#CRPS Bugle | 22nd May

Welcome to the CRPS Bugle – an update on the latest research papers and other literature that is pushing forward our understanding of the condition.

Anti tumor Necrosis Factor – Alpha Adalimumab for Complex Regional Pain Syndrome Type 1 (CRPS-I): A Case Series.

Eisenberg E, Sandler I, Treister R, Suzan E, Haddad M.

Pain Pract. 2013 May 13. doi: 10.1111/papr.12070. [Epub ahead of print]



Evidence suggests tumor necrosis factor-alpha (TNF-α) mediates, at least in part, symptoms and signs in complex regional pain syndrome (CRPS). Here, we present a case series of patients with CRPS type 1, in whom the response to the anti-TNF-α adalimumab was assessed.


Ten patients with CRPS type 1 were recruited. Assessments were performed before treatment, at 1 week, and 1, 3, and 6 months following 3 biweekly subcutaneous injections (40 mg/0.8 mL) adalimumab (Humira® ) and included the followings: Pain intensity using a 0-10 cm visual analog scale; the Short Form of the McGill Pain Questionnaire; the Beck Depression Inventory; the SF-36 questionnaire and mechanical and thermal thresholds (Von frey hair and Thermal Sensory Analyzer, respectively). In addition to the description of individual patient responses, both intention to treat (ITT) and per-protocol (PP) analyses were performed for the entire group.


Three subgroups of patients were identified (3 patients in each): “nonresponders”, “partial responders”, and “robust responders” in whom improvement in almost all parameters was noted. Both the ITT and PP analyses demonstrated only a trend toward improvement in mechanical pain thresholds following treatment (ITT χ² = 13.83, P = 0.008; PP χ² = 10.29, P = 0.036).


These results suggest adalimumab, and possibly other anti-TNF-α, can be potentially useful in some (although not in all) patients with CRPS type 1. These preliminary results along with the growing body of evidence which points to the involvement of TNF-α in the pathogenesis of CRPS justify further studies in this area.

RS – interesting findings adding to the data on targeting the imune system for CRPS. We must bear in mind that this is a case series and not an RCT. Modern thinkers in pain talk about a neuroimmune system as the two have been shown to be interactive to the point that they can be viewed as one biological system. To tackle the problem of persisting pain, we must think about and test methods that target immune activity. 


Children and adolescents with complex regional pain syndrome: More psychologically distressed than other children in pain?

Logan DE, Williams SE, Carullo VP, Claar RL, Bruehl S, Berde CB.

Pain Res Manag. 2013 Mar-Apr;18(2):87-93.


BACKGROUND: Historically, in both adult and pediatric populations, a lack of knowledge regarding complex regional pain syndrome (CRPS) and absence of clear diagnostic criteria have contributed to the view that this is a primarily psychiatric condition.

OBJECTIVE: To test the hypothesis that children with CRPS are more functionally disabled, have more pain and are more psychologically distressed than children with other pain conditions.

METHODS: A total of 101 children evaluated in a tertiary care pediatric pain clinic who met the International Association for the Study of Pain consensus diagnostic criteria for CRPS participated in the present retrospective study. Comparison groups included 103 children with abdominal pain, 291 with headache and 119 with back pain. Children and parents completed self-report questionnaires assessing disability, somatization, pain coping, depression, anxiety and school attendance.

RESULTS: Children with CRPS reported higher pain intensity and more recent onset of pain at the initial tertiary pain clinic evaluation compared with children with other chronic pain conditions. They reported greater functional disability and more somatic symptoms than children with headaches or back pain. Scores on measures of depression and anxiety were within normal limits and similar to those of children in other pain diagnostic groups.

CONCLUSIONS: As a group, clinic-referred children with CRPS may be more functionally impaired and experience more somatic symptoms compared with children with other pain conditions. However, overall psychological functioning as assessed by self-report appears to be similar to that of children with other chronic pain diagnoses. Comprehensive assessment using a biopsychosocial framework is essential to understanding and appropriately treating children with symptoms of CRPS.


Cochrane Database Syst Rev. 2012 Dec 12;12:CD003968. doi: 10.1002/14651858.CD003968.pub3.

Psychological therapies for the management of chronic and recurrent pain in children and adolescents.

Eccleston C, Palermo TM, de C Williams AC, Lewandowski A, Morley S, Fisher E, Law E.


Centre for Pain Research, The University of Bath, Bath, UK. c.eccleston@bath.ac.uk



Chronic pain affects many children, who report severe pain, distressed mood, and disability. Psychological therapies are emerging as effective interventions to treat children with chronic or recurrent pain. This update adds recently published randomised controlled trials (RCTs) to the review published in 2009.


To assess the effectiveness of psychological therapies, principally cognitive behavioural therapy and behavioural therapy, for reducing pain, disability, and improving mood in children and adolescents with recurrent, episodic, or persistent pain. We also assessed the risk of bias and methodological quality of the included studies.


Searches were undertaken of MEDLINE, EMBASE, and PsycLIT. We searched for RCTs in references of all identified studies, meta-analyses and reviews. Date of most recent search: March 2012.


RCTs with at least 10 participants in each arm post-treatment comparing psychological therapies with active treatment were eligible for inclusion (waiting list or standard medical care) for children or adolescents with episodic, recurrent or persistent pain.


All included studies were analysed and the quality of the studies recorded. All treatments were combined into one class: psychological treatments; headache and non-headache outcomes were separately analysed on three outcomes: pain, disability, and mood. Data were extracted at two time points; post-treatment (immediately or the earliest data available following end of treatment) and at follow-up (at least three months after the post-treatment assessment point, but not more than 12 months).


Eight studies were added in this update of the review, giving a total of 37 studies. The total number of participants completing treatments was 1938. Twenty-one studies addressed treatments for headache (including migraine); seven for abdominal pain; four included mixed pain conditions including headache pain, two for fibromyalgia, two for pain associated with sickle cell disease, and one for juvenile idiopathic arthritis. Analyses revealed five significant effects. Pain was found to improve for headache and non-headache groups at post-treatment, and for the headache group at follow-up. Mood significantly improved for the headache group at follow-up, although, this should be interpreted with caution as there were only two small studies entered into the analysis. Finally, disability significantly improved in the non-headache group at post-treatment. There were no other significant effects.


Psychological treatments are effective in reducing pain intensity for children and adolescents (<18 years) with headache and benefits from therapy appear to be maintained. Psychological treatments also improve pain and disability for children with non-headache pain. There is limited evidence available to estimate the effects of psychological therapies on mood for children and adolescents with headache and non-headache pain. There is also limited evidence to estimate the effects on disability in children with headache. These conclusions replicate and add to those of the previous review which found psychological therapies were effective in reducing pain intensity for children with headache and non-headache pain conditions, and these effects were maintained at follow-up.

RS – Both of these pieces of work highlight the need for a comprehensive approach that target the physical, cognitive and emotional dimensions of pain.

For further information about our CRPS clinic in London and Surrey, call us on 07932 689081 or visit our clinic site here: Specialist Pain Physio Clinics


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