[fmichael]

This is perhaps the single most important article I've seen thus far.

It does nothing less than give strong evidence of a link between the mechanism of pro-inflammatory cytokines (including IL6) with vasodilation in patients with chronic CRPS-1. Or as set forth in the abstract, "the aim of [the] study was to determine the involvement of vasoactive substances endothelin-1 (ET-1) and nitric oxide (NO) during early chronic CRPS1."

From the "discussion" portion of the article:

In a previous study we observed that treatment with anti-TNF-α initiates recovery during the inflammatory stage of CRPS1. The effect of this intervention on the release of ET-1 and NOx is still unclear. Assuming a diminished blood flow, inhibition of the NO synthase is not advisable; on the contrary, NO donors should be supplemented. Besides the smooth muscle constrictive effects of ET-1, hyperalgesia and pain could also be the result of ET receptor stimulation. Therefore, specific ETA receptor antagonists (such as atrasentan) could provide remission. In pulmonary arterial hypertension, after treatment with the ET receptor antagonist bosentan, the suppression of NO synthesis was abolished and reversed to normal values of controls.

During the acute stage of CRPS1 large amounts of NO will be formed through activation of the inducible NO synthetase (iNOS). In that stage, the blood distribution has been increased which causes an increase of local skin temperature. In the endothelial cell [from the endothelium, "the layer of epithelial cells that lines the cavities of the heart and of the blood and lymph vessels and the serous cavities of the body, originating from the mesoderm"] NO will be formed from L-arginine through eNOS activation. Formation of NO could also occur after receptor stimulated activation of constitutive NOS (cNOS) or activation of neuronal NOS (nNOS) in nerve endings. In all cases this will result in increased vasodilation. TNF-α counteracts the activation of eNOS, whereas induction of iNOS in smooth muscle cells will be stimulated to generate NO. In the trophic phase of CRPS1 there will be a decline in the contribution of inflammatory mediators. Consequently, in combination with disuse of the extremity, less NO could be generated, resulting in diminished basal relaxation and retarded blood distribution, after which signs of the 'cold dystrophy' will become apparent.
[Citations omitted.]

Check it out. "Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1," J. George Groeneweg , et al, BMC Musculoskelet Disord., (2006) 7: 91. 2006 November 30

http://www.pubmedcentral.nih.gov/art...medid=17137491

Mike

Mike,
I hope you don't mind but I am going to put both of these articles at the TOS site. Hugs, Roz

[fmichael]

Roz -

Be my guest. The article is the closest thing to the Holy Grail I’ve come across since this whole thing started. First, it utilizes a relatively new and completely noninvasive method for measuring levels of IL6 in patients with “early chronic” CRPS-1; then it demonstrates a significant relationship between CRPS and a couple of pro-inflammatory cytokines, including IL6; and then gives strong evidence of a link between those cytokines and the mechanism of vasodilation (or constriction as the case may be) in patients with CRPS-1.

As set forth in the abstract, and to repeat myself as to the first of the three following sentences:

The aim of this study was to determine the involvement of vasoactive substances endothelin-1 (ET-1) and nitric oxide (NO) during early chronic CRPS1.

* * *

Results: The levels of IL-6, TNF-α and ET-1 in blister fluid in the CRPS1 extremity versus the contralateral extremity were significantly increased and correlated with each other, whereas NOx levels were decreased.

Conclusion: The NOx/ET-1 ratio appears to be disturbed in the intermediate stage of CRPS, resulting in vasoconstriction and consequently in a diminished tissue blood distribution.

I think I’m ready for some cytokine testing.

Mike

Hi Mike,
I had the ELISA test, on the second article it brings it up some. Mine came up Inc. (inclusive). I had to wait a couple weeks for that test, I was hopeing something would show up. Hugs, Roz