[Sandel]

Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management.

http://www.biomedcentral.com/1471-2474/10/116

Quote:

Background
During the chronic stage of Complex Regional Pain Syndrome (CRPS), impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS.

Discussion
The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin.

End quote:

Hi,
This study discusses amongst other things the various pain states and what can cause them, exaberate them, and hopefully help.
It also sugests some newer treatments in their pharmacological section where they discuss the various new studies out and treatment regimes.

S.

[fmichael]

Dear Sandra -

Thanks for that. And I've read the article, Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management, George Groeneweg, Frank JPM Huygen, Terence J Coderre and Freek J Zijlstra, BMC Musculoskeletal Disorders 2009, 10:116, to which you link at http://www.biomedcentral.com/1471-2474/10/116

Unfortunately, this review article appears to have focused almost exclusively on studies comparing the blood flow in the "affected" limb with that of the "contralateral" [why not just say opposite(?)] limb, using that as a control, without taking into account the possibility that CRPS may - and almost certainly does - trigger systemic vascular changes. A limitation that was explicitly acknowledged in at least one of the articles cited in "Regulation of peripheral blood flow in Complex Regional Pain Syndrome, etc." See, Exaggerated vasoconstriction in complex regional pain syndrome-1 is associated with impaired resistance artery endothelial function and local vascular reflexes, Dayan L, Salman S, Norman D, Vatine JJ, Calif E, Jacob G, J Rheumatology 2008 Jul;35(7):1339-45 at 1344:

We compared one limb with its counterpart rather than with a normal subject’s limb. Although one cannot assume normalcy of the contralateral limb, the fact that CRPS tends to affect only one limb might indicate that local rather than systemic effectors dominate its pathogenesis.

I'll be happy to send a copy of the article to anyone interested.

It's my own view that documenting and understanding systemic vascular changes in CRPS is an essential prerequisite for developing effective therapies beyond the acute stage of the illness. And so far, there appears to be less written on the subject than I would have imagined going into this.

However, and in all fairness, some of this stuff is harder than Chinese algebra - to steal an out of context phrase from Tom Waits - where the mechnisms of action run all the way from the simple constriction of the blood vessels due to sympathetic overactivation or something as complicated as "arterial abnormalities characterized by an overall loss of PGP-positive innervation coupled with hypertrophic, multi-laminated vascular walls." Albrecht PH, Hines S, Eisenberg E, et al, Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with complex regional pain syndrome, Pain 2006;120:244-266, 259-263, full text with numerous and occasionally gruesome colored slides at http://www.rsds.org/2/library/articl..._PAIN%2006.pdf

I would be curious as to your thoughts on this.

Mike

[Sandel]

Hi Mike,

That link won't work for me.

I totaly agree with you about RSD being a systemic condition in most cases, I say most because there's a part of me that feels there are seperate forms of CRPS as well as the stages. Or mabie it is reversed and it is actualy something that causes the condition to stay in one specific region sometimes.
Either way treating the condition systemicly is smart, diagnosing the limb using the patients contralateral (yep "other") limb is dumb.

WCB used my left leg to diagnose my right leg with RSD.. I got the diagnosis because the right was so much "worse" than my left, WCB didn't believe in spread back then so the would not listen when I told them they both had RSD.

After my radial angeogram same thing both arms had mild RSD prior to surgery, after angeogram right arm blew up and they used left arm.. didn't get the diagnosis at first because was a bad flare day for the left arm, so I went back after it had settled and they could see how much worse the angeogram arm was and then I got the diagnosis.. a year later I got diagnosed with RSD in all 4 limbs BY WCB cource my doctors had already diagnosed me full body lol

I have always thought my RSD went systemic very fast.. cold too. very fast, spread easy like wildfire.

[fmichael]

Dear Sandra -

Thanks for the heads up on the link, which has been fixed.

My introduction to this topic also occured early on. I was in Phildelphia in February, 2002, maybe 19 months after this got going, for a 5-day lidocaine infusion, which required the insertion of a 3-lead catheter through a 20 guage needle. After a number of attempts, Dr. S. told the nurses to give up, saying that "the RSD [in my legs] has shut down his veins [in my arms]." At which point I had to wait (NPO) for a surgical team to show uo to put an old fashioned central line in my chest. The surgeons finally showed up the next day. (This in the days before PICC lines.)

