Recent CRPS Research

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I'm not feeling much like blogging these days, being about as busy as a body can be hosting Tête de Hergé's most anticipated Pity Party of the 2011 season.  Nonetheless, having run across some interesting newly published research, I did some wicked-fast copying and pasting, cogitating and perusing, and hope that you will find some of this CRPS work helpful and interesting.  I confess to having focused on aspects of this Sucky Disorder that are posing a challenge and raising questions in my life at present:  sensory dysfunction, disorder of body schema, hemilateral sensory disturbances, dystonia, and -- what the heck! -- ketamine induced liver injury!

There is some comfort in noting the many articles and topics being published and discussed -- just not enough comfort to warrant ending the Pity Party.  Maybe come August.  (Actually, ManorFest is about a week away, at which time my rabid navel-gazing will no longer be tolerated around here.  Already, people are strumming their fingers and rolling their eyes at my wailing and cultivated introspection.  I saw a preliminary ManorFest schedule in which I am relegated to working night shifts, exclusively, far from the public eye.  Harrumph.)

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Title
Comparable disorder of the body schema in patients with complex regional pain syndrome (CRPS) and phantom pain.

Author(s)
Reinersmann A, Haarmeyer GS, Blankenburg M, Frettlöh J, Krumova EK, Ocklenburg S, Maier C

Institution
Abteilung für Schmerztherapie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH Bochum, Ruhr-Universität Bochum, Bochum, Deutschland, annika.reinersmann@rub.de.

Source
Schmerz 2011 Jul 9.

Abstract
In patients with complex regional pain syndrome (CRPS) a disruption of the body schema has been shown in an altered cortical representation of the hand and in delayed reaction times (RT) in the hand laterality recognition task. However, the role of attentional processes or the effect of isolated limb laterality training has not yet been clarified.The performance of healthy subjects (n=38), CRPS patients (n=12) and phantom limb pain (PLP) patients (n=12) in a test battery of attentional performance (TAP) and in a limb laterality recognition task was compared and the effect of limb laterality training in CRPS patients and healthy subjects evaluated.The RTs of both CRPS and PLP patients were significantly slower than those of healthy subjects despite normal TAP values. The CRPS and PLP patients showed bilaterally delayed RTs. Through training RTs improved significantly but the RTs of CRPS patients remained slower than those of healthy subjects. In this study an equal disruption of the body schema was found in both CRPS and PLP patients which cannot be accounted for by attentional processes. For CRPS patients this disorder cannot be fully reversed by isolated limb laterality recognition training.

Language
GER

PubMed ID
21739258

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Title
Impaired Hand Size Estimation in CRPS.

Author(s)
Peltz E, Seifert F, Lanz S, Müller R, Maihöfner C

Institution
Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Source
J Pain 2011 Jul 7.

Abstract
A triad of clinical symptoms, ie, autonomic, motor and sensory dysfunctions, characterizes complex regional pain syndromes (CRPS). Sensory dysfunction comprises sensory loss or spontaneous and stimulus-evoked pain. Furthermore, a disturbance in the body schema may occur. In the present study, patients with CRPS of the upper extremity and healthy controls estimated their hand sizes on the basis of expanded or compressed schematic drawings of hands. In patients with CRPS we found an impairment in accurate hand size estimation; patients estimated their own CRPS-affected hand to be larger than it actually was when measured objectively. Moreover, overestimation correlated significantly with disease duration, neglect score, and increase of two-point-discrimination-thresholds (TPDT) compared to the unaffected hand and to control subjects' estimations. In line with previous functional imaging studies in CRPS patients demonstrating changes in central somatotopic maps, we suggest an involvement of the central nervous system in this disruption of the body schema. Potential cortical areas may be the primary somatosensory and posterior parietal cortices, which have been proposed to play a critical role in integrating visuospatial information. PERSPECTIVE: CRPS patients perceive their affected hand to be bigger than it is. The magnitude of this overestimation correlates with disease duration, decreased tactile thresholds, and neglect-score. Suggesting a disrupted body schema as the source of this impairment, our findings corroborate the current assumption of a CNS involvement in CRPS.

PubMed ID
21741321

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Title
The Specificity and Mechanisms of Hemilateral Sensory Disturbances in Complex Regional Pain Syndrome.

Author(s)
Knudsen L, Finch PM, Drummond PD

Institution
School of Psychology, Murdoch University, Perth, Western Australia.

Source
J Pain 2011 Jun 22.

