CRPS in the Context of (Neuro?) Autoimmunity (With Thanks to Mice)

The study suggests Complex Regional Pain Syndrome 

could be caused by harmful serum-autoantibodies

Researchers at the University of Liverpool have taken a major step forward in understanding the causes of a disorder which causes chronic pain in sufferers. 

Complex Regional Pain Syndrome (CRPS) is a serious condition affecting a limb after an – often small – accident or operation.  It can cause severe pain lasting many years, as well as limb swelling, hair and nail growth changes, and muscle atrophy, but until now there has been no clear evidence of the cause. 

Now the research team from the University’s Institute of Translational Medicine alongside colleagues at the University of Pécs, Hungary have successfully transferred antibodies from the serum of patients with CRPS to mice, causing many of the same symptoms to be replicated. 

Dr Andreas Goebel *, who works in the University of Liverpool and is a Consultant in Pain Medicine at The Walton Centre NHS Foundation Trust, led the study.  He said: “CRPS is a serious condition which isn’t fully understood.  The findings of this study hint at a cause for it – harmful serum-autoantibodies – and raise the possibility of finding a treatment.”

[Read more of the story HERE from HealthCanal - Health News]
[ * Dr. Goebel's considerable research in chronic pain and CRPS HERE]

What to say?  It sounds momentous, yes?  But really, quite a bit of research, years old already, has been done that points to "clear evidence of the cause." Unfortunately, "THE cause" sort of thinking goes hand-in-hand with the "Silver Bullet Cure" crowd, and denies the complexity of the "syndrome." Be that as it may, it's a reflection more on the dumbing-down of pseudo-medical journalism, and not a reflection on the quality or bounds of the research on which the article is "reporting."

Why, for instance, do proponents of immunological causation feel the need to ignore the brain?  Just thought I'd toss that out there, as something not particularly helpful, but indicative of either/or thinking that just does not fly when dealing with the intricate relations and processes of the human body.  The peripheral and central nervous systems and their functional counterparts as parasympathetic and sympathetic impulses/small fibre neuropathy/glands run amok (hypothalamic-pituitary-adrenal -- HPA -- axis dysfunction)/immune system dysfunction/inflammation/psychosocial and environmental influences/and the darned partridge in a pear tree.

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A CRPS-IgG-transfer-trauma model reproducing inflammatory 

and positive sensory signs associated with complex regional pain syndrome

ABSTRACT
The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8 days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS.

An interesting site:  Centre for Immune Studies in Chronic Pain

© 2013 L. Ryan

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
e-mail: mscooper@u.washington.edu

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!