Cite as: Nanda M, Rayaz H, Grzybowski J. Literature review - November 2025. ASRA Pain Medicine News 2025;50. https://doi.org/10.52211/asra110125.018.

Literature Review

Acute Pain

The Association of Preoperative Opioid Use with Postdischarge Outcomes: A Cohort Study of the Michigan Surgical Quality Collaborative

Frangakis SG et al. Ann Surg 2025;282(2):234-41. https://doi.org/10.1097/SLA.0000000000006265

Summary by Monika Nanda, MBBS, MPH, FASA

Introduction: Preoperative opioid use remains a significant clinical and public health concern, with nearly one-third of surgical patients reporting opioid exposure prior to surgery. Although previous research has suggested an association between opioid use and adverse surgical outcomes, patient-reported experiences, such as pain intensity, satisfaction, and quality of life remain less understood. This study addresses these knowledge gaps using a large, statewide dataset.

Methods: This retrospective cohort study linked data from the Michigan Surgical Quality Collaborative, a registry spanning 70 hospitals, with the state’s prescription drug monitoring program. Patients undergoing nine general and gynecologic surgical procedures from 2017 to 2019 were categorized into four groups based on preoperative opioid exposure: opioid-naïve, minimal, intermittent, and chronic. The primary outcome was patient-reported postoperative pain intensity at 30 days. Secondary outcomes included emergency department visits, readmissions, reoperations, satisfaction, regret, and quality of life. Multilevel logistic regression models adjusted for demographic, clinical, and procedural variables.

Results: Among 24,888 patients, 73% were opioid-naïve, 14% had minimal, 10% intermittent, and 3% chronic opioid exposure. Compared with opioid-naïve patients, opioid-exposed patients reported higher rates of moderate (43.5% vs 39.3%) and severe pain (13.0% vs 10.0%) at 30 days. Greater opioid exposure correlated with worse outcomes across satisfaction, quality of life, and clinical events. Patients with intermittent and chronic use had significantly higher risks of emergency department visits (aOR 1.69 and 1.65, respectively) and readmissions (aOR 1.34 and 2.13, respectively).

Key Point: Preoperative opioid use is a modifiable risk factor associated with worse pain, patient-reported, and clinical outcomes after surgery.

Analgesic Efficacy of Different Volumes in Erector Spinae Plane Block in Patients Undergoing Single-Level Lumbar Spine Fixation: A Non-Inferiority Randomized Trial

Algyar MF et al. BMC Anesthesiol 2025;25(1):439.. https://doi.org/10.1186/s12871-025-03247-z

Summary by Hassan Rayaz, MD

Introduction: Spine surgery is growing rapidly, and pain management can be challenging. The erector spinae plane block (ESPB) is often used to help decrease perioperative opioid use. There have been limited studies on lower local anesthetic volume (10-15 ml) ESPBs. This study aims to determine whether lower-volume ESPBs are noninferior to higher-volume 20 ml ESPBs.

Methods: This is a randomized, double-blinded study that recruited 60 patients undergoing single level lumbar spine fixation. Twenty patients were randomized into each of the three bupivacaine 0.25% groups: 10 ml, 15 ml, and 20 ml. Patients then underwent general anesthesia with fentanyl 1 mcg/kg IV for induction and additional fentanyl boluses for increased heart rate and/or mean arterial blood pressure 20% above baseline. The same surgical team performed each surgery. After extubation, pain was assessed with the Numeric Rating Scale upon arrival to the post-anesthesia care unit, 1, 2, 4 ,6, 8, 12, 18, 24, 36, and 48 hours postoperatively. Patients were given 1 g of paracetamol IV every 8 hours and rescue analgesia (morphine 3 mg IV) for NRS>4.

Results: The primary outcome was the total morphine consumption during the initial 24 hours after surgery. There was not statistically significant difference between the different groups in the primary outcome. The secondary outcomes included postoperative pain scores, timing of first rescue analgesia, side effects/complications, and patient satisfaction. There were no statistically significant differences for the secondary outcomes either.

