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Surgery-associated tissue injury leads to nociception and inflammatory reaction, accompanied by increased production of proinflammatory cytokines. These cytokines can induce peripheral and central sensitization, leading to pain augmentation. Recently, a frequently used local anesthetic, lidocaine, was introduced as a part of a perioperative pain management technique. In addition to its analgesic effects, lidocaine has an antiinflammatory property, decreasing the upregulation of proinflammatory cytokines. We focused on the effects of preincisional and intraoperative IV lidocaine on pain intensity and immune reactivity in the postoperative period.Sixty-five female patients (ASA physical status I–II) scheduled for transabdominal hysterectomy were recruited to this randomized, placebo-controlled study. Thirty-two patients in the treatment group received IV lidocaine starting 20 min before surgery, whereas the control group (33 patients) received a matched saline infusion. Both groups received patient-controlled epidural analgesia during the postoperative period. Blood samples were collected before, 24, 48, and 72 h after surgery to measure ex vivo cytokine production of interleukin (IL)-1 receptor antagonist (IL-1ra) and IL-6, as well lymphocyte mitogenic response to phytohemagglutinin-M. A 10-cm visual analog scale was used to assess pain intensity at rest and after coughing.Patients in the lidocaine + patient-controlled epidural analgesia group experienced less severe postoperative pain in the first 4 and 8 h after surgery (visual analog scale 4/3.7 at rest and 5.3/5 during coughing versus 4.5/4.2 and 6.1/5.3, respectively, in the placebo group). There was significantly less ex vivo production of IL-1ra and IL-6, whereas the lymphocyte proliferation response to phytohemagglutinin-M was better maintained than in the control group.The present findings indicate that preoperative and intraoperative IV lidocaine improves immediate postoperative pain management and reduces surgery-induced immune alterations.