Evidence-based Review of Neuromodulaton Treatments in CRPS: A Crisis of Data, A Crisis of Faith

This is an odd and interesting article.  It's honest and, to my understanding of things, a fair assessment of where we are at in available, actual CRPS neuromodulation treatments, of which I am not a fan, awaiting, like many, some evidence.  This is a kind of rubber-meets-the-road piece, beginning and ending with the usual lament of LACK OF EVIDENCE.  Clearly, it's going to be a long while before evidence-based practices will be scientifically established for this God-forsaken disease.  The full text is available in RSDSA.org's excellent research library, and you can access it (and download it) HERE.

Neuromodulation: Technology at the Neural Interface
(onlinelibrary.wiley.com) DOI: 10.1111/j.1525-1403.2012.00531.x

FROM THE EDITOR-IN-CHIEF -- Robert M. Levy, MD, PhD
Evidence-Based Review of
Neuromodulation for Complex
Regional Pain Syndrome:
A Conflict Between Faith
and Science?

While it was more than 20 years ago, I remember well the face of
a 19-year-old woman who presented to me with what was then
called reflex sympathetic dystrophy (RSD). Having sustained an
innocuous injury during gymnastics practice four years earlier,
Susan developed discoloration, swelling, and severe burning pain in
her foot and leg. Aggressive rehabilitation therapy, pharmacotherapy,
and even sympathectomy had failed to improve her symptoms.
A trial of spinal cord stimulation (SCS) was highly successful
and a permanent system was implanted with complete relief of her
pain and resolution of her symptoms. Most memorable to me was
that she returned seven years later, symptom free, requesting that
her stimulator be removed prior to her planned pregnancy. The
smile on her face as she held her newborn child was the only testament
that I needed to convincemyself of the efficacy of SCS for RSD.
Since that time, I have had many successes and more than a few
failures of SCS for what is now known as complex regional pain
syndrome (CRPS). We have developed new stimulation techniques,
including high-frequency and intraspinal nerve root stimulation, to
rescue the therapy in patients who were no longer obtaining relief.
Nonetheless, I remained a strong believer in the value of SCS for
CRPS, both due to my personal anecdotal experience and the
support of at least one randomized, controlled clinical trial (1).
CRPS is characterized by continuous, intense pain out of proportion
to the severity of an injury, if any has been identified, which
tends to get worse over time. Typical features include changes in
color and temperature of the affected limb(s) accompanied by
intense burning pain, skin sensitivity, sweating, and swelling (2).
CRPS type I occurs in the setting of a soft tissue injury, while CRPS
type II develops following nerve injury. Of particular note is that
neuromodulation therapies are widely considered to be valuable
therapies for medically refractory CRPS. In fact, the website of the
National Institute of Neurologic Diseases and Stroke states that
“Spinal cord stimulation. . .appears to help many patients with their
pain” and that “Intrathecal drug pump. . .decreases side effects and
increases drug effectiveness” (Figs. 1 and 2) (2).
It was with this mindset that I approached a recent satellite conference
of the International Association of the Study of Pain (IASP)
Meeting in Milan, Italy. Organized by Drs. Joshua Prager, Michael
Stanton-Hicks, and Candy McCabe, “A Comprehensive Analysis of
CRPS Treatment: The New, The Old,WhatWorks and What Doesn’t—
Updating the Treatment Algorithm” was an IASP Pain and Sympathetic
Nervous System Special Interest Group symposium and CRPS
guidelines update meeting (Figs. 3–5).
With the participation of such august clinicians and neuroscientists
as Ralf Baron, Frank Huygen, Srinivasa Raja, and J.J. Van Hilten,
to name a few, this conference promised to be critically important
for the direction of CRPS research and therapy for many years to
come. I was honored to have been invited to critically review and
present the data supporting neuromodulation therapies for CRPS.
In performing a formal, evidence-based review of the literature, I
expected that an objective and impartial evaluation would fully
support my strongly held personal beliefs of the efficacy of neuromodulation
therapies for CRPS. Suffice it to say that my faith was

seriously challenged.

[He goes on to do an evidence-based review of neuromodulation modalities in treating CRPS, in each case coming up with insufficient, or no, satisfactory studies to support evidence-based conclusions]

PERIPHERAL NERVE FIELD

STIMULATION (PNfS)

PERIPHERAL NERVE STIMULATION (PNS)

SPINAL COLUMN

STIMULATION (SCS)

DEEP BRAIN STIMULATION (DBS)

MOTOR CORTEXT

STIMULATION (MCS)

INTRATHECAL DRUG DELIVERY (ITDD)

NON-NEUROMODULATION THERAPIES

FOR CRPS

CONCLUSIONS
I come back to the subtitle of this article: a conflict between faith
and science. I have great personal faith that in carefully selected
patients, neurostimulation and ITDD can be effective treatments for
the pain and spasticity related to CRPS. To be completely honest, I
also have great faith that in some patients, neuromodulation helps
neither of these CRPS symptoms. However, we are left with a gap
between our faith and our science. I routinely recommend that we
assess our therapies with the same critical eye as those who do not
believe in the effectiveness of neuromodulation therapies. Those of
us immersed in the field of neuromodulation often look askance at
the literature supporting sympathectomy for CRPS; however, we
have seen that the literature support for both interventions is seriously
flawed.
While a lack of evidence is not a lack of effectiveness, it remains
a lack of evidence. When our patients, our society, and our reimbursement
systems all demand evidence-based support of our
clinical practice, we cannot ignore the fact that there is inadequate
evidence to highly recommend most neuromodulation therapies
for CRPS. Some issues cannot be scientifically proven, and in those
cases we must rely upon our faith for guidance. The efficacy of
neuromodulation therapies for CRPS is, however, something that
can be proven or disproven. We have come a long way toward this
goal over the past decade, but we have much more to do. External
funding agencies, including the National Institutes of Health, have
expressed a renewed interest in supporting comparative outcomes
and cost-effectiveness research. By taking advantage of
these opportunities and supporting properly designed, carefully
executed studies, we can finally answer these questions and
improve the effectiveness of chronic pain therapy.
Robert M. Levy, MD, PhD

Editor-in-Chief