Prophylactic Management of Radiotherapy-Induced Neuropathic Pain in Head and Neck Cancer: A Randomized Controlled Trial

Introduction: Radiotherapy for head and neck cancer frequently causes debilitating neuropathic pain. Conventional analgesics are often inadequate, highlighting a critical need for effective preventive measures. Therefore, this randomized controlled trial was designed to evaluate the efficacy of prophylactic pregabalin in managing radiotherapy-induced neuropathic pain in head and neck cancer patients. Material and methods: This double-blind randomized clinical trial evaluated 60 head and neck cancer patients (30 per group) at Shahid Madani Hospital to investigate the preventive efficacy of prophylactic pregabalin on radiotherapy-induced neuropathic pain. Serial pain scores, analgesic requirements, adverse events, and treatment tolerance were prospectively tracked throughout the radiotherapy course. Results: Prophylactic pregabalin significantly attenuated radiation-induced neuropathic pain compared to control (peak mean 2.30±0.60 vs 7.20±1.00; p<0.05), reduced cumulative opioid consumption (42.0±12.8 mg vs 145.5±22.4 mg; p<0.05), decreased rescue medication reliance (23.3% vs 76.7%), and lowered breakthrough pain frequency (1.2±0.4 vs 4.8±1.1; p<0.05), while maintaining an acceptable and manageable safety profile without severe adverse events. Conclusion: Preemptive administration of pregabalin offers an effective, opioid-sparing therapeutic strategy for managing radiotherapy-induced neuropathic pain in head and neck cancer patients. Despite mild, self-limiting central nervous system side effects such as dizziness and somnolence, the favorable efficacy and tolerability profile support its routine clinical implementation to enhance patient comfort and quality of life during oncological radiation therapy.