Pain management in chronic pancreatitis: beyond opioids.

Chronic pancreatitis is characterised by complex, multifactorial pain affecting 80-90% of patients. Pain arises from overlapping nociceptive and neuropathic mechanisms, often accompanied by CNS sensitisation and reorganisation that amplify symptoms (nociplastic pain). Opioid use is highly prevalent in chronic pancreatitis despite its many side-effects and addictive potential, and there is a need for alternative treatment strategies. Non-opioid pharmacological treatments, including neuromodulators, target specific pain mechanisms, with gabapentinoids showing the strongest evidence. Other interventions, such as cognitive behavioural therapy, antioxidants, dietary strategies, and lifestyle modification, might provide additional benefit, but high-quality evidence remains scarce. Endoscopic and surgical interventions relieve obstructive disease; however, the evidence base has a shortage of sham-controlled trials, complicating the interpretation of treatment effect. Emerging approaches, including novel neuromodulatory and anti-inflammatory therapies and integration of pharmacological and non-pharmacological treatments, hold promise for improving pain control. Multidimensional assessment, combining patient-reported outcomes, quantitative sensory testing, imaging, and emerging biomarkers, enables pain phenotyping and could support more individualised and more effective management, guiding multimodal strategies. Future research should prioritise mechanism-based trials, refined patient phenotyping, and predictive biomarkers to guide personalised therapies.