Key Point: Lower volume (10 or 15 ml) ESPBs are non-inferior to higher volume (20 ml) ESPBs for single-level lumbar spine fixation.

Pericapsular Nerve Group (PENG) Block Compared to Intrathecal Morphine for Analgesic Efficacy in Total Hip Arthroplasty: A Placebo-Controlled Randomized Double-Blind Non-Inferiority Trial

Oremus et al. J Clin Anesth 2025;106:111921. https://doi.org/10.1016/j.jclinane.2025.111921

Summary by Jeffrey Grzybowski, MD

Introduction: Total hip arthroplasty (THA) is one of the most common elective orthopedic procedures. Intrathecal (IT) morphine aims to reduce postoperative systemic opioid consumption; however, side effects of nausea, vomiting, and pruritus may adversely affect early recovery. The Pericapsular Nerve Group (PENG) block is hypothesized to provide non-inferior analgesia after THA compared to IT morphine, while preserving motor function.

Methods: Adults undergoing unilateral THA received spinal anesthesia (15 mg isobaric 0.5% levobupivacaine). Subsequently, patients received randomized therapies: either 100 mcg IT morphine + placebo PENG block (20 mL saline) or IT saline placebo + PENG block with 20 mL of 0.5% levobupivacaine and 2 mg dexamethasone. Oral postoperative multimodal agents were standardized. Patients experiencing breakthrough pain received 4 mg intravenous morphine boluses. Pain at rest and during hip flexion were assessed through 48 hours post-surgery. Rescue morphine doses and straight leg raise test results were recorded. Non-inferiority margins for PENG-IT morphine differences were 0.75 NRS points for pain scores and 10 for cumulative milligram morphine equivalents (MME).

Results: Sixty patients were randomized, and 30 patients in each treatment group were analyzed. Non-parametric Analysis of covariance (ANCOVA) demonstrated non-inferiority of PENG block vs IT morphine for maximum rest pain at 48 hours: difference (95% CI) of 0.278 (-0.083, 0.639), and maximum pain in hip flexion at 48 hours: difference of -0.185 (-0.713, 0.343). The difference in cumulative MME over 48 hours was -2.1 (-6.5, 1.9) between PENG and IT morphine. Straight leg raise test failure rates were similar in the two groups.

Key Point: Compared to IT morphine, PENG block provides non-inferior analgesia after THA under spinal without compromise of motor function.

Chronic Pain

Minimally Invasive Lumbar Decompression (MILD) in Patients with Lumbar Spinal Stenosis: A Systematic Review of Randomized and Prospective Trials

Orhurhu V, Brancolini S, Zheng D, et al. J Pain Res 2025;18:3527-40. https://doi.org/10.2147/JPR.S521038

Summary by Mamta Chura, MD

Introduction: Lumbar spinal stenosis (LSS) is a leading cause of pain, disability, and spinal surgery in older adults. Conservative options often provide only temporary relief, while open decompression carries higher complication risks. Minimally invasive lumbar decompression (MILD) has emerged as a less morbid alternative; yet the strength of supporting evidence needs systematic evaluation.

Methods: The purpose of this study was to evaluate the evidence on the MILD procedure for chronic pain patients with LSS. Following PRISMA guidelines, investigators systematically reviewed randomized and prospective trials published from 2000–2023 assessing MILD for LSS with neurogenic claudication due to hypertrophied ligamentum flavum. The primary outcome was pain (VAS/NRS) and secondary outcome was function (Oswestry Disability Index). Methodologic rigor was assessed using Cochrane methodology, GRADE, and interventional pain management–specific risk-of-bias tools.

Results: Fifteen prospective studies (7 RCTs, 8 prospective trials) met inclusion criteria. The median follow-up was 1 year (range of 6 weeks to 2 years). Nine of 14 studies (64.3%) demonstrated statistically and clinically significant improvements in pain (≥3-point NRS decrease) at study endpoint. Eleven of 13 studies (84.6%) that used ODI met criteria for a clinically significant change. Safety outcomes were favorable for MILD; serious adverse events were rare and included isolated cases of deep venous thrombosis, pulmonary embolism, hernia, and transient postoperative pain.

