Cite as: Grzybowski J, Chura M. Literature review - February 2026. ASRA Pain Medicine News 2026;51. https://doi.org/10.52211/asra020126.014.

Literature Review

Acute Pain

Opioid-Free Versus Opioid-Based Anaesthesia and Analgesia for Patients at Low Risk for Acute Postoperative Pain Undergoing Laparoscopic Surgery: A Randomized Controlled Trial

Mogianos K et al. J Clin Ane 2026;108:112058. https://doi.org/10.1016/j.jclinane.2025.112058 

Summary by Jeffrey Grzybowski, MD

Introduction: Pain associated with peripheral venous cannulation (VCP) can be used to predict the risk of acute postoperative pain (APOP). This study aimed to determine if opioid-free anesthesia (OFA) was non-inferior to the standard of care (SOC) in patients identified as low-risk for APOP.

Methods: Adult patients undergoing laparoscopic surgery (ASA < III) were differentiated into pain sensitivity cohorts. Patients with VCP < 2.0 were allocated to this low-risk cohort and subsequently randomized to either OFA or SOC. OFA was maintained with sevoflurane along with esketamine and dexmedetomidine infusions. A lidocaine bolus was given before the end of surgery. The SOC strategy included preoperative oxycodone administration and general anesthesia maintained with either propofol or sevoflurane (both with remifentanil). IV oxycodone 0.1 mg/kg was given before terminating general anesthesia. The primary outcome was the difference in the worst APOPPACU (worst pain score during the first 90 minutes in the post-anesthesia care unit (PACU)) score between groups.

Results: 154 patients were analyzed as intention-to-treat. APOPPACU was 4.8 (±3.2) for OFA and 4.6 (±3.1) for SOC (95%CI -0.8 to 1.2, P = 0.67). There was no difference in the proportion of patients with moderate to severe APOP in the PACU (66% vs 69%, P = 0.65). There were no secondary advantages for postoperative nausea and vomiting (PONV), persistent postoperative pain, or quality of recovery with OFA.

Key Point: When individualizing anesthesia based on predicted risk for APOP, OFA is non-inferior to a traditional opioid-based strategy for patients at low risk for APOP undergoing laparoscopic surgery and produces similar outcomes.

The Effect of Intraoperative Methadone During Spine Fusion Surgery on Postoperative Opioid Requirements: A Randomized Clinical Trial

Uhrbrand CG et al. Spine 2025; 50(21):1459-66. https://doi.org/10.1097/BRS.0000000000005477

Summary by James C. Krakowski, MD

Introduction: Spine fusion surgery is typically followed by substantial postoperative pain and opioid requirements. Methadone, a long-acting opioid with nasal N-methyl-D-aspartate antagonism and monoamine reuptake inhibition, may offer prolonged analgesia and opioid-sparing benefits. This randomized trial sought to determine whether intraoperative methadone, given either prior to incision or prior to closure, reduces postoperative opioid requirements compared with morphine.

Methods: This single-center, double-blind, randomized controlled trial included adult patients undergoing lumbar spine fusion of fewer than five levels. Patients were randomized to receive 0.2 mg/kg ideal body weight of methadone before incision (METpre), methadone before closure (METpost), or morphine before closure (MORpost). Dosing was decreased to 0.15 mg/kg for opioid-naïve patients >65 years. Intraoperative and postoperative care followed standardized, institutional protocols, including demand-only morphine, and patient-controlled analgesia initiated at extubation. The primary outcome was cumulative opioid consumption (oral morphine equivalents (OME)) at 6 and 24 hours following extubation. Secondary outcomes included pain scores, adverse events, sedation, PONV, PACU discharge time, and opioid use and pain at 3 months.

Results: 113 of 124 enrolled participants completed the trial (METpre n=38, METpost n=39, MORpost n=36). No significant differences in OME were found at 6 or 24 hours (P=0.518 and P=0.457, respectively). Pain scores were similar although METpre showed decreased pain at 48 and 72 hours. Adverse events were infrequent and comparable across groups. No differences were noted in outcomes at 3-month follow-up.

