Advances in Interventional Therapies for Painful Diabetic Neuropathy

A Systematic Review

Li Xu, MD, PhD; Zhuo Sun, MD; Elizabeth Casserly, PharmD; Christian Nasr, MD; Jianguo Cheng, MD, PhD; Jijun Xu, MD, PhD


Anesth Analg. 2022;134(6):1215-1228. 

In This Article


This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) of individual participant data.[22]

Search Strategy

Electronic databases PubMed, Scopus, Google Scholar, and Cochrane Library were searched using the following terms: "painful diabetic neuropathy" AND "randomized blinded controlled trial" OR "pilot study" OR "retrospective study" OR "systematic review" OR "meta-analysis" OR "spinal cord stimulation" OR "acupuncture" OR "botulinum toxin" OR "surgical decompression". There was no date limitation for the literature search, and the last search was conducted on April 1, 2021.

Study Selection

Inclusion criteria were meta-analyses, prospective randomized controlled trials, prospective pilot studies, retrospective reports, case reports, and case series that evaluated interventional therapies in patients with PDN. Primary outcome of interest was numerical rating or visual analog pain scales. We excluded animal studies and trials that lack adequate study description. Additional literatures were further identified after reading the full text of the relevant reports. Four of the authors (L.X., J.X., Z.S., and E.C.) independently performed the search and extracted data from articles. Any disagreements were resolved by discussion (L.X., J.X., and J.C.).

Risk of Bias Assessment and Data Synthesis

Using the Cochrane risk-of-bias tool (RoB 2),[23] risk of bias of each randomized trial was assessed by one author (J.X.) and checked by a second author (J.C.). The risk domains included the randomization process, deviation from the intended interventions, missing outcome data, measurement of the outcomes, selection of the reported results, and the overall risk of bias. All domains were assessed as "low risk of bias," "some concerns," or "high risk of bias."[23] Data synthesis was based on assessments of the quality of individual studies, outcomes assessment, and qualitative analysis. The quality of each individual article included in this analysis was assessed by applying the Cochrane review criteria[24] and the Interventional Pain Management Techniques – Quality Appraisal of Reliability and Risk of Bias Assessment (IPM – QRB) for randomized trial.[25]

Analysis of Evidence

The levels of clinical evidence and implications for recommendations of all of the included studies were graded according to "Grading Strength of Recommendations and Quality of Evidence in Clinical Guidelines" by Guyatt et al,[26] which has been cited by more than 1300 reports[27,28] (Table 1).