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. 2023 Jun 12;6(6):CD009416.
doi: 10.1002/14651858.CD009416.pub3.

Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews

Michael C Ferraro  1   2 , Aidan G Cashin  1   2 , Benedict M Wand  3 , Keith M Smart  4   5 , Carolyn Berryman  6   7 , Louise Marston  8 , G Lorimer Moseley  6 , James H McAuley  1   2 , Neil E O'Connell  9
Affiliations

Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews

Michael C Ferraro et al. Cochrane Database Syst Rev. .

Abstract

Background: Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013.

Objectives: To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS.

Methods: We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria. Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment. MAIN RESULTS: We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison. There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence interval (CI) -1.8 to -3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate-certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181). There was moderate-certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison. There was low-certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N-acetylcysteine, but no effect size was reported. There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported. For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low- and very low-certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids.

Authors' conclusions: Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult. Current non-Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.

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Conflict of interest statement

NOC and BMW were authors of one included review (O'Connell 2016) and KMS, MCF, BM and NOC were authors of another included review (Smart 2022). Different authors (AGC, CB) conducted the AMSTAR 2 assessments for these reviews.

GLM was the lead author on three included studies (Moseley 2004; Moseley 2006; Moseley 2009) but was not involved in the data extraction process or writing of or interpretation of results for these trials. GLM has co‐authored a textbook on the use of graded motor imagery in chronic pain, for which he receives author royalties.

MCF, AGC, BMW, GLM, JHM and NOC are involved in the conduct of a randomised controlled trial testing memantine and graded motor imagery for complex regional pain syndrome. At the time of writing this review, the trial is recruiting participants and is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12621000175875).

CB has an annual contract (Independent Contractor) to provide 12 hours of pain education lectures to pain and spine fellows at Kaiser Permanente. This position is not relevant nor a conflict to this title.

NOC is an author and PaPaS Co‐ordinating editor. NOC had no input into the editorial decisions or processes for this overview.

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