[fmichael]

Attached for your consideration is a short article by Wilfrid Jänig, which succinctly reviews almost all of the known science around CRPS in 4 pages, beginning with the most significant advances in recent years.

In many respects, the article is a follow on to Jänig and Baron's Editorial, Is CRPS I a neuropathic pain syndrome? Pain 120 (2006) 227–229, http://www.rsds.org/2/library/articl...ogy%2006.pdfas as much as an invited "Commentary" on an article which will be published in the same issue: Bove, G.M., 2009. Focal nerve inflammation induces neuronal signs consistent with 262 symptoms of early complex regional pain syndromes. Exp. Neurol. 219, 223–227.

The 2009 article by Oaklander and Fields is noted in the conclusion below. That is a piece with which we all have to be familiar. Is reflex sympathetic dystrophy/complex regional pain syndrome type I a small-fiber neuropathy? Oaklander AL, Fields HL, Ann Neurol. 2009 Jun;65(6):629-38:

Abstract
Neurologist S. Weir Mitchell first described "causalgia" following wartime nerve injury, with its persistent distal limb burning pain, swelling, and abnormal skin color, temperature, and sweating. Similar post-traumatic symptoms were later identified in patients without overt nerve injuries after trauma. This was labeled reflex sympathetic dystrophy (RSD; now complex regional pain syndrome type I [CRPS-I]). The pathophysiology of symptoms is unknown and treatment options are limited. We propose that persistent RSD/CRPS-I is a post-traumatic neuralgia associated with distal degeneration of small-diameter peripheral axons. Small-fiber lesions are easily missed on examination and are undetected by standard electrophysiological testing. Most CRPS features-spreading pain and skin hypersensitivity, vasomotor instability, osteopenia, edema, and abnormal sweating-are explicable by small-fiber dysfunction. Small fibers sense pain and temperature but also regulate tissue function through neuroeffector actions. Indeed, small-fiber-predominant polyneuropathies cause CRPS-like abnormalities, and pathological studies of nerves from chronic CRPS-I patients confirm small-fiber-predominant pathology. Small distal nerve injuries in rodents reproduce many CRPS features, further supporting this hypothesis. CRPS symptoms likely reflect combined effects of axonal degeneration and plasticity, inappropriate firing and neurosecretion by residual axons, and denervation supersensitivity. The resulting tissue edema, hypoxia, and secondary central nervous system changes can exacerbate symptoms and perpetuate pathology. Restoring the interest of neurologists in RSD/CRPS should improve patient care and broaden our knowledge of small-fiber functions.

PMID: 19557864 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/1...m&ordinalpos=5

Nevertheless, I think that if there is a target in Jänig's article, it may be the positions expressed in Oaklander AL, RSD/CRPS: The end of the beginning (editorial) Pain. 2008, http://www.rsds.org/2/library/articl..._editorial.pdf. As set forth in the second page of Jänig's current article:

From the studies of Dr. Bove we do not learn about mechanisms underlying the following diverse observations made on CRPS patients that involve sympathetic, somatomotor and somatosensory (including nociceptive) systems and in particular the brain . . . . (Footnotes omitted.)

So what Dr. Jänig is saying is that while small fiber neuropathy may do a fine job of explaining the initial development of CRPS - if one can also incorporate the spinal column into the model - as well as the surge of inflamatory cytokines during the acute stage of the illness, the argument that many of the long term symptoms of chronic CRPS can be readily explained by small fiber neuropathies (including those very small nerve fibers that pass through - or "innervate" the walls of blood vessels) is simply not supported by current science. And these include observed physical changes to the brain itself, down to specific changes in regional cerebral blood flow (rCBF) - that no one has yet to remotely link with small fiber neuropathies, not that the connections are not there, but they have yet to be established. (Think of it as your basic dark energy problem.)

I just wish that in Jänig's discussion of all the areas that small fiber neuropathy theory currently cannot explain, he had referred to the brain studies coming out of Prof. Apkarian's "Pain and Pleasure Labratory" at Northwestern, including the most recent article of which I'm aware, Geha PY, Baliki MN, Harden RN, Bauer WR, Parrish TB, Apkarian AV, The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions: Neuron. 2008;60:570-581, http://www.rsds.org/2/library/articl...aliki_etal.pdf, where observed changes in the brains of CRPS patients were long dismissed by the small fiber neuropathy crowd and others as only demonstrating adaptive responses to chronic pain, a blanket assertion that was subsequently refuted in the Northwestern studies, demonstating that the brain on CRPS was not the same as the brain on chronic low back pain or Fibromyalgia.

I leave you with Dr. Jänig's conclusion and urge you to read the paper itself:

215 By mentioning these observations based on quantitative measure-
216 ments on CRPS patients, I want to emphasize that we have to be very
217 careful about trying to reduce this enigmatic pain disorder to a
218 peripheral pathophysiological process. I think that this was not the
219 intention of Dr. Bove. Two reviews published recently tend to argue
220 that CRPS is primarily a small-fiber neuropathy (Oaklander and Fields
221 2009) or an inflammatory disease (de Mos et al., 2009). I believe that
222 the peripheral changes (inflammatory changes, vascular changes,
223 edema, and trophic changes) cannot be seen independently of the
224 changes in the central nervous system including the spinal cord. Both
225 the central and peripheral nervous systems interact with each other
226 via afferent and efferent signals, some of which may not be electrical,
227 i.e. by impulses conducted in neurons, but by hormonal signals or by
228 changes of axoplasmic transport. The nature of this interaction
229 remains a puzzle. This conceptual approach may further our
230 understanding why CRPS can be triggered after trivial trauma, after
231 trauma remote from the affected extremity, possibly after immobili-
232 zation of an extremity, or following processes in the cerebral
233 hemispheres. It will explain why, in CRPS patients with SMP, a few
234 temporary blocks (and sometimes only one block!) of the sympathetic
235 supply to the affected extremity can sometimes lead to long-lasting
236 (even permanent) pain relief and to resolution of the other changes
237 present in CRPS. When seen from this perspective CRPS is a real
238 intellectual challenge for researchers working on humans or animals
239 (Jänig and Baron 2004, 2006). To unravel the mechanisms of this
240 fascinating disorder will keep us busy for several years to come. We
241 now have the tools to solve the problem.

Mike

[bassman]

Very succinct. I ran into two doctors recently who could benefit from this quick read.

Thanks,

Mike