Maxillofacial trauma is the tenth leading cause of morbidity and mortality, according to the World Health Organization (Lee, 2012). Road traffic accidents, assaults, and workplace and sports injuries are the most common causes (Rowe and Williams, 1994). Zygomatic fracture (43.9%) is the most common facial fracture, followed by mandibular (33%) and nasal bone fractures (24.5%), because of their prominent facial positions (Yamsani et al., 2016).

Fracture lines of the zygomaticomaxillary complex (ZMC) often involve the infraorbital foramen, canal, or fissure (Sakavicius et al., 2008). Consequently, sensory neuropathy in the area innervated by the infraorbital nerve (IO) can be both a presenting symptom and a postoperative complication (Kumar et al., 2012; Noor et al., 2017). This sensory deficit ranges from 58% to 94% (Vriens et al., 1998).

Injury to the IO nerve is caused mainly by direct trauma or by secondary mechanisms, such as a blunt, crush injury, or bony compression of the nerve at the fracture site (Taicher et al., 1993). The regenerative capacity of such wounds is a controversial topic in the literature. The speed of sensory recovery depends on several factors, including the nature and extent of the nerve injury, the time between the injury and surgical intervention, and the method of treatment (Kumar et al., 2012). Although many medical management strategies, such as multivitamin supplements and steroids, have been tested to accelerate recovery, there are no widely accepted and effective treatments reported in the literature.

Melatonin (N-acetyl-5-methoxytryptamine), which is often associated with the management of anxiety and sleep disorders, has an almost universal physiological effect because almost all cells in the body have melatonin receptors (Liu et al., 2016; Emet et al., 2016). Its analgesic action is dose-dependently mediated through centrally located pain receptors (Yu et al., 2000; Yousaf et al., 2010). It is also a strong antioxidant due to its ability to activate enzymes responsible for maintaining the intracellular and intramitochondrial balance of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) produced from normal metabolism (Mehrzadi et al., 2017). These antioxidant enzymes include catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), which can catalyze the breakdown of ROS into water, thereby neutralizing their harmful effects (Birben et al., 2012). Both ROS and H2O2 are involved in pain and abnormal nerve function. Melatonin promotes healing by providing ischemic protection, inhibiting mitochondrial death, and stimulating neurogenesis through its ability to induce antioxidant enzymes (Lee et al., 2017; Areti et al., 2017; Lee and Curtin, 2020; Daglioglu et al., 2009; Zhu et al., 2017).

Human research has primarily focused on the analgesic effects of melatonin in trauma patients. However, melatonin has also significantly increased axonal regeneration in animals after injury (Kaya et al., 2015; Fujimoto et al., 2000). Adverse effects of exogenous melatonin administration are rare, even with high-dose intravenous administration (Andersen et al., 2016). Therefore, our study hypothesized that perioperative melatonin can alleviate postoperative pain and increase the speed of sensory recovery following zygomaticomaxillary fractures, through its antioxidant effects.