In reply: Pain exposure physical therapy in complex regional pain syndrome: promising enough to warrant further investigation

  • Daniela Bravo
  • Silvia Duong
  • Keith J. Todd
  • Roderick J. Finlayson
  • D. Q. TranEmail author
In reply

To the Editor,

We thank Dr. Staal et al.1 for their interest in our review article2 on complex regional pain syndrome (CRPS) and for bringing to our attention a trial that had escaped the literature search.3

We have read the three trials3-5 discussed by Staal et al.1 and would like to present readers with a more cautious interpretation. First, in Barnhoon et al.’s study, an intention-to-treat analysis clearly showed no benefit associated with pain exposure physical therapy (PEPT) compared with conventional treatment.4 Staal et al.1 argue that more “nuanced” (i.e., positive) findings could be derived from a per protocol analysis. We respectfully disagree as the scientific gold standard remains intention-to-treat and not per protocol analysis.6 In fact, introducing the latter confers inherent bias (rather than “nuance”), particularly as the authors might not have conducted a per protocol analysis had the intention-to-treat analysis revealed a treatment effect. For example, in Barnhoon et al.’s secondary analysis of the healthcare costs incurred during the first nine months of treatment,5 the intention-to-treat analysis revealed that conventional treatment was 64% more expensive than PEPT. This led the authors to immediately conclude that cost differences favour PEPT without resorting to the “nuanced” per protocol analysis to confirm or disprove these findings. Second, den Hollander et al.2 have indeed reported that, compared with conventional treatment, exposure in vivo resulted in decreased self-reported disability, pain intensity, pain catastrophizing, perceived harmfulness of activities, and increased health-related quality of life. However, den Hollander et al.3 specifically recruited subjects with documented pain-related fear, whereas Barnhoon et al.4 did not triage for such a subset of patients. Despite this important distinction, Staal et al.1 draw a parallel between the two trials because they “share the theory of exposure to pain and stimulated use of the affected limb”. Such an argument is flawed—it would be akin to stating that, since root canal therapy is indicated for dental cavities complicated by abscesses, it should also be performed for all cavities.

In summary, based on our reading of the literature, we respectfully disagree with the assertion that PEPT “deserves a place in the treatment of CRPS”. We concede that the current evidence supports its role in patients with pain-related fear. However, the available trials do not (yet) support its use in other subsets of CRPS patients. Nonetheless, they highlight the need for further randomized investigation with proper intention-to-treat analysis.


Conflicts of interest

None declared.

Editorial responsibility

This submission was handled by Dr. Hilary P. Grocott, Editor-in-Chief, Canadian Journal of Anesthesia.


  1. 1.
    Staal JB, Klomp FP, Nijhuis-van der Sanden MW. Pain exposure physical therapy in complex regional pain syndrome: promising enough to warrant further investigation? Can J Anesth 2019; 66. DOI:
  2. 2.
    Duong S, Bravo D, Todd KJ, Finlayson RJ, Tran DQ. Treatment of complex regional pain syndrome: an updated systematic review and narrative synthesis. Can J Anesth 2018. DOI: Scholar
  3. 3.
    den Hollander M, Goossens M, de Jong J, et al. Exposure or protect? A randomized controlled trial of exposure in vivo vs pain contingent treatment as usual in patients with complex regional pain síndrome type 1. Pain 2016; 157: 2318-29.CrossRefGoogle Scholar
  4. 4.
    Barnhoorn KJ, van de Meent H, van Dongen RT, et al. Pain exposure physical therapy (PEPT) compared to conventional treatment in complex regional pain syndrome type 1: a randomised controlled trial. BMJ Open 2015; 5: e008283.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Barnhoorn K, Staal JB, van Dongen RT, et al. Pain exposure physical therapy versus conventional treatment in complex regional pain syndrome type 1-a cost-effectiveness analysis alongside a randomized controlled trial. Clin Rehabil 2018. DOI: Scholar
  6. 6.
    McCoy CE. Understanding the intention-to-treat principle in randomized controlled trials. West J Emerg Med 2017; 18: 1075-8.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Canadian Anesthesiologists' Society 2018

Authors and Affiliations

  1. 1.Department of Anesthesia, Hospital Clínico Universidad de ChileUniversity of ChileSantiagoChile
  2. 2.Jewish General Hospital, Herzl Family Medicine Center MontrealMontrealCanada
  3. 3.Department of Anesthesia, Montreal General HospitalMcGill UniversityMontrealCanada

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