Background: Perioperative multimodal analgesia can prevent chronic pain after breast cancer surgery. This study aimed to investigate the efficacy of combined perioperative oral pregabalin and postoperative esketamine in preventing chronic pain after breast cancer surgery.Methods: Ninety patients undergoing elective breast cancer surgery were randomized into the combined pregabalin and esketamine group (EP group) and the general anesthesia alone group (Control group). The EP group received 150 mg of oral pregabalin 1 h before surgery and twice daily for seven days postoperatively, and a patient-controlled analgesia pump after surgery that delivered 100 mu g sufentanil + 1.25 mg/kg esketamine + 4 mg tropisetron in 100 mL saline solution intravenously. The Control group received placebo capsules before and after the surgery and routine postoperative analgesia (100 mu g sufentanil + 4 mg tropisetron in 100 mL saline solution). The primary outcome was the incidence of chronic pain three and six months after surgery. Secondary outcomes included acute postoperative pain, postoperative opioid consumption, and incidence of adverse events.Results: The incidence of chronic pain in the EP group was significantly lower than in the Control group three (14.3% vs 46.3%, P = 0.005) and six (7.1% vs 31.7%, P = 0.009) months postoperatively. The rest numerical rating scale (NRS) pain scores 1-3 days postoperatively and coughing NRS pain scores 1-7 days postoperatively in the EP group were significantly lower than in the Control group (all P < 0.05). The cumulative sufentanil consumption in the EP group during postoperative 0-12, 12-24, and 24-48, 0-24, and 0-48 hours were significantly lower than in the Control group (all P < 0.05).Conclusion: Combined perioperative oral pregabalin and postoperative esketamine effectively prevented chronic pain after breast cancer surgery, improved acute postoperative pain, and reduced postoperative opioid consumption.

Objective To investigate the effect of esketamine combined with ketorolac tromethamine in preventing remifentanil-induced hyperalgesia.Methods Sixty patients undergoing elective laparoscopic total hysterectomy under general anesthesia were randomly assigned into two groups with 30 cases each. The patients of group EK received intravenous ketorolac tromethamine 15 mg on 20 minutes before induction of anesthesia and esketamine 0.125 mg/kg on 10 minutes before skin incision. The patients of group C were intravenously injected with the same volume of normal saline at the time points. The mechanical pain thresholds around the incision and medial dominant arm were measured before operation and at 12,24 and 48 hours after operation. The resting and cough pain numerical rating scale（NRS） scores at 3,6,12,24 and 48 hours after operation were recorded. The sufentanil consumption during 0-6,7-12,13-18,19-24 and 0-24 hours after operation and the first time of analgesic use were recorded. The adverse reactions within 48 hours after operation were observed.Results The mechanical pain thresholds around the incision and medial dominant arm were lower in group C at 12, 24 and 48 hours after operation, and those were lower in group EK at 48 hours after operation than those before operation（P＜0.05）. Compared with group C, the mechanical pain thresholds around the incision and medial dominant arm were increased at 12 and 24 hours after operation, resting NRS scores were decreased at 3, 6 and 12 hours after operation, cough NRS scores were decreased at 3, 6, 12 and 24 hours after operation, sufentanil consumptions were decreased during 0-6,7-12,13-18,19-24 and 0-24 hours after operation, and the first time of analgesic use was prolonged in group EK（P＜0.05）. The incidence of adverse reactions after surgery was not significantly different between the two groups（P＞0.05）.Conclusion Esketamine combined with ketorolac tromethamine can effectively prevent remifentanil-induced hyperalgesia after laparoscopic total hysterectomy without increasing adverse reactions.