting people with acute, relatively recent onset CRPS and chronic patients are excluded. I'm pretty sure when I looked I wasn't eligible due to my disease duration. |
Well hell, you're absolutely right on both counts! :eek: So sorry folks. I should just delete this thread (not sure how to do that...crap). :o I didn't realize the supporting info was so old.. yikes!
and the link in this post is so weird!! If I try the link I have the same problem. If I google search CRPS then click news it's the first link and it lets me in to see the issue. Strange! Anywho.. I thought since I was able to get in I would copy and paste here. Thanks for the good catch Neurochic, and again, so sorry guys! ISSUE: JANUARY 2014 | VOLUME: 40:1 Researchers Close in on Causes of CRPS by David Wild Toronto—Researchers tasked with developing a rudimentary understanding of complex regional pain syndrome (CRPS) are dividing their attention in several different directions. According to experts who spoke at the 2013 International Congress on Neuropathic Pain, there is evidence for inflammatory, neuropathic and immunologic roots to the enigmatic syndrome, and further investigation into these three aspects of the condition is necessary for the development of more effective treatments. “These different contributing factors all influence each other, so we need to address all of them so that patients don’t get onto a downward spiral where each factor worsens another,” Anne Louise Oaklander, MD, PhD, associate neurologist at Massachusetts General Hospital and associate professor at Harvard Medical School, both in Boston, said in an interview after the panel discussion. Not a Perfect Fit Ralf Baron, MD, vice chair of the Department of Neurology and head of the Division of Neurological Pain Research and Therapy at the University Hospital Schleswig-Holstein in Kiel, Germany, told attendees that until recently, CRPS was understood to be clearly a neuropathic pain disorder. However, CRPS does not fit with the 2008 redefinition of neuropathic pain, defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system” (Neurology 2008;70:1630-1635). “CRPS is neuropathic in that there are characteristic neuropathic sensory abnormalities, but it also shows signs of central sensitization, inflammation, and autonomic and motor abnormalities,” Dr. Baron said. One way of grouping CRPS patients is by looking at their distinct somatosensory dysfunctions, Dr. Baron said. Individuals with deficits in temperature detection but no allodynia, and with loss of small nerve fibers, innervation and nerve degeneration, can be classified as having a neuropathic disorder. A second cluster of patients can be seen as having central sensitization, with normal temperature sensitivity but severe mechanical and thermal hyperalgesia. A third patient cluster may have inflammatory CRPS, with deep hyperalgesia and heat hyperalgesia but no hyperalgesia to prick testing, Dr. Baron explained. An Autoimmune Disease? Another way of understanding CRPS, proposed by Andreas Goebel, MD, PhD, senior lecturer and honorary consultant at the University of Liverpool and Walton Centre National Health Service Foundation Trust in Liverpool, United Kingdom, is that a subset of CRPS patients have an autoimmune disorder–related condition. “It is possible that a regional immune response is triggered following stress, inflammation and trauma,” he said. Dr. Goebel said some of the 15% of CRPS patients with refractory symptoms lasting longer than six to 12 months may fall into this group (Pain 2009;142:218-224). He noted that several studies support the autoimmune paradigm, with results showing that a subset of CRPS patients have elevated levels of serum antibodies to several bacterial pathogens. “Furthermore, there is evidence for CRPS serum immunoglobulin binding to peripheral nerves,” he said (Neurology 2004;9:1734-1736). Indeed, several small case series, including his own, have demonstrated the efficacy of intravenous immunoglobulin G (IgG) in subsets of patients with long-standing, refractory CRPS, Dr. Goebel said (Pain Med 2002;3:119-127). A randomized controlled trial of 12 patients with long-standing CRPS who received the agent found that 25% reported pain relief of at least 50% relative to baseline and 17% had improvements in pain of between 30% and 50% (Ann Intern Med 2010;152:152-158). Although IgG has anti-inflammatory effects in addition to being an immunomodulator, Dr. Goebel said IgG’s efficacy is likely not explained by its anti-inflammatory effect. “All of the investigations which we have done, both in the lab and clinically, have been leaning more and more toward confirming there is an autoimmune aspect to CRPS,” Dr. Goebel concluded. “However, since we do not know which structures the autoimmune response is targeting, our current evidence remains somewhat indirect.” According to Dr. Goebel, if some patients in fact have CRPS of autoimmune origin, “a range of potential therapies, such as therapeutic plasma exchange and B-cell modulating therapies, can be at our disposal. These have all been tried and tested in other autoimmune disorders, and we can have access to an armamentarium that we did not have before,” he said. An ‘Ultralocal’ Inflammatory Response? Frank Huygen, MD, PhD, professor of anesthesiology at Erasmus Medical Center in Rotterdam, the Netherlands, argued the inflammatory component of CRPS could be the most clinically meaningful element of the syndrome in some patients. However, rather than looking for systemic inflammation, he believes researchers need to consider an “ultralocal” inflammatory response. “There are inflammatory mediators that are increased in the blister fluid of an involved extremity in CRPS,” Dr. Huygen said. His own research has documented increased levels of interleukin-6 and tumor necrosis factor (TNF)–a in some patients (Eur J Pain 2008;12:716-721). In a small, placebo-controlled, randomized trial, Dr. Huygen and his colleagues showed that the anti-TNF drug infliximab (Remicade, Janssen) exacerbated symptoms in some CRPS patients, leading to discontinuation of the trial (Pain Pract 2013; May 22: doi: 10.1111/papr.12078). The researcher still believes there could be a role for infliximab and other biologics in the treatment of CRPS. “Although the sponsor stopped the study early, preliminary data showed enormous reductions in TNF–a levels in blister fluid with infliximab treatment, but these did not correlate with clinical changes,” he said. Summarizing the challenge of understanding and treating a complex syndrome, Dr. Baron suggested CRPS should no longer be seen monolithically as a neuropathic disorder. “As long as we do not have a clearer pathophysiological picture of CRPS patients, and because of the obvious heterogeneity of the signs, symptoms and mechanisms of the syndrome,” he said, “it would be wise to look at the condition separately from other classical neuropathic pain syndromes.” |
Lol Vrae :winky:
My pain doc got me onto the Liverpool IVig trial.... I'm due to start some time in the next few months. Dr Andreas Goebels in Liverpool has had my records, and knows I've had it for nearly 3 years.... I have mixed views on it obviously, but I kind of think I should try. My pain doc thinks the risks are pretty low (yes yes I know...:rolleyes:) and that I should go for it. Bram. |
Thanks Bram.. and we've got to try.. right? Life is full of all kinds of risks. It's part of living. I hope you'll keep us posted as you go. I am VERY interetsed in what you'll be doing. I would also like to try IVIG. I go for a block this morning. First one ever. honestly, not being pessimistic but I feel like.. okay, I'll do it. and I might even get beneit for a while (much like some meds I take), but I am highly doubtful this will be the end all be all of my situation. My pain has gotten very debilitating. I do believe we must start somewhere in trying to get a handle on it though.
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Bram im so glad you were able to get into the IVIG trial! It is something im wanting to try when I go to PA this summer.
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