Beyond Acute Analgesia: Perioperative Transcutaneous Auricular Vagus Nerve Stimulation for Postoperative Pain Chronification and Recovery Trajectories: A Systematic Review of Randomized Controlled Trials
DOI: Pending DOI
Synopsis
Background: Existing perioperative transcutaneous auricular vagus nerve stimulation (taVNS) reviews focus primarily on acute pain and opioid outcomes.
Methods: A systematic review of randomized controlled trials evaluating perioperative taVNS in adult surgical patients was conducted.
Results: Thirteen randomized controlled trials involving approximately 1,397 participants met eligibility criteria. Reported outcomes included postoperative pain, opioid consumption, rebound pain, chronic postsurgical pain, inflammatory biomarkers, sleep quality, anxiety, and recovery-related outcomes.
Conclusions: The identified literature extends beyond acute analgesia and supports investigation of taVNS as a potential modifier of postoperative pain chronification and recovery trajectories.
Background
Postoperative pain remains one of the most prevalent and undertreated perioperative complications. It contributes to prolonged opioid exposure, delayed functional recovery, and transition to chronic postsurgical pain (CPSP), which develops in 10–50% of patients. Pain chronification is increasingly understood as a dynamic process involving peripheral and central sensitisation, spinal dorsal horn neuroplasticity, rebound pain, neuroinflammation, and maladaptive recovery trajectories. Rebound pain, the acute nociceptive surge following peripheral nerve block offset, is a clinically important contributor to this transition. Interleukin-6 (IL-6) mediated neuroinflammation represents a plausible biologic mechanism linking acute postoperative pain to persistent pain states.
Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that engages descending antinociceptive pathways and modulates inflammatory signaling through the cholinergic anti-inflammatory reflex. This mechanistic profile positions taVNS as a uniquely attractive perioperative intervention capable of acting across multiple nodes of the acute-to-chronic pain transition.
Existing perioperative syntheses have focused primarily on acute pain intensity and opioid-related outcomes. We sought to characterize the randomized evidence evaluating perioperative taVNS across the postoperative pain continuum, including rebound pain, CPSP, and broader recovery trajectories.
Methods
A systematic review and meta-analysis was prospectively registered in PROSPERO 2026 (CRD420261406574). PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched without language restrictions, from inception through to May 2026. MeSH and free-text terms combining 'transcutaneous auricular vagus nerve stimulation,' 'taVNS,' 'auricular vagus nerve,' 'perioperative,' and 'postoperative pain.' was used. Eligible studies were randomized controlled trials evaluating perioperative taVNS or equivalent non-invasive auricular vagal stimulation in adults undergoing surgery. Comparators included sham stimulation, placebo stimulation, earlobe stimulation, or standard perioperative care. The primary outcome was postoperative pain intensity during the predefined subacute postoperative period (25–72 hours after surgery). Secondary outcomes included opioid consumption, rebound pain, CPSP, inflammatory biomarkers, sleep quality, recovery quality, psychosocial outcomes, postoperative nausea and vomiting, and adverse events.
Results
Database searches identified 281 records. Following duplicate removal, 192 records underwent screening. Thirteen randomized controlled trials involving approximately 1,397 participants met eligibility criteria. Included studies were published between 2022 and 2026 and evaluated orthopedic, thoracic, cardiac, endocrine, gynecologic, abdominal, colorectal, ophthalmologic, obstetric, and other surgical populations. Considerable heterogeneity was observed in stimulation protocols, timing of intervention, and comparator selection.
Acute postoperative pain was the most frequently reported outcome. However, the literature extended beyond conventional analgesic endpoints and included randomized evidence evaluating opioid consumption, rebound pain, chronic postsurgical pain (CPSP), IL-6-mediated inflammatory responses, sleep quality, anxiety, postoperative nausea and vomiting, patient-controlled analgesia utilization, and recovery-related outcomes. Two trials evaluated rebound pain, two evaluated CPSP at ≥3 months, and two evaluated IL-6-mediated inflammatory pathways. Quantitative synthesis is ongoing.
Figure 1 summarizes the postoperative pain chronification framework represented across the identified literature, including acute pain, rebound pain, neuroinflammatory pathways, chronic postsurgical pain, and recovery-related outcomes.
Discussion
The randomized evidence identified in this review supports a broader conceptualization of perioperative transcutaneous auricular vagus nerve stimulation (taVNS) than acute analgesia alone. Studies evaluating rebound pain, chronic postsurgical pain (CPSP), IL-6-mediated neuroinflammation, sleep quality, anxiety, and recovery-related outcomes suggest that taVNS may influence the transition from acute postoperative pain to persistent pain states while simultaneously affecting recovery trajectories (Figure 1). Ongoing quantitative synthesis will further define the magnitude and consistency of these effects across the postoperative continuum.
Disclosures
Nothing to disclose by any authors.
No commercial funding, industry sponsorship, consulting relationships, equity interests, or other financial conflicts of interest are related to this work. This review was conducted independently by the authors without external funding.
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