Pathophysiology, assessment, and treatment of pain in patients with pancreatic ductal adenocarcinoma

Pain is one of the most frequent and debilitating symptoms associated with pancreatic ductal adenocarcinoma (PDAC). More than 60% of patients suffer from significant pain at diagnosis. The prevalence increases during the progression of the disease and is associated with anorexia, weight loss, and impaired social interactions. The pathophysiology of pain includes the combined effects of tumor growth and spread, perineural invasion, neuroimmune interactions, peripheral nerve remodeling, and central nervous system sensitization. Pain is additionally modulated by comorbid conditions, such as anxiety or depression, as well as treatment-related toxicity. Previous reports have used simple unidimensional scales to assess pain intensity, but as pain in PDAC is multidimensional, there is a need to develop new and robust instruments to assess pain. The treatment follows the World Health Organization three-step analgesic ladder. Non-opioid analgesics can be used to improve pain, but strong opioids are often used to relieve pain and suffering. When opioids are used, there should be a focus on the management of the side effects. Patients with anxiety and depression may benefit from treatment with selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, and tricyclic antidepressants that also have effects on pain. In some cases, more experimental drugs such as ketamine may be used. Celiac plexus neurolysis and local irradiation therapies are supplementary methods used to treat PDAC pain, but the response is unpredictable, and the durability is relatively short. The reduced survival associated with celiac ganglia injection, especially in patients with advanced disease, has also tempered enthusiasm.