Key Point: Compared with intraoperative morphine, a single methadone dose did not decrease postoperative opioid requirements following lumbar fusion.

Comparison of Two Peripheral Regional Analgesic Techniques for Primary Elective Total Hip Arthroplasty: A Randomised Clinical Trial

Buffoli F et al. Anaesthesia 2025;80(12)1501–9 https://doi.org/10.1111/anae.16689 

Summary by Marcelle Blessing, MD

Introduction: The ideal regional anesthesia technique for primary hip arthroplasty would improve postoperative analgesia with minimal motor weakness. This study compared two motor-sparing analgesic techniques: erector spinae block (ESP) versus pericapsular nerve group (PENG) combined with lateral femoral cutaneous nerve block (LFC) in patients having elective posterolateral THA under spinal anesthesia.

Methods: This was a single-center, observer-blinded, randomized controlled trial (RCT). Patients were randomized into an anterior group (PENG+LFC) or a posterior group (ESP). The primary outcome was IV morphine use for the first 24 hours postoperatively. Secondary outcomes included pain scores, degree of sensory and motor block, incidence of complications, and incidence of chronic pain. All patients received the same multimodal analgesics.

Results: 62 patients were randomized and completed the study. For the primary outcome, there was no difference in morphine consumption in the first 24 hours after surgery between the anterior and posterior block groups (median (IQR [range]) 5 (1–10 [0–22]) mg vs. 5 (2–8.5 [0–20]) mg, respectively; p > 0.99). There was more motor block in the posterior block group (5/31 versus 1/31 patients in the anterior group); however, this was not statistically significant (p=0.09). There were no differences between the two groups in any secondary outcome.

Key Point: No differences were noted between the two groups for the primary or secondary outcomes. Either ESP or PENG with LFC was an effective regional anesthesia technique as part of a multimodal analgesic plan for primary hip replacement. 

Chronic Pain

Online Unsupervised Tai Chi Intervention for Knee Pain and Function in People with Knee Osteoarthritis: The RETREAT Randomized Clinical Trial

Zhu SJ, Hinman RS, Nelligan RK, et al. JAMA Intern Med 2026;186(1):15-25.https://doi.org/10.1001/jamainternmed.2025.5723 

Summary by Mamta Chura, MD

Introduction: Clinical guidelines endorse exercise as first-line therapy for knee osteoarthritis (OA). The RETREAT trial evaluated whether a 12-week, unsupervised, multimodal online tai chi intervention improves knee pain and physical function compared with online OA education alone.

Methods: RETREAT was a two-group, superiority, pragmatic randomized clinical trial. Adults meeting clinical criteria for knee OA (including age ≥45 years, activity-related knee pain, and minimal morning stiffness) and with walking pain ≥4/10 were randomized to (1) Control: Access to a purpose-built website with OA education and information about exercise benefits or to (2) Intervention: Access to the same OA education website plus tai chi content, a 12-week unsupervised video-based tai chi program (12 pre-recorded 45-minute videos; participants encouraged to practice ~3 times/week), and encouragement to use a supportive mobile app designed to promote adherence. Primary outcomes were change over 12 weeks in (1) knee pain during walking (NRS, 0-10) and (2) physical function difficulty (WOMAC function subscale, 0–68).

Results: Of 2,106 individuals screened, 178 were randomized (89 per group); 170 (96%) completed both primary outcomes in 12 weeks. The intervention group had significantly greater improvements than control in walking pain [control −1.3 vs tai chi −2.7; between-group mean difference −1.4 (95% CI, −2.1 to −0.7); P < .001] and function [control −6.9 vs tai chi −12.0; between-group mean difference −5.6 (95% CI, −9.0 to −2.3); P < .001]. Reported adherence among respondents averaged approximately 2.5 sessions per week.

