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.