Hi,
This is the article I have been on about for awhile. It is finally avilable for you to read.
http://appneurology.com/showArticle....leId=196513289
Hugs, Roz

thanks Roz for posting this I have saved it and am reading it now

Hi Roz,

This is the single best overview, general article on RSD/CRPS I have ever read!!

I've only just seen this post - the internet cable damage caused by the earthquake will take weeks to fix, so my connections are very dodgy - but I'm so glad I saw this. The medications section is especially interesting.

Roz, how are you? Noticed your name not cropping up so often, hope you are all right, many thanks for posting this,
all the best

Hi, If you read the first article it talks about sodium channels.

According to Cruciani, constant pain signals from the periphery may lead to changes in the posterior horn of the spinal cord, such as an increase in the number of N-methyl-d-aspartic acid (NMDA) receptors that bind glutamate, an increase in the number of certain types of sodium channels, or a change in the expression of the calcitonin gene-related peptide. An increase in proinflammatory cytokines also has been identified



Sodium Channels as Molecular Targets in Pain Research

Given what we have learned about sodium channels, where do we go next in the search for better treatments for pain syndromes? The answer to this question is not entirely clear at this time. We can, however, come to a number of conclusions. First, sodium channels are important participants in electrogenesis within primary sensory neurons, including DRG neurons. Second, a multiplicity of sodium channels are present within DRG neurons, where they probably subserve multiple functions (transduction, signal amplification, action potential electrogenesis, etc.) and interact in a complex manner. Third, DRG neurons express a number of sodium channel genes (SNS/PN3, NaN, PN1, and NaG) in a preferential manner, at levels much higher than in any other neuronal cell type. This observation may present a therapeutic opportunity for the selective manipulation of primary sensory neurons in general, or nociceptive neurons in particular. Fourth, sodium channel expression in DRG neurons is highly dynamic, with multiple sodium channel genes (including -III, SNS/PN3, and NaN) exhibiting up- or down-regulation after various injuries to these cells. Importantly, different injuries may trigger opposing changes of certain sodium channel genes (e.g., down-regulation of SNS/PN3 after axotomy vs. up-regulation in the carageenan inflammation model) in DRG neurons, so that it may be difficult to extrapolate from one model system to another. Nevertheless, we have learned, at a minimum, that sodium channel expression in DRG neurons is dynamic and can change significantly after injury, and that changes in sodium channel expression can substantially alter excitability in these cells.

Delineation of the precise role(s) of each sodium channel subtype in the physiology of DRG neurons and the pathophysiology of pain remains to be established, and the utility of selective blockade of each channel subtype as an approach to the treatment of pain will require further careful study. However, the stage has been set for these investigations. It is quite likely, in our opinion, that sodium channel blockade will emerge as a viable strategy for pharmacologic treatment of pain.

http://www.pnas.org/cgi/content/full/96/14/7635

Our studies demonstrate that multiple sodium channels, with distinct electrophysiological properties, are encoded by distinct mRNAs within small dorsal root ganglion (DRG) neurons, which include nociceptive cells. Moreover, several DRG neuron-specific sodium channels now have been cloned and sequenced. After injury to the axons of DRG neurons, there is a dramatic change in sodium channel expression in these cells, with down-regulation of some sodium channel genes and up-regulation of another, previously silent sodium channel gene.

Dear Roz -

That last little article you posted is very cool, and it links with a bunch of interesting stuff. Thank you very much for posting it.

That said, this article, first presented at a National Academy of Sciences colloquium "The Neurobiology of Pain," held December 11-13, 1998, at the Arnold and Mabel Beckman Center in Irvine, CA, serves once again as a sad reminder of the 15 to 20 year lag time between basic research and FDA approval of new classes of medications.

Mike

Hi Mike,

Maybe if we were horses we would be healed by now.

Article from are neck of the woods.

http://www.signonsandiego.com/news/b...i21harman.html

Hugs, Roz

Hi Rosie,
Thanks for thanking me. But I should thank you, you always inspire me.

You are such a joy.
Hugs, Roz

Thanks for the interesting article- I dont agree with their prognosis data though
Oaklander pointed out that she never sees geriatric patients with CRPS; the average age of most patients is about 40, and the prevalence decreases as patients age. "These kind of epidemiologic data are consistent with a disease that does not last forever," she said. "It's one of the things that keeps me optimistic."

Could that be because we dont make it to Geriatric age??

Deb

Dear Deb -

If the relationship between CRPS and Interleukin 6 holds up then I too fear that you are dead on the money, so to speak. That said, you should be aware that the most recent study was not quite as conclusive as the first. See "Changes in immune and glial markers in the CSF of patients with Complex Regional Pain Syndrome," Guillermo M. Alexander, Marielle J. Perreault, Erin R. Reichenberger, Robert J. Schwartzman, Brain Behav. Immun. (2006), doi:10.1016/j.bbi.2006.10.009:

Abstract

Complex Regional Pain Syndrome is a severe chronic pain condition characterized by sensory, autonomic, motor and dystrophic signs and symptoms. The pain in CRPS is continuous, it worsens over time, and it is usually disproportionate to the severity and duration of the inciting event. This study compares cerebrospinal fluid (CSF) levels of pro- and anti-inflammatory cytokines, chemokines and several biochemical factors (glial fibrillary acidic protein (GFAP), the nitric oxide metabolites (nitrate plus nitrite), the excitatory amino acid neurotransmitter glutamate, calcium, total protein and glucose) in patients afflicted with CRPS to levels found in patients suffering with other non-painful or painful conditions. The aim of the study is to determine the degree of involvement of glial cells and immune system mediators in the pathophysiology of CRPS. There was no elevation or reduction of a CSF marker that was specific for CRPS patients. However, there were several patterns of markers that could be helpful in both elucidating the mechanisms involved in the disease process and supporting the diagnosis of CRPS. The most common pattern was found in 50% (11 out of 22) of the CRPS patients and consisted of; elevated IL-6, low levels of IL-4or IL-10, increased GFAP or MCP1 and increases in at least two of the following markers NO metabolites, calcium or glutamate. The results from this and other similar studies may aid in elucidating the mechanisms involved in the pathophysiology of CRPS. A better understanding of these mechanisms may lead to novel treatments for this very severe, life-altering illness.

(I will be happy to email anyone a copy of this study that wants to see it; just send me a pm with your email address.)

For the earlier study by largely the same authors, showing a stronger link between IL6 and CRPS, see "Changes in Cerebrospinal Fluid Levels of Pro-inflammatory Cytokines in CRPS," Alexander GM, van Rijn MA, van Hilten JJ, Perreault MJ, Schwartzmann RJ, Pain. 2005; 116:213-219 (finding of significant increases in interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the CSF of patients with CRPS-I: the mean CSF value of IL-6 in the CRPS group was significantly more (P < 0.005) than that seen in the control group; CSF level of IL-6 in all patients exceeded the sensitivity (0.039 pg/ml) of the ELISA assay by a factor of at least 25) [free full text pdf file accessible on RSDSA Medical Articles Archive, alphabetically listed by author under "Research" heading at http://www.rsds.org/2/library/articl...ve/index.html].

Finally, for the most depressing link between IL6 and coronary heart disease, see, e.g., "Relative Value of Multiple Plasma Biomarkers as Risk Factors for Coronary Artery Disease and Death in an Angiography Cohort," Kenny W.J. Lee, at al., Canadian Medical Association Journal, 2006 February 14; 174(4): 461– 466 (identifying IL-6 as one of the strongest independent predictors of CAD-related death) [for free full text pdf file, block and copy title of article and search PubMed at http://www.pubmedcentral.gov/].

Mike