Severe chronic pain syndrome with high requirement for opioids is frequently complicated by opioid tolerance, hyperalgesia, and other side effects. Special complications occur during anesthesia for high-injury surgical interventions and in the postoperative period. Perioperative pain management in these patients requires planning, multimodal approach, combination methods, and prevention of complications including specific complications. This article describes a case of successful surgical treatment of pancreatic cancer in a patient with severe chronic pain syndrome, opioid tolerance, and hyperalgesia. Perioperative period was complicated by high requirement for epidural pain management and use of adjuvants, acute strangulating intestinal obstruction on day 6 of the postoperative period. The authors had to differentiate between pain syndrome and abstinence multiple times and encountered the problem of tachyphylaxis to local anesthetics. Due to thought-out and flexible system of combination multimodal pain management, pain syndrome was relieved, and the patient was discharged in satisfactory condition without the need for opioids.