Daily Anesthesiology Research Analysis
Analyzed 101 papers and selected 3 impactful papers.
Summary
Three impactful studies in anesthesiology highlight neuromodulation and stewardship. A mechanistic Nature Communications study maps an auricle-to-brain analgesic circuit for taVNS, a factorial RCT shows taVNS reduces chronic postsurgical pain after OPCABG, and a population study in Anesthesiology identifies large, institution-driven variation in extended-release opioid dispensing after arthroplasty with protective associations for neuraxial and regional anesthesia.
Research Themes
- Neuromodulation for perioperative and chronic pain
- Opioid stewardship and discharge prescribing after arthroplasty
- Mechanistic mapping of vagal analgesia circuits
Selected Articles
1. Auricular vagus nerve stimulation drives analgesia via an auricle-brain axis in a mouse model of neuropathic pain.
In mice, taVNS applied to the auricular concha activates a defined JNG→NTS (POMC)→vlPAG circuit to produce analgesia. Optogenetic activation at multiple nodes recapitulates the effect, while chemogenetic silencing abolishes it, establishing a mechanistic substrate for taVNS-driven pain relief.
Impact: This study provides first-in-class circuit-level evidence for how taVNS drives analgesia, a key step toward rational parameter optimization and indication targeting. It bridges peripheral auricular input to central pain-modulating structures.
Clinical Implications: While preclinical, these findings support translational trials of taVNS for perioperative and chronic pain, inform electrode placement and dosing paradigms, and suggest biomarkers (e.g., brainstem-PAG engagement) to guide responder selection.
Key Findings
- taVNS of the auricular concha induces robust analgesia in a neuropathic pain mouse model.
- An auricle-to-brain circuit JNG→NTS (pro-opiomelanocortinergic neurons)→vlPAG mediates the effect.
- Optogenetic activation of central vagus terminals, JNG fibers, or NTS→vlPAG neurons mimics taVNS analgesia; chemogenetic silencing at these nodes abolishes it.
Methodological Strengths
- Multimodal mechanistic approach (viral tracing, in vivo calcium imaging, multi-electrode recordings, opto/chemogenetics).
- Convergent causal manipulations across multiple nodes of the identified circuit.
Limitations
- Findings are in mice; human generalizability and optimal stimulation parameters remain to be established.
- No direct behavioral or physiological biomarkers for clinical responder stratification were tested.
Future Directions: Early-phase human studies should test taVNS parameter sets guided by this circuit, develop imaging/EEG biomarkers of NTS–PAG engagement, and evaluate analgesic efficacy in perioperative and chronic neuropathic pain populations.
Despite its long-recognized effects in relieving pain, the neural substrates of auricular stimulation remain elusive. Here, we show that trans-auricular vagus nerve stimulation (taVNS), i.e., electrical stimulation of the auricular concha, effectively induces analgesia in a mouse model of neuropathic pain. Viral tracing, microendoscopic calcium imaging, and multi-electrode recordings reveal that auricular vagal signals travel to the jugular-nodose ganglia (JNG), which in turn connect to pro-opiomelanocortinergic neurons in nucleus tractus solitarius (NTS), subsequently activating glutamatergic neurons in ventrolateral periaqueductal gray (vlPAG). Optogenetic stimulation of central vagus terminals, JNG-derived auricular peripheral fibers, or vlPAG-projecting NTS neurons mimics taVNS-induced analgesia, whereas chemogenetic silencing of central vagus terminals or NTS neurons abolishes this effect. This study identifies an auricle-to-brain circuit underlying taVNS-driven analgesia in mice, with potential for facilitating taVNS optimization for pain management and other neurological conditions.
2. Transcutaneous Auricular Vagus Nerve Stimulation and Pectoral-Intercostal Fascial Block for the Prevention of Chronic Postsurgical Pain in Elderly Patients Undergoing Off-Pump Coronary Artery Bypass Grafting: A 2×2 Factorial, Double-Blinded, Randomized Clinical Trial.
In a double-blind 2×2 factorial RCT (n=260, ≥60 years) undergoing OPCABG, taVNS reduced 3‑month CPSP (28.6% vs 40.9% vs sham), with no taVNS×PIFB interaction; single-shot PIFB had limited preventive effect. Mediation suggested benefits were partly through reductions in acute pain and inflammation.
Impact: This is the first adequately powered factorial RCT demonstrating perioperative taVNS prevents CPSP in a high-risk cardiac population, positioning neuromodulation as a scalable, opioid-sparing preventive strategy.
Clinical Implications: Consider taVNS as an adjunct in enhanced recovery pathways for elderly OPCABG patients to reduce CPSP risk; routine single-shot PIFB alone may be insufficient for CPSP prevention.
Key Findings
- taVNS reduced 3‑month CPSP compared with sham (28.6% vs 40.9%).
- No interaction between taVNS and PIFB; single-shot PIFB provided limited preventive effect.
- Mediation analyses indicate benefits partially mediated by reduced acute pain and inflammation.
Methodological Strengths
- Double-blinded, randomized 2×2 factorial design with 260 elderly OPCABG patients.
- Prespecified multivariable modeling and mediation analysis to explore mechanisms.
Limitations
- Single-center trial; generalizability beyond elderly OPCABG patients is uncertain.
- Follow-up at 3 months for the primary endpoint; longer-term CPSP outcomes are needed.