Abstract
Hyperalgesia often extends from the affected limb to the ipsilateral forehead in patients with complex regional pain syndrome (CRPS). To investigate whether this is more common in CRPS than other chronic pain conditions, pressure-pain thresholds and sharpness to a firm bristle were assessed on each side of the forehead, at the pain site, and at an equivalent site on the contralateral side in 32 patients with chronic pain other than CRPS (neuropathic or nociceptive limb pain, radicular pain with referral to a lower limb or postherpetic neuralgia), and in 34 patients with CRPS. Ipsilateral forehead hyperalgesia to pressure pain was detected in 59% of CRPS patients compared with only 13% of patients with other forms of chronic pain. Immersion of the CRPS-affected limb in painfully cold water increased forehead sensitivity to pressure, especially ipsilaterally, whereas painful stimulation of the healthy limb reduced forehead sensitivity to pressure pain (albeit less efficiently than in healthy controls). In addition, auditory discomfort and increases in pain in the CRPS-affected limb were greater after acoustic startle to the ear on the affected than unaffected side. These findings indicate that generalized and hemilateral pain control mechanisms are disrupted in CRPS, and that multisensory integrative processes may be compromised. PERSPECTIVE: The findings suggest that hemilateral hyperalgesia is specific to CRPS, which could be diagnostically important. Disruptions in pain-control mechanisms were associated with the development of hyperalgesia at sites remote from the CRPS limb. Addressing these mechanisms could potentially deter widespread hyperalgesia in CRPS.

PubMed ID
21703937

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Title
Fixed Dystonia in Complex Regional Pain Syndrome: a Descriptive and Computational Modeling Approach.

Author(s)
Munts AG, Mugge W, Meurs TS, Schouten AC, Marinus J, Moseley GL, van der Helm FC, van Hilten JJ

Source
BMC Neurol 2011 May 24; 11(1):53.

ABSTRACT:
BACKGROUND: Complex regional pain syndrome (CRPS) may occur after trauma, usually to one limb, and is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. Involvement of dysfunctional GABAergic interneurons has been suggested, however the mechanisms that underpin fixed dystonia are still unknown. We hypothesized that dystonia could be the result of aberrant proprioceptive reflex strengths of position, velocity or force feedback.
METHODS: We systematically characterized the pattern of dystonia in 85 CRPS-patients with dystonia according to the posture held at each joint of the affected limb. We compared the patterns with a neuromuscular computer model simulating aberrations of proprioceptive reflexes. The computer model consists of an antagonistic muscle pair with explicit contributions of the musculotendinous system and reflex pathways originating from muscle spindles and Golgi tendon organs, with time delays reflective of neural latencies. Three scenarios were simulated with the model: (i) increased reflex sensitivity (increased sensitivity of the agonistic and antagonistic reflex loops); (ii) imbalanced reflex sensitivity (increased sensitivity of the agonistic reflex loop); (iii) imbalanced reflex offset (an offset to the reflex output of the agonistic proprioceptors).
RESULTS: For the arm, fixed postures were present in 123 arms of 77 patients. The dominant pattern involved flexion of the fingers (116/123), the wrists (41/123) and elbows (38/123). For the leg, fixed postures were present in 114 legs of 77 patients. The dominant pattern was plantar flexion of the toes (55/114 legs), plantar flexion and inversion of the ankle (73/114) and flexion of the knee (55/114). Only the computer simulations of imbalanced reflex sensitivity to muscle force from Golgi tendon organs caused patterns that closely resembled the observed patient characteristics. In parallel experiments using robot manipulators we have shown that patients with dystonia were less able to adapt their force feedback strength.
CONCLUSIONS: Findings derived from a neuromuscular model suggest that aberrant force feedback regulation from Golgi tendon organs involving an inhibitory interneuron may underpin the typical fixed flexion postures in CRPS patients with dystonia.

PubMed ID
21609429

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Title
Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain in CRPS type 1 patients: A report of 3 cases.

Author(s)
Noppers IM, Niesters M, Aarts LP, Bauer MC, Drewes AM, Dahan A, Sarton EY

Institution
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.

Source
Pain 2011 May 3.

Abstract
Studies on the efficacy of ketamine in the treatment of chronic pain indicate that prolonged or repetitive infusions are required to ensure prolonged pain relief. Few studies address ketamine-induced toxicity. Here we present data on the occurrence of ketamine-induced liver injury during repeated administrations of S(+)-ketamine for treatment of chronic pain in patients with complex regional pain syndrome type 1 as part of a larger study exploring possible time frames for ketamine re-administration. Six patients were scheduled to receive 2 continuous intravenous 100-hour S(+)-ketamine infusions (infusion rate 10-20mg/h) separated by 16days. Three of these patients developed hepatotoxicity. Patient A, a 65-year-old woman, developed an itching rash and fever during her second exposure. Blood tests revealed elevated liver enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and γ-glutamyl transferase, all⩾3 times the upper limit of normal) and modestly increased eosinophilic leukocytes. Patient E, a 48-year-old woman, developed elevated liver enzymes of similar pattern as Patient A during her second ketamine administration and a weakly positive response to antinuclear antibodies. In a third patient, Patient F, a 46-year-old man, elevated liver enzymes (alanine transaminase and γ-glutamyl transferase) were detected on the first day of his second exposure. In all patients, the ketamine infusion was promptly terminated and the liver enzymes slowly returned to reference values within 2months. Our data suggest an increased risk for development of ketamine-induced liver injury when the infusion is prolonged and/or repeated within a short time frame. Regular measurements of liver function are therefore required during such treatments. During repeated ketamine infusion for treatment of CRPS1, three patients developed liver injury probably allergic in nature.

