Introduction Migraine is a highly prevalent neurological disorder that affects about 15% of the world's population. Involved in migraine pain, the cranial dura mater is a richly vascularized and innervated membrane, where we also find mast cells, and immune cells that help in the formation of the inflammatory process. As one of the treatments for migraine, we have melatonin, a hormone produced in the pineal gland and with properties such as circadian cycle control and antioxidant action. Capsaicin, a bioactive compound found in peppers and with a pungent and burning effect, also has an action in the painful process and serves as a tool in the study of physiopathogenic processes. Objectives To evaluate the degranulation of dura mater mast cells from Wistar rats stimulated in situ with capsaicin and synthetic interstitial fluid (SIF) and previously treated with melatonin. Methods Twenty-five male Wistar rats were used, obtained from the Department of Antibiotics - Danti of the Federal University of Pernambuco - UFPE and with use authorized by the Ethics Committee in the Use of Animals - CEUA of UFPE, according to protocol nº 0084/2019. During the adaptation period, the animals were acclimatized under standard laboratory conditions, with water and food ad libitum. After this period, they were separated into two groups: a control group (CG) (n = 12) and a melatonin group (GM) (n = 13), and underwent a daily treatment for 10 days with the intraperitoneal application. The GM received a dosage of 10 mg/kg of the animal weight of melatonin diluted in a saline solution at 0.9% and the GC was treated only with the vehicle. After the treatment, the animals were anesthetized and submitted to an experimental surgery... (To see the complet abstract, please, check out the PDF.)