Monday, September 3, 2012

Neuroinflammation and Neuroautoimmunity in CRPS

graphic courtesy of CRPS UK

All I can say is that I have been waiting for this article for a long time, without even knowing it.  Available in its entirety through Springerlink, I encourage anyone struggling with explanations for "neuroinflammatory" symptoms/progression in their experience with CRPS to read it, and pass it on to their doctors.

Once again, we see His Holy Turd, Ochoa, invoked early on -- as most movement disorders, etc. -- shoot, as almost all symptoms of CRPS are psychogenic, according to this man owned by the forensic wing of Worlers Compensation.

The authors do the best thing in debunking him and those perplexed by much of the symptomology of CRPS -- which for too long has been called a diagnosis of exclusion.  That is just no longer true, not with the wealth of testing and nerve sampling that has finally caught up with the courtroom idiots.

In any event, "Neuroinflammation, Neuroautoimmunity, and the Co-Morbidities of Complex Regional Pain Syndrome," by Mark S. Cooper & Vincent P. Clark, published August 27, 2012 in the Journal of NeuroImmune Pharmacology -- is published online with open access, and God bless those making such infrequent gestures.

About the authors:

M. S. Cooper (*)
Department of Biology, University of Washington,
Seattle, WA 98195-1800, USA

V. P. Clark
Departments of Psychology and Neurosciences,
University of New Mexico,
Albuquerque, NM 87131-0001, USA

V. P. Clark
Mind Research Network
and Lovelace Biomedical Research Institute,
Albuquerque, NM 87106, USA

Here's a bit from the intro, and I encourage anyone with CRPS to make a copy of the article, and share it with your health care providers. As you can tell, I really think this is where the most meaningful research is heading.  (And lest anyone ever start to forget, Jose Ochoa is still a medical fraud and a bona fide turd -- in my humble and neutral opinion.)

Complex Regional Pain Syndrome (CRPS), formerly referred
to as Reflex Sympathetic Dystrophy (RSD), is one of the
diseases classically defined as hysteria minor by the early
neurologist, Dr. Jean-Martin Charcot (1892). To this day, the
sensory disorders and movement disorders of CRPS are sometimes
diagnosed as somatization disorders, or conversion disorders,
respectively (Ochoa and Verdugo 1995; Verdugo and
Ochoa 2000; Hawley and Weiner 2011). Such somatoform
disorders are defined as a chronic condition where physical
symptoms are observed, but no physical cause can be found
(Stone et al. 2011). In the absence of medical explanations for
the symptoms, a psychological etiology is presumed (Stone et
al. 2009, Stone et al. 2010).
In contrast to these views, substantial evidence has been
obtained that CRPS is a neuroinflammatory disorder, with a
probable autoimmune component in many individuals (Blaes et
al. 2007, Goebel et al. 2011; Kohr et al. 2011; Goebel 2011). In
a study of adult CRPS patients, 90% of the cohort had autoantibodies
to either the beta(2)-adrenergic receptor (β2AR) or the
muscarinic acetylcholine receptor (M2R) (Kohr et al. 2011).

55%of the patients had autoantibodies to both neurotransmitter
receptors. [...]

Achieving a cellular and molecular understanding of the
clinical progression of CRPS, as well as the generation of its
complex symptoms, requires modeling of the immunologic
and integrative physiology involved. It is important to consider
how distressed neurons and glial cells release factors
that stimulate the extravasation of leukocytes and autoantibodies,
from the bloodstream, into the parenchyma of the
CNS (Watkins et al. 2007). Serious neuroinflammatory consequences
would be expected to arise when β2AR and M2R
autoantibodies exudate from blood vessels, together with
complement proteins and leukocytes (Figs. 1 and 2).
Beggs et al. (2010) have recently found that the blood–brain
barrier in the spinal cord of rats is transiently compromised in
response to peripheral nerve injury. Extravasation of leukocytes
into the parenchyma of the cord has been found to last for
several days following a sciatic nerve injury (Milligan ED,
personal communication). In a CRPS patient with a peripheral
nerve injury, one might expect circulating autoantibodies to
exudate into the parenchyma of the injured nerve. Autoimmune
attack on peripheral nerves might trigger leukocyte extravasation,
autoantibody exudation, and neuroimmune activation in
the spinal cord as well. Neuroinflammation in the cord could
produce a mixture of pain, autonomic dysfunctions, somatovisceral
dysfunctions, and/or abnormal motor functions. CRPS
is a neurological disorder where many of these dysfunctions
can be expressed in a single patient (Schwartzman et al. 2009).
Vascular breakdown or leakage may be a critical step in
allowing autoantibodies access to the neuroautoantigens of
CRPS patients. Focal accumulations of neuroautoantibodies
on target cells are likely to initiate neuroinflammatory
responses. Whether the antibody-initiated neuroinflammation
remains as discrete foci, or whether the neuroinflammation
begins to propagate through the neuraxis, are key
questions for understanding the chronicity and spread of
CRPS symptoms in a given patient. CRPS shows distinctive
patterns of spread throughout the body (van Hilten et al.
2001; van Rijn et al. 2011). Spread of CRPS symptoms to
other body sites often occurs in a contiguous fashion. However,
it is possible for CRPS symptoms to appear quickly in
non-contiguous locations (van Hilten et al. 2001). Both
types of CRPS spreading behavior could be linked to the
establishment and spread of neuroinflammation within the
neuraxis. At this point in time, how CRPS symptoms spread
within the neuraxis is primarily known from an analysis at
the symptom level. Cellular and molecular knowledge about
the spread of neuroinflammation within the neuraxis in other
disorders comes from the neuroimaging of human patients,
as well as from animal model studies of neuropathic pain.

That ought to prime the pump of your interest... and what is especially helpful to me are the sections on movement disorders, since, yes, I am still spending much time in screaming mode, feeling powerless over the spasms and contortions in my legs.  Also, odds are good that if I pick something up, I will be retrieving it from the floor in short order.

It gets old!



    Hope this link works. It is to the British newspaper Daily Telegraph. I thought you may find it of some interest.

  2. thanks for that reference, emmaroyds. trigeminal neuralgia is another example of nasty neuropathic pains.

    pain as the fifth vital sign has been standard in the usa for a while but i think it is treated mostly as an annoyance and a joke by health care professionals. at least, that's been my experience.

    part of the problem is a patient's tendency to exaggeration, as in "my pain is a 20 out of 10..." -- which both conveys no useful information and also undermines the next patient who tries to be circumspect with a "9 out of 10"!

    but there are great health care professionals out there, quite capable of assessing pain via bp, pulse, and dozens of other more objective criteria.

    thanks for dropping by... and i hope you'll come visit again.

  3. Very interesting - makes me wonder if any of the immunosuppresive drugs might help.


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