CRPS Research Update | October 2014 #CRPS

Welcome to the Complex Regional Pain Syndrome Research Update for October, a summary of the latest studies. 

If you are suffering with CRPS, I am here to show you how you can move forward — come and visit the CRPS clinic page here.

Spinal cord stimulation for complex regional pain syndrome type 1 with dystonia: a case report and discussion of the literature.
Voet C1, le Polain de Waroux B2, Forget P2, Deumens R3, Masquelier E4.

Complex Regional Pain Syndrome type 1 (CRPS-1) is a debilitating chronic pain disorder, the physiopathology of which can lead to dystonia associated with changes in the autonomic, central and peripheral nervous system. An interdisciplinary approach (pharmacological, interventional and psychological therapies in conjunction with a rehabilitation pathway) is central to progress towards pain reduction and restoration of function.
This case report aims to stimulate reflection and development of mechanism-based therapeutic strategies concerning CRPS associated with dystonia.
A 31 year old female CRPS-1 patient presented with dystonia of the right foot following ligamentoplasty for chronic ankle instability. She did not have a satisfactory response to the usual therapies. Multiple anesthetic blocks (popliteal, epidural and intrathecal) were not associated with significant anesthesia and analgesia. Mobilization of the foot by a physiotherapist was not possible. A multidisciplinary approach with psychological support, physiotherapy and spinal cord stimulation (SCS) brought pain relief, rehabilitation and improvement in the quality of life.
The present case report demonstrates the occurrence of multilevel (peripheral and central) pathological modifications in the nervous system of a CRPS-1 patient with dystonia. This conclusion is based on the patient’s pain being resistant to anesthetic blocks at different levels and the favourable, at least initially, response to SCS. The importance of the bio-psycho-social model is also suggested, permitting behavioural change

RS: With CRPS we absolutely need to consider ‘multilevel’ modifications and adaptations within the nervous system but also how all the other systems that have a role in protecting us are functioning. This often manifests as habitual thinking and activities that maintain protection. Realising these habits, automatic by the nature of being a habit, and making changes with specific training creates new patterns of activity that head towards health.


Longstanding Complex Regional Pain Syndrome is associated with activating autoantibodies against α-1a adrenoceptors.
Dubuis E1, Thompson V2, Leite MI3, Blaes F4, Maihöfner C5, Greensmith D6, Vincent A7, Shenker N8, Kuttikat A9, Leuwer M10, Goebel A11.

Complex Regional Pain Syndrome (CRPS) is a limb-confined post-traumatic pain syndrome with sympathetic features. The cause is unknown, but the results of a randomized crossover trial on low-dose IVIG treatment point to a possible autoimmune mechanism. We tested purified serum immunoglobulin G (IgG) from patients with longstanding CRPS for evidence of antibodies interacting with autonomic receptors on adult primary cardiomyocytes, comparing with control IgG from healthy and disease controls, and related the results to the clinical response to treatment with low-dose intravenous immunoglobulins (IvIG). We simultaneously recorded both single cell contractions and intracellular calcium handling in an electrical field. Ten of 18 CRPS preparations and only 1/57 control preparations (p<0.0001) increased the sensitivity of the myocytes to the electric field and this effect was abrogated by pre-incubation with alpha1a receptor blockers. By contrast, effects on baseline calcium were blocked by pre-incubation with atropine. Interestingly, serum-IgG preparations from all four CRPS patients who had responded to low-dose IVIG with meaningful pain relief were effective in these assays, although 4/8 of the non-responders were also active. To see if there were antibodies to the alpha1a receptor, CRPS-IgG was applied to alpha 1a receptor transfected rat1-fibroblast cells. The CRPS serum IgG induced calcium flux, and FACS showed that there was serum IgG binding to the cells. The results suggest that patients with longstanding CRPS have serum antibodies to alpha 1a receptors, and that measurement of these antibodies may be useful in the diagnosis and management of the patients.


A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome.
Tékus V1, Hajna Z1, Borbély É1, Markovics A1, Bagoly T1, Szolcsányi J2, Thompson V3, Kemény Á1, Helyes Z2, Goebel A4.

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 8days. 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.

RS – as ever we must consider the role of the immune system but in the light of other systems as no system works in isolation to the others. There is vast interaction between the immune system, nervous system, endocrine system and autonomic nervous system to the point where I believe we are a single system interpreting and responding. One response maybe pain as part of protection and our systems become very good at protecting us — this is not to suggest that our systems and ‘me’ are separate entities. Whole person is the only way we can sensibly think about this.

Local Anesthetic Sympathectomy Restores fMRI Cortical Maps in CRPS I after Upper Extremity Stellate Blockade: A Prospective Case Study.
Stude P, Enax-Krumova EK1, Lenz M, Lissek S, Nicolas V, Peters S, Westermann A, Tegenthoff M, Maier C.

Patients with complex regional pain syndrome type I (CRPS I) show a cortical reorganization with contralateral shrinkage of cortical maps in S1. The relevance of pain and disuse for the development and the maintenance of this shrinkage is unclear.
Aim of the study was to assess whether short-term pain relief induces changes in the cortical representation of the affected hand in patients with CRPS type I.
Case series analysis of prospectively collected data.
We enrolled a case series of 5 consecutive patients with CRPS type I (disease duration 3 – 36 months) of the non-dominant upper-limb and previously diagnosed sympathetically maintained pain (SMP) by reduction of the pain intensity of more than > 30% after prior diagnostic sympathetic block. We performed fMRI for analysis of the cortical representation of the affected hand immediately before as well as one hour after isolated sympathetic block of the stellate ganglion on the affected side.
Wilcoxon-Test, paired t-test, P < 0.05.
Pain decrease after isolated sympathetic block (pain intensity on the numerical rating scale (0 – 10) before block: 6.8 ± 1.9, afterwards: 3.8 ± 1.3) was accompanied by an increase in the blood oxygenation level dependent (BOLD) response of cortical representational maps only of the affected hand which had been reduced before the block, despite the fact that clinical and neurophysiological assessment revealed no changes in the sensorimotor function.
The interpretation of the present results is partly limited due to the small number of included patients and the missing control group with placebo injection.
The association between recovery of the cortical representation and pain relief supports the hypothesis that pain could be a relevant factor for changes of somatosensory cortical maps in CRPS, and that these are rapidly reversible

RS – we are either in pain or not in pain. If our focus is elsewhere and we are not experiencing pain, then we are not in pain. Whilst this may sound obvious, many people tell me that they are in pain all of the time. When I ask about times that they feel no pain, an oft given answer is that the pain is hidden at times when they do not feel it. Pain cannot hide. It is on-off, binary. At any given moment, we are either in pain or not in pain. Every moment changes and hence pain can change in a moment — referring to the rapidly reversible change in maps in this article; and why wouldn’t we have the ability to rapidly adapt? I believe we can change and it happens in a moment — our thinking, actions and experiences. Consider how we can be happy in a moment, and sad in a moment. Happiness is a feeling, pain is a feeling. Both have a purpose, to motivate us to do something or think in a particular way. There is a desperate need to change the globe’s thinking on pain, this being my main purpose. In doing so, we can alleviate a vast amount of suffering from pain, narrowing it down the pain that we need for survival and eliminating the pain that persists for no good reason.

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