Perioperative pain remains a major clinical challenge, with many surgical patients experiencing inadequate analgesia and progression to chronic postsurgical pain. Conventional opioid-centered strategies are limited by narrow therapeutic windows, systemic toxicity, tolerance, opioid-induced hyperalgesia, and poor efficacy in neuroimmune-driven pain states. Advances in molecular neuroscience and biomedical engineering have catalyzed the development of nonpharmacologic analgesic technologies that modulate pain pathways through biophysical rather than receptor–ligand mechanisms. This narrative review synthesizes emerging nonpharmacologic analgesic platforms relevant to anesthesiology, integrating molecular, cellular, and systems-level mechanisms with clinical evidence. It examines how peripheral sensitization, spinal dorsal horn plasticity, glial and neuroimmune activation, and supraspinal network dysfunction create ideal targets for device-based interventions. Electrical neuromodulation strategies, including peripheral and central techniques, are discussed alongside temperature-based, photonic, and focused-energy modalities. These include cryoneurolysis, radiofrequency techniques, photobiomodulation, and low-intensity focused ultrasound. Clinical integration within enhanced recovery pathways, patient selection, workflow considerations, and limitations of the current human evidence base are reviewed. While many of these technologies are established in chronic pain management, this review emphasizes available human perioperative data and discusses how chronic pain evidence informs perioperative translation within opioid-sparing multimodal anesthesia care. Collectively, these technologies support a mechanism-based, systems-level approach to pain modulation, with perioperative relevance varying by modality and strength of available human evidence.
McKenzie et al. (Tue,) studied this question.