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Beyond Unconsciousness: Optimizing Antinociception during General Anesthesia. Perioperative analgesia is an essential component of anesthesia, yet the intraoperative management of surgical nociception remains underdiscussed. This gap largely reflects our incomplete understanding of how the central nervous system is activated by noxious surgical stimulation (nociception) during general anesthesia, and what neurophysiologic "targets" intraoperative antinociception should aim for. Although it is widely accepted that general anesthesia renders patients unconscious and eliminates the experience of pain, modern neurophysiologic techniques show that the central nervous system's processing of nociceptive input is only partially suppressed, even during deep anesthesia. There are potential benefits and risks in more intense mitigation of these responses. Clinicians often rely on bedside judgment and physiologic signs to treat intraoperative nociception. Such heuristic practice makes it unlikely that antinociceptive regimens are individualized or optimized for each patient. This review examines the evolving concept of intraoperative nociception, its underlying physiologic and neurobiological mechanisms, and consequences, as well as the clinical strategies employed to assess and optimize antinociception regimens.