*Pain exposure* physical therapy versus standard therapy for patients with complex regional pain syndrome type 1 (CRPS-1)

Complex Regional Pain Syndrome Type 1 (CRPS-1) is a term describing a variety
of painful conditions following injury which appears regionally having a distal
predominance of abnormal findings, exceeding in both magnitude and duration the
expected clinical course of the inciting event, often resulting in impairments
of movement-related functions, sensory functions and pain, and showing a
variable progression in the course of time. Patients with CRPS in whom a
peripheral nerve disorder can be confirmed are classified as type 2 (CRPS-2).
CRPS-1 has been a disastrous diagnosis in The Netherlands since decades,
resulting in 1988 in the founding of the largest patient platform in the world
after the United States with almost 4000 members. This is mainly due to the
chronification of currently 20.000 patients with an assumed 8000 new patients
per year. Current usual treatment results only in approximately 50% reduction
of pain, disabilities and restrictions in participation in patients with CRPS-1
after long follow-up and therefore cannot be qualified as highly effective. It
contributes to chronification and subsequent high costs which is an accepted
phenomena in CRPS patients. PEPT is expected to result in remarkably better
functioning and less pain in patients with CRPS-1. It is focused on full
recovery of functioning in a relatively short time. Long-lasting disabilities
and participation problems are not to be expected but rather early return to
work and social participation. PEPT is therefore a very low-cost approach,
which potential success for patients who are motivated to regain functioning
and temporarily neglect pain.

Despite a lacking scientific argumentation, the PEPT approach or Macedonian
therapy, is now being adopted on a large scale among physical therapists in The
Netherlands for patients with CRPS-1. There are two level C retrospective
cohort studies demonstrating a promising and clinical relevant beneficial
effect on pain and function after PEPT. In response to the growing demand for
scientific argumentation among doctors and physical therapists with respect to
the efficacy of PEPT, we conducted a pilot study at the UMC St Radboud
Nijmegen. The results of this pilot study were very promising and therefore, we
decided to design a large RCT to investigate the treatment effects and costs in
CRPS patients treated with PEPT compared to CRPS patients treated with usual
therapy according to the Dutch CBO guidelines.

Prospective, single-blinded, randomized clinical trial.
After base-line measurements (T0), measurements are performed at three (T1) and
six months (T2) after inclusion. Follow-up is at nine months (T3).

Treatment group: In the treatment group medication prescribed for CRPS is
tapered to zero. No invasive treatments like sympathetic blocks, and/or
operations will be performed. After extensive information about the mechanism
of action of PEPT in relation to CRPS, patients receive five sessions of PEPT
including homework exercises. The basic of PEPT is a function-oriented exercise
therapy. The PEPT physical therapist manipulates restricted joints and
intensively trains functional skills irrespective of pain experience during or
after the therapy. Patients are stimulated to use an active coping style to
achieve a clear functional goal in 5 sessions.
Control group: Usual treatment of CRPS-1 according to the Dutch CBO CRPS
guideline 2006 including, analgesics (WHO pain ladder), neuropathic drugs,
N-acetylcysteine, calcium channel blocker, ketanserine and DMSO
(dimethylsulphoxide). On indication, percutaneous sympathetic blocks or spinal
cord stimulation will be performed according to this CBO guideline. In
addition, patients receive physical therapy with exercises within pain limits
(pain contingent), splints and if necessary, aids for ADL activities.

In a consecutive inhomogeneous series of 87 patients with both acute and
chronic CRPS-1, who were all motivated to start with PEPT treatment in our
department of physical therapy, 20 patients (23%) stopped during the course of
the treatment. Ten patients decided to stop because of a lack of motivation
after all and ten other patients stopped when the treatment was interrogated by
other (medical) treatments. No single patient ceased because of exacerbation of
CRPS-1. Although we expect that in a more homogenous patient group this
percentage will decrease, in this study, 23% will be calculated as drop-out.