Jiyoung Kim, Ji Yeong Kim, Hwa Yong Shin, Sung Eun Sim, Siwook Chung, Youngjae Jeon, Sang Hyun Kim, Jong Min Jeong, Jieun Kim, U-Young Lee, and Hue Jung Park. Korean J Pain -0001;0:. https://doi.org/10.3344/kjp.23112

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly encountered in pain practice, but reported pain improvement may reflect direct antinociception, weight loss, metabolic change, or disease-specific effects. This structured narrative review examined these possibilities and relevant safety issues. Methods: PubMed/MEDLINE, Embase, and Web of Science Core Collection were searched through 15 May 2026. Peer-reviewed human studies, key mechanistic preclinical studies, systematic reviews and meta-analyses, and professional guidance relevant to pain outcomes or procedural safety were considered. Metabolic-only and non-peer-reviewed reports were excluded, and human pain-primary evidence was prioritized. Results: Preclinical data support plausible mechanisms involving spinal microglia, interleukin-10, beta-endorphin, neuroinflammation, and sensory-neuron signaling, but direct analgesic efficacy at systemic clinical doses has not been demonstrated. In STEP 9 (n = 407), mean WOMAC pain scores at 68 weeks changed from baseline by −41.7 points with semaglutide 2.4 mg and −27.5 points with a placebo; body weight changed by −13.7% and −3.2%, respectively. Liraglutide produced additional weight loss without superior knee-pain reduction. Diabetic peripheral neuropathy evidence was mainly structural or neurophysiologic; idiopathic intracranial hypertension and ROSE-010-treated irritable bowel syndrome showed disease-specific signals, whereas fibromyalgia- and opioid-related findings remained observational or hypothesis-generating. Gastrointestinal dysmotility, reduced intake, and lean-mass loss may offset functional benefits. Conclusions: GLP-1RAs are not established analgesics. Current human signals are best interpreted as indirect metabolic–functional or disease-specific effects. Future trials should use validated pain-primary outcomes, control for weight loss, and monitor treatment-related harms.

Shoulder surgery often requires effective regional analgesia, but interscalene brachial plexus block, the current reference technique, is frequently associated with hemidiaphragmatic paresis and upper-extremity motor blockade. These limitations have driven interest in diaphragm-sparing approaches that preserve respiratory and functional recovery. The sub-omohyoid fascial plane block (SOFPB) is an emerging ultrasound-guided interfascial concept that targets the fascial compartment deep to the omohyoid muscle near the superior trunk–suprascapular nerve complex. In this narrative review, SOFPB is considered as an operational umbrella term for closely related sub-omohyoid approaches rather than as a fully standardized single technique. This review summarizes the anatomical rationale, sonoanatomy, proposed mechanisms, technical considerations, and available clinical evidence for SOFPB and related sub-omohyoid approaches in shoulder surgery. Current evidence suggests that sub-omohyoid approaches may provide clinically meaningful analgesia through suprascapular nerve involvement, partial superior trunk coverage, and variable interfascial spread while potentially reducing phrenic nerve exposure compared with conventional interscalene block. However, direct evidence remains limited and heterogeneous, with inconsistent nomenclature, variable injectate volumes, and insufficient standardized assessment of diaphragmatic function, motor preservation, and patient-centered outcomes. Cadaveric dye studies provide anatomical plausibility but should be interpreted as indirect and hypothesis-generating evidence rather than proof of clinical efficacy or respiratory safety. Therefore, SOFPB should currently be regarded as a promising but unvalidated addition to the spectrum of diaphragm-sparing shoulder blocks rather than a replacement for established techniques. Future anatomical imaging studies, dose-finding trials, and head-to-head randomized comparisons are needed to define its optimal role in contemporary shoulder regional anesthesia.

Total-knee arthroplasty (TKA) is associated with substantial acute postoperative pain. While the adductor canal block (ACB) is widely used to provide motor-sparing anterior knee analgesia, effective management of posterior knee pain remains an important clinical challenge. The infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) block was developed to address posterior capsular pain but may be associated with technical and ergonomic limitations. More recently, the popliteal plexus block (PPB) has emerged as a novel motor-sparing alternative. This narrative review summarizes the anatomical basis, current clinical evidence, and practical considerations of combining the ACB with the PPB, with particular emphasis on its potential role as an alternative to the IPACK block within Enhanced Recovery After Surgery (ERAS) pathways. Current anatomical and early clinical evidence suggests that the PPB selectively targets the terminal articular branches around the adductor hiatus while preserving the major motor nerve trunks. Available randomized clinical trials indicate that the PPB provides analgesia comparable to IPACK while maintaining motor function, with additional practical advantages including shorter procedural time and, in individual studies, reduced postoperative opioid consumption and postoperative nausea. Overall, the combined ACB and PPB approach appears to be a promising motor-sparing strategy for perioperative analgesia after TKA. However, the current evidence is derived predominantly from cadaveric studies, early-phase randomized trials, and single-center clinical investigations. Therefore, larger multicenter studies with longer follow-ups are needed to establish its long-term efficacy, safety, and role relative to the established IPACK technique.

Low-dose naltrexone (LDN), commonly 1–6 mg/day, is increasingly used off-label for chronic pain, although evidence specific to neuropathic pain remains uncertain. We conducted a structured narrative search of PubMed/MEDLINE, CENTRAL, and ClinicalTrials.gov through 31 July 2026 and classified clinical reports by study design and reported phenotype ascertainment. No placebo-controlled randomized trial was identified in a clinically characterized neuropathic population. One randomized, double-blind, active-control crossover trial in painful diabetic neuropathy, in which both drugs were titrated by early pain response and tolerability, reported an LDN–amitriptyline difference of 1.50 mm on a 0–100 mm visual analog scale (95% confidence interval −1.11 to 4.13), with fewer short-term adverse events under LDN. Interpretation is limited by questions about the reported within-group variance and the crossover analysis, by uncertain adequacy of the treatment and washout durations, and by the absence of placebo or a prespecified equivalence margin. Placebo-controlled evidence from mixed or nociplastic populations shows no consistent clinically meaningful benefit, and its transferability to lesion-based neuropathic pain has not been demonstrated. The TLR4–microglial rationale is plausible, but measured plasma concentrations at 4.5 mg/day fall several orders of magnitude below those associated with TLR4 inhibition in vitro, whereas μ-opioid receptor occupancy is demonstrable within the LDN dose range. Current evidence supports mechanistic plausibility, not established efficacy.