Key Point: In adults with clinically diagnosed knee OA, a 12-week, freely accessible, unsupervised online tai chi program produced significantly greater improvements in walking pain and physical function than online education alone.

Cannabidiol Versus Placebo in Patients with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Single-Center Trial

Rasmussen MU et al. Ann Rheum Dis 2025:S0003-4967(25)04238-4. https://doi.org/10.1016/j.ard.2025.07.008

Summary by Vandana Sharma, MD, FASA

Introduction: There is an unmet need for effective treatment options for fibromyalgia. Cannabidiol (CBD) is widely used for the treatment of fibromyalgia despite insufficient evidence supporting its analgesic efficacy. The aim of this study was to evaluate the efficacy and safety of CBD in patients with fibromyalgia.

Methods: This randomized, placebo-controlled, double-blinded trial was conducted in a specialized fibromyalgia outpatient clinic in Denmark between April 2021 and April 2023. Eligible adult participants diagnosed with fibromyalgia based on American College of Rheumatology criteria were randomly assigned 1:1 to receive oral plant-based CBD 50 mg daily or placebo for 24 weeks. The primary outcome was improvement in pain intensity on the numeric rating scale (NRS), with predefined analyses of patients achieving >1-point NRS, ≥30%, and ≥50% pain reduction. Secondary outcomes were changes in sleep, activities of daily living, quality of life, and energy level.

Results: A total of 273 individuals were screened, and 200 participants were randomized. The two groups were comparable with respect to age, sex, pain duration, and severity. At the conclusion of the study, the mean change in pain was -0.4 points (95% CI: -0.82 to 0.08) in the CBD group and -1.1 points (95% CI: -1.53 to -0.63) in the placebo group. The intergroup difference of -0.7 points (95%CI -1.2 to -0.25, p=.0028) favored placebo. Adverse effects were mild and comparable between the two groups.

Key Point: CBD treatment was not effective in reducing fibromyalgia pain compared to placebo.

Implantable Peripheral Nerve Stimulation for Chronic Pain: A Systematic Review and Meta-Analysis of Analgesic Outcomes Up to 24 Months

D'Souza RS et al. Reg Anesth Pain Med 2025:rapm-2025-107160. https://doi.org/10.1136/rapm-2025-107160

Summary by Vinita Singh, MD, MSCR

Introduction: Peripheral nerve stimulators have been increasingly utilized for intractable chronic pain. This systematic review and meta-analysis evaluated the changes in pain intensity following implantable peripheral nerve stimulation (PNS) therapy for chronic pain.

Methods: A comprehensive search of multiple databases was conducted using both controlled vocabulary and free-text terms for 'peripheral nerve stimulation', 'implantable', 'neuromodulation', 'neurostimulation', and 'chronic pain'. The study included RCTs and observational studies with at least five patients. The primary outcome was the change in pain intensity from baseline to 6 months post-PNS implantation. Standardized mean differences using Hedges' g were pooled with a random-effects model to account for different pain scales. Pre-specified subgroup analyses for the 6-month primary endpoint included study design, funding source, conflicts of interest, device type, and anatomical location of stimulation.

Results: The analysis included 9,272 patients from 106 studies, including 7 RCTs, 35 prospective observational studies, and 64 retrospective observational studies. The study showed significant reductions in pain intensity from baseline through 24 months: Hedges' g = 3.08 (95% CI, 2.68 to 3.48) at 6 months and Hedges' g = 2.08 (95% CI, 1.68 to 2.48) at 24 months. The quality of GRADE evidence was rated as low due to reliance on observational studies, risk of bias, and heterogeneity. The largest effect sizes were observed for pelvic and upper-extremity pain, whereas the smallest was for truncal pain.

Key Point: Implantable PNS was associated with large, statistically significant and clinically meaningful reductions in pain intensity from baseline to all follow-up time points, with benefits sustained for up to 24 months.