Future Directions: Replicate in multicenter settings, optimize taVNS parameters, extend follow-up, and assess integration with multimodal analgesia to prevent CPSP across procedures.
BACKGROUND: Chronic postsurgical pain (CPSP) is common after off-pump coronary artery bypass grafting (OPCABG) in elderly patients. This trial investigated the efficacy of perioperative transcutaneous auricular vagus nerve stimulation (taVNS) and pectoral-intercostal fascial block (PIFB) for CPSP prevention. METHODS: In this 2×2 factorial trial, 260 elderly patients (≥60 years) undergoing OPCABG were randomized to taVNS + ropivacaine PIFB, taVNS + placebo PIFB, sham taVNS + ropivacaine PIFB, or sham taVNS + placebo PIFB groups. The primary outcome was CPSP incidence at 3 months postoperatively. Several secondary outcomes were evaluated. Logistic regression was employed to analyze risk factors associated with CPSP. Lastly, mediation analyses were performed to explore the mediating factors between interventions and CPSP. RESULTS: The overall incidence of CPSP was 34.6%. No interaction was found between taVNS and PIFB. Compared with sham taVNS, taVNS significantly reduced CPSP incidence (28.6% vs 40.9%, CONCLUSION: Perioperative taVNS significantly reduced CPSP incidence and enhanced postoperative recovery in elderly OPCABG patients, partly mediated by alleviating acute pain and inflammation. Single-shot PIFB showed limited preventive effect on overall CPSP.
3. A population-based cross-sectional analysis of extended-release opioid dispensing incidence, prognostic factors, and variation after total joint arthroplasty.
In 229,995 hip/knee arthroplasties, 12.1% of patients filled new extended‑release opioid prescriptions within 7 days. Neuraxial anesthesia, peripheral nerve blocks, and acute pain service involvement were associated with reduced dispensing, while substantial variation was driven by hospitals and surgeons rather than patients.
Impact: Defines modifiable system-level levers to curb inappropriate ER opioid exposure post-arthroplasty and quantifies protective effects of anesthetic/regional strategies at scale.
Clinical Implications: Implement institutional stewardship with standardized discharge analgesia protocols; preferentially use neuraxial anesthesia and regional blocks and engage acute pain services to reduce ER opioid dispensing.
Key Findings
- 12.1% (27,915/229,995) filled new ER opioid prescriptions within 7 days post-discharge.
- Neuraxial anesthesia (OR 0.79), peripheral nerve block (OR 0.84), and acute pain service (OR 0.77) showed protective associations.
- Variation was large across hospitals (VPC 46%, MOR 9.3) and surgeons (VPC 26%, MOR 5.3), with minimal anesthetist-level variation.
Methodological Strengths
- Population-based analysis with very large sample and multilevel modeling capturing institution- and clinician-level effects.
- Comprehensive inclusion of patient, surgical, anesthetic, and hospital covariates.
Limitations
- Observational cross-sectional design limits causal inference; dispensing does not equal consumption.
- Findings from a single health system (Ontario) may limit external generalizability.
Future Directions: Test stewardship interventions (e.g., standardized discharge order sets) in cluster RCTs; evaluate patient-centered outcomes and actual opioid consumption.
INTRODUCTION: Extended-release opioids (EROs) are not recommended for acute postoperative pain, yet their prescribing persists. This study examined the incidence, predictors, and variation in ERO dispensing after total hip and knee arthroplasty. METHODS: We conducted a population-based cross-sectional study of adults undergoing primary total hip or knee arthroplasty between 2013 and 2022 using linked administrative databases in Ontario, Canada. The primary outcome was fulfillment of an ERO prescription within seven days of discharge. Multilevel logistic regression estimated associations between patient, surgical, anesthetic, and hospital factors and filling an ERO prescription. Variation was quantified using variance partition coefficients (VPCs) and median odds ratios (MOR) with 95% confidence intervals (CI), based on random effects. RESULTS: Among 229,995 knee and hip arthroplasty procedures, 27,915 (12.1%) patients filled a new ERO prescription post-discharge. Male sex (OR 1.14, 95% CI 1.09-1.19), preoperative opioid exposure (Opioid Naïve-Exposed-Tolerant (ONET) Score 2 OR 1.21, 95% CI 1.15-1.27; ONET 3 OR 1.38, 95% CI 1.20-1.58), and ASA 3 status (OR 1.07, 95% CI 1.01-1.12) increased odds of filling a new ERO prescription. Neuraxial anesthesia (OR 0.79, 95% CI 0.74-0.84), peripheral nerve block (OR 0.84, 95% CI 0.79-0.89), and acute pain service involvement (OR 0.77, 95% CI 0.70-0.85) were protective against filling a new ERO prescription. Substantial variation was found across hospitals (VPC 46%, 95% CI 0.4-0.54; MOR 9.3, 95% CI 6.57-15.27) and surgeons (VPC 26%, 95% CI 0.24-0.26; MOR 5.3, 95% CI 4.63-6.11), with minimal anesthetist-level variation (VPC 1%, 95% CI 0.010-0.011; MOR 1.4, 95% CI 1.36-1.46). Patient-level factors explained a minority of variation. CONCLUSIONS: One in ten patients fills an ERO prescription after total hip or knee arthroplasty, a practice with high variation that is predominantly driven by institutional and surgical practice patterns rather than patient factors. Future research should explore institutional stewardship, standardized discharge protocols, and multidisciplinary engagement to reduce unnecessary postoperative exposure to EROs.