Key Point: MILD is supported by high-quality evidence as an effective, durable, and safe alternative to open decompression for lumbar spinal stenosis, providing sustained improvements in pain and function with minimal morbidity.

Melatonin for Neuropathic Pain: A Double-Blind, Placebo-Controlled, Randomized, Crossover Trial

Gilron I, Elkerdawy H, Tu D, et al. Pain 2025;166(11):2541-9. https://doi.org/10.1097/j.pain.0000000000003651

Summary by Vandana Sharma, MD, FASA

Introduction: Sleep disturbance is commonly associated with neuropathic pain (NP). Some evidence suggests that melatonin, a pineal hormone associated with sleep and circadian rhythms, may reduce pain in clinical settings. This is a clinical trial evaluating the analgesic efficacy of melatonin for treating NP.

Methods: The study used a double-blind, placebo-controlled, randomized crossover design involving 31 participants with chronic NP. Participants were randomized into crossover sequences with melatonin (up to 12 mg/day) and placebo in two 4-week treatment periods, separated by a 1-week washout. Pain intensity and other outcomes were assessed weekly. The primary outcome was the mean daily average pain intensity experienced while on the maximally tolerated dose (MTD) of melatonin or placebo during the final week. Secondary outcomes were adverse events and measures of sleep, mood, and quality of life.

Results: Thirty participants completed both treatment periods and were included in trial analyses. The mean maximal tolerated dose of melatonin was 11.9 mg/day. There was no statistically significant difference in average daily pain intensity (standard error) between melatonin 4.1(0.3) and placebo 4.2(0.3) at the MTD (P=0.8). No significant differences were observed in secondary outcomes for sleep or quality of life. Melatonin was well-tolerated in both groups, with mild side effects like headache and drowsiness.

Key Point: The trial found no evidence to support the use of melatonin as an effective treatment for neuropathic pain. While melatonin was safe and well-tolerated, it did not outperform placebo in reducing pain or improving secondary outcomes.

Surgery Versus Corticosteroid Injection For Carpal Tunnel Syndrome (DISTRICTS): An Open-Label, Multicentre, Randomised Controlled Trial

Palmbergen WAC et al. Lancet 2025;405(10495):2153-63. https://doi.org/10.1016/S0140-6736(25)00368-X

Summary by Vinita Singh, MD, MSCR

Introduction: Treatment options for carpal tunnel syndrome (CTS) include steroid injection around the median nerve in the wrist and surgical decompression by releasing the transverse carpal ligament. Prior studies have demonstrated the short-term benefit of corticosteroid injections but questioned their durability compared with surgery. A large, pragmatic, clinical trial comparing surgery-first with injection injection-first strategy for CTS was conducted.

Methods: This study was a multicenter, open-label, randomized controlled trial across 31 hospitals in the Netherlands. A total of 934 adults with electrophysiologically or sonographically confirmed CTS were randomized 1:1 to carpal tunnel release surgery versus steroid injection. Patients were stratified by laterality of symptoms, presence of concomitant disease as a risk factor for CTS, and history of prior ipsilateral CTS injection. The primary outcome was recovery at 18 months, defined as a six-item carpal tunnel symptom severity score <8. Secondary outcomes included additional recovery-related questions and adverse events. Patients were allowed to crossover and receive additional treatments as clinically indicated.

Results: The surgery-first group had higher recovery (61%) compared with injection-first (45%); with relative risk of 1.36 (95% CI 1.19–1.56; p<0.0001) in favor of surgery. The incidence of adverse events reported in the two groups were similar except for more wound or skin problems requiring treatment in the surgery group and more reports of changed sensation in the hand in the injection group. Many patients (49%) in the injection-first group eventually underwent surgery.

Key Point: This trial demonstrated that surgery as initial treatment yielded significantly higher recovery rates at 18 months compared with an injection-first approach.