1. 2025;28;E481-E507Effectiveness of Peripheral Nerve Stimulation in Managing Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials
   Systematic Review
   Laxmaiah Manchikanti, MD, Massab Bashir Khaira, MS, Amol Soin, MD, Alan D. Kaye, MD, PhD, Nebojsa Nick Knezevic, MD, PhD, Alaa Abd-Elsayed, MD, Mahendra Sanapati, MD, Vivekanand A. Manocha, MD, and Joshua A. Hirsch, MD.

BACKGROUND: Peripheral nerve stimulation (PNS) has been used for over 50 years to treat chronic pain. Since 2015, the Food and Drug Administration (FDA) has approved percutaneously implanted PNS leads and neurostimulators, offering a minimally invasive, non-opioid alternative for managing persistent and refractory chronic pain.

OBJECTIVE: To evaluate the current evidence on PNS through a systematic review and meta-analysis.

STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs) on PNS for chronic pain management, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

METHODS: Quality was assessed using Cochrane review criteria for risk of bias and the Interventional Pain Management Techniques – Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) for randomized therapeutic trials.

A comprehensive literature search was conducted across multiple databases (1966-February 2025), supplemented by manual searches of bibliographies from relevant review articles. Included studies underwent quality assessment, best evidence synthesis, and grading using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Evidence levels were classified from Level I to Level V.

OUTCOME MEASURES: The primary outcome was the proportion of patients achieving significant pain relief and functional improvement (>= 50%) sustained for at least 12 months.

RESULTS: The present investigation identified 7 high-quality and 2 moderate-quality RCTs based on Cochrane criteria and 9 moderate-quality trials based on IPM-QRB criteria. Utilizing GRADE criteria, 7 of 9 studies demonstrated moderate evidence and clinical applicability, and 2 of 9 showed low evidence and applicability.

Overall, the combined qualitative and quantitative analysis supported a fair (Level III) evidence level, with moderate certainty and moderate strength of recommendation for:
Implantable PNS systems following a trial or selective lumbar medial branch stimulation without a trial
Temporary PNS therapy for 60 days

LIMITATIONS: A key limitation remains the scarcity of high-quality studies.

CONCLUSION: The evidence supports a fair (Level III) level of evidence with moderate certainty and recommendation strength, based on qualitative and quantitative analyses and GRADE assessment.

KEY WORDS: Chronic pain, interventional techniques, peripheral neuropathy, peripheral neuropathic pain, peripheral nerve stimulation, selective lumbar medial branch stimulation