Pharmacological and non-pharmacological therapies for chronic pancreatitis pain: a narrative review.

Importance: Chronic pancreatitis (CP) pain is the major driver of morbidity, reduced quality of life, healthcare use, and opioid exposure in affected patients. Pain in CP is heterogeneous and often correlates poorly with structural pancreatic abnormalities alone. It may arise from overlapping obstructive, neuropathic, nociplastic, and psychosocial mechanisms, making simple stepwise analgesic escalation insufficient for many patients. Observations: The emerging evidence supports a multidimensional strategy for treating CP pain. In some patients, pain is driven mainly by ductal obstruction, stones, strictures, inflammatory head masses, or other structural complications that may respond to endoscopic or surgical decompression. On the other hand, pain may persist because of pancreatic neuroplasticity, peripheral nerve injury, central sensitization, widespread hyperalgesia, and psychological distress. Newer tools such as the Comprehensive Pain Assessment Tool Short Form, electronic body mapping, and pancreatic quantitative sensory testing may help identify clinically relevant pain phenotypes beyond imaging alone. Although pharmacologic options remain limited, medications can provide relief in appropriately selected patients. Pregabalin has the strongest direct evidence among neuromodulators with favorable results. However, opioids remain widely prescribed even though they worsen dependency, opioid-induced hyperalgesia, and treatment resistance when used without reassessment of the dominant pain mechanism. Nonpharmacological modalities are an essential component. These include alcohol and smoking cessation, nutritional and endocrine optimization, and cognitive behavioral therapy. Endoscopic and surgical therapies are most effective when pain is anatomy-driven, while neuromodulation and other emerging interventions remain investigational but may be a promising option for nociplastic pain. Conclusions and relevance: Pain in CP should be approached as a dynamic biopsychosocial process by a multidisciplinary team. In addition to pain intensity, outcome measures should capture pain interference, function, quality of life, and opioid burden. Correctly identifying the pain phenotype and matching patients with the appropriate mechanism-based therapies and structural interventions will maximize treatment success and reduce prolonged opioid escalation and repeated low-yield interventions.