Abstract:Objective To investigate the efficacy of perioperative oral gabapentin in multimodal analgesia following free anterolateral thigh flap repair surgery, and its impact on pain, anxiety, depression, and fatigue in patients. Methods A total of 104 patients who underwent free anterolateral thigh flap repair surgery in the Department of Hand Surgery, Wuxi Ninth People’s Hospital from January to June 2024 were selected and randomly divided into a control group (n=52) and a study group (n=52). Both groups received patient-controlled intravenous analgesia (PCIA) postoperatively with sufentanil 2 μg/kg combined with tropisetron 6 mg. The study group received oral gabapentin 0.6 g one hour before surgery and 0.9 g daily for four consecutive days postoperatively. while the control group took inactive capsules with the same appearance in exactly the same way as the research group. Resting Visual Analog Scale (VAS) scores, Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), and Christensen Fatigue Score were recorded preoperatively and at 24, 48, and 72 hours postoperatively. Adverse reactions (dizziness, nausea and vomiting, vascular crisis) within 72 hours postoperatively, as well as serum levels of inflammatory factors [interleukin (IL) -6, tumor necrosis factor (TNF) -α]and nerve growth factor (NGF), were monitored. Results Compared to the control group, the study group showed significantly lower resting VAS score at 24, 48, and 72 hours postoperatively (P<0.01). The PSQI and Christensen Fatigue Score at 48 and 72 hours postoperatively, and the HADS score at 72 hours postoperatively, were significantly lower in the study group than in the control group (P<0.05). Postoperative levels of IL-6 and TNF-α were significantly lower in the study group (P<0.05), while NGF levels were significantly higher. at 24, 48 and 74 hours postoperatively (P<0.05) Compared with the control group, the study group had a lower rate of rescue analgesia use [5.77% (3/52) vs 34.62% (18/52), χ²=13.425, P=0.002], fewer daily rescue analgesia administrations [ (0.6±0.3) times vs (1.8±0.7) times, t=11.362, P<0.01], lower total sufentanil consumption [ (12.5±2.1) μg/kg vs (18.3±3.4) μg/kg, t= 10.466, P<0.01], and fewer postoperative PCIA attempts [ (8.2±1.5) times vs (14.7±2.8) times, t=14.756, P<0.01]. There was no statistically significant difference between the two groups in the incidence of adverse reactions such as dizziness, nausea and vomiting, and vascular crisis (P>0.05). Conclusion Gabapentin combined with multimodal analgesia can effectively relieve pain, anxiety, and fatigue, improve sleep quality, modulate inflammatory responses, and promote nerve regeneration after free anterolateral thigh flap repair surgery, demonstrating good safety.