PubMed ID
21546160

Excuse me, have you seen my foot?

I am glad to be able to post the following new CRPS article, published in the journal Pain.

There is a bizarre phenomenon that can occur -- no surprise with such a funky disease, but still, I know I am loathe to talk about it. To do so makes a person sound completely nuts.

Sometimes I cannot help it, though, and have been known to cry out:

WHERE IS MY LEG?

It is often one of the first questions I ask of people I meet who have CRPS -- Do you ever lose your involved limbs in space? And lose them in space despite the fact that they are delivering enormous amounts of pain? Do you have to stop and look at your legs in order to have the confidence to try another step?

Of recent evolution in my Rhetorical Question Package is this:

WHERE THE HELL IS MY HAND?

Of course, like other aspects of CRPS, you can turn these little weirdnesses into cheap home entertainment. We haven't had to go to the movies or see a play or any of those boring activities -- for years! Not when you can prop my legs up on soft pillows, covered in that oft-mentioned high-density muscovite cotton weave, and watch them turn red, purple, white, and deep blue. Once spasticity sets in -- don't despair, it might take you a few years -- the color kaleidoscope gains a diverting twisting action that you will want to rate as you might the vault of an elite gymnast.

It's also fun to play "Guess how cold?" but for that you'll need one of those sticky skin thermometers.

And popcorn! Don't forget the popcorn!

PAIN: Journal of the International Association for the Study of Pain
Volume 149, Issue 3, Pages 463-469 (June 2010)
Authors/Researchers: Jennifer S. Lewis, Paula Kersten, Kathryn M. McPherson, Gordon J. Taylor, Nigel Harris, Candida S. McCabe, David R. Blake

Wherever is my arm? Impaired upper limb position accuracy in Complex Regional Pain Syndrome

ABSTRACT:

Knowledge of the position of one’s limbs is an essential component of daily function and relies on complex interactions of sensorimotor body schema-related information. Those with Complex Regional Pain Syndrome (CRPS) express difficulty in knowing where their affected limb is positioned. The aim of this study was to determine the degree to which experimental data supported the reported difficulty in limb position sense. A controlled experimental design was used to measure upper limb position accuracy amongst those with CRPS of one arm. Position accuracy was individually measured in both arms and compared to a known target position. Video captured each of 36 trials (half with arm in full view and half with vision obscured). The error in degrees between actual and known targets was determined using video analysis software. The Brief Pain Inventory measured pain. A subjective mental image representation of both upper limbs was documented. The CRPS group had moderate pain intensity and were significantly less accurate in positioning both the affected and unaffected limbs compared to controls (p less than 0.001).

You can access the entire article in .pdf here.

INTRODUCTION

‘‘If the pain is very intense, even if I am touching something else I’ve
got no idea where my arm exists” [27, p. 115]. This description typifies
the difficulty that those with CRPS express in knowing where
their affected limb is positioned [27]. Knowledge of the position of
one’s limbs plays an essential role within the motor system – enabling
accurate and smooth movements to be performed [13]
and is a necessary component of daily functioning [18]. This sense
involves a complex interaction of proprioceptive, vestibular,
somatosensory and visual inputs from the periphery that interrelate
with motor systems [13,19,22]. Interpretation of this multisensory
information within the context of a centrally maintained
representation of the limb or ‘body schema’ provides our fundamental
sense of limb position [21,22].

However, subjective perceptual disturbances of the affected
limb are suggestive of distortions in body schema amongst those
with CRPS. Features such as a desire to amputate [8,10,27], perceptual
distortions in size and shape [27,31,32], lack of self-ownership
[12,14,27] and hostile feelings [27] have all been expressed by
individuals about their affected limb. Cortical reorganisation in regions
associated with the body schema (i.e. primary somatosensory
cortex, posterior parietal lobe) have been revealed by brain
imaging, providing further evidence of body schema disruption
[28–30,34].

Given that limb position sense is integral to performing movements
it is important to note that motor dysfunction is well recognised
in CRPS [4,14,15,23,25,37,44–47]. Brain-imaging evidence of
altered neural activity in motor cortices has also been found [30].
Despite acknowledged changes in body perception and motor
function little is known about limb position sense and performance
in CRPS. As such the aim of this study was to determine the degree
to which objective experimental data supports the ‘sense’ or reported
perception of limb-positioning difficulty. We hypothesised
that there was a statistically significant difference in affected upper
limb position accuracy in those with CRPS when compared to
healthy volunteers. In addition, we wished to determine whether
there was a relationship between limb position accuracy and
self-perception of the affected limb. Given that vision of the limb
plays an important role in updating the body schema [9,11] we
aimed to establish the extent to which vision may contribute to
limb-positioning accuracy. By addressing these aspects we set
out to provide insights into the mechanisms of limb position performance
in CRPS and how this knowledge might inform clinical
practice.