Since then, whenever I have a study that requires anything but a very narrow iv line, such as a CT angiogram, if they're able to get it in, the iv invariably kinks by the time the contrast has to be delived in a precise period of time. Ditto thalium adenosine stress tests, in which I have been advised that I am "n of 1" in the history of the Nuclear Cardiology Dept. at Cedars Sinai in Los Angeles. I now just make an appointment with the PICC service beforehand and don't worry about it.

But the bigger point is this, if our small vessels are narrowing, that is likely to have some effects. For something that just blew me away, even though one has to keep in mind that it's based on a set of experimentally induced conditions, check out, Cutaneous tactile allodynia associated with microvascular dysfunction in muscle, Laferrière A, Millecamps M, Xanthos DN, Xiao WH, Siau C, de Mos M, Sachot C, Ragavendran JV, Huygen FJ, Bennett GJ, Coderre TJ, Molecular Pain, 2008 Oct 28;4:49, free full text at http://www.ncbi.nlm.nih.gov/entrez/u.../content/4//49

ABSTRACT:

BACKGROUND: Cutaneous tactile allodynia, or painful hypersensitivity to mechanical stimulation of the skin, is typically associated with neuropathic pain, although also present in chronic pain patients who do not have evidence of nerve injury. We examine whether deep tissue microvascular dysfunction, a feature common in chronic non-neuropathic pain, contributes to allodynia.

RESULTS: Persistent cutaneous allodynia is produced in rats following a hind paw ischemia-reperfusion injury that induces microvascular dysfunction, including arterial vasospasms and capillary slow flow/no-reflow, in muscle. Microvascular dysfunction leads to persistent muscle ischemia, a reduction of intraepidermal nerve fibers, and allodynia correlated with muscle ischemia, but not with skin nerve loss. The affected hind paw muscle shows lipid peroxidation, an upregulation of nuclear factor kappa B, and enhanced pro-inflammatory cytokines, while allodynia is relieved by agents that inhibit these alterations. Allodynia is increased, along with hind paw muscle lactate, when these rats exercise, and is reduced by an acid sensing ion channel antagonist.

CONCLUSION: Our results demonstrate how microvascular dysfunction and ischemia in muscle can play a critical role in the development of cutaneous allodynia, and encourage the study of how these mechanisms contribute to chronic pain. We anticipate that focus on the pain mechanisms associated with microvascular dysfunction in muscle will provide new effective treatments for chronic pain patients with cutaneous tactile allodynia. [Emphasis added.]

PMID: 18957097 [PubMed - indexed for MEDLINE]
PMCID: PMC2584041

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Finally, we have the anectodal resports of many people here, who facing one or more problem with an organ not commomly associated with CRPS, are told by their doctors, "It's the RSD." While I certainly am not in a position to evaluate those statements, if it is the RSD, wouldn't it make sense if a microcirculatory issue lay at it's heart? But not to worry, for if that's the case, capitalism may have come to the rescue, as in, ever heard of Cialis®? See, Effect of tadalafil on blood flow, pain, and function in chronic cold complex regional pain syndrome: a randomized controlled trial, Groeneweg G, Huygen FJ, Niehof SP, Wesseldijk F, Bussmann JB, Schasfoort FC, Stronks DL, Zijlstra FJ, BMC Musculoskeletal Disorder 2008 Oct 20;9:143, free full text at http://www.ncbi.nlm.nih.gov/entrez/u...471-2474/9/143

ABSTRACT:

BACKGROUND: This double-blind, randomized, controlled trial investigated the effect of the phosphodiesterase-5 inhibitor tadalafil on the microcirculation in patients with cold Complex Regional Pain Syndrome (CRPS) in one lower extremity.

METHODS: Twenty-four patients received 20 mg tadalafil or placebo daily for 12 weeks. The patients also participated in a physical therapy program. The primary outcome measure was temperature difference between the CRPS side and the contralateral side, determined by measuring the skin temperature with videothermography. Secondary outcomes were: pain measured on a Visual Analogue Scale, muscle force measured with a MicroFet 2 dynamometer, and level of activity measured with an Activity Monitor (AM) and walking tests.

RESULTS: At the end of the study period, the temperature asymmetry was not significantly reduced in the tadalafil group compared with the placebo group, but there was a significant and clinically relevant reduction of pain in the tadalafil group. Muscle force improved in both treatment groups and the AM revealed small, non-significant improvements in time spent standing, walking, and the number of short walking periods. CONCLUSION: Tadalafil may be a promising new treatment for patients that have chronic cold CRPS due to endothelial dysfunction, and deserves further investigation.

PMID: 18937830 [PubMed - indexed for MEDLINE] PMCID: PMC2575214

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

And that's about what I've got.

Mike