Severe Pain in Chronic Pancreatitis Patients: Considering Mental Health and Associated Genetic Factors

Abstract

Pain is the most distressing and disruptive feature of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) resulting in low quality of life (QOL) and disabilities. There is no single, characteristic pain pattern in patients with RAP and CP. Abdominal imaging features of CP accurately reflect morphologic features but they do not correlate with pain. Pain is the major driver of poor quality of life (QOL) and it is the constant pain, rather than intermittent pain that drives poor QOL. Furthermore, the most severe constant pain experience in CP is also a complex condition. The ability to target the etiopathogenesis of severe pain requires new methods to detect the exact pain mechanisms in an individual at cellular, tissue, system and psychiatric levels. In patients with complex and severe disease, it is likely that multiple overlapping mechanisms are simultaneously driving pain, anxiety and depression. Quantitative sensory testing (QST) shows promise in detecting alterations in central processing of pain signals and to classify patients for mechanistic and therapeutic studies. New genetic research suggests that genetic loci for severe pain in CP overlap with genetic loci for depression and other psychiatric disorders, providing additional insights and therapeutic targets for individual patients with severe CP pain. Well-designed clinical trials that integrate clinical features, QST, genetics and psychological assessments with targeted treatment and assessment of responses are required for a quantum leap forward. A better understanding of the context and mechanisms contributing to severe pain experiences in individual patients is predicted to lead to better therapies and quality of life.

Pain Experience in Pancreatitis: Strong Association of Genetic Risk Loci for Anxiety and PTSD in Patients With Severe, Constant, and Constant-Severe Pain

“…The poor QOL experienced by many patients with pancreatitis is linked to the pain experience, which is affected by pain signaling, central processing, and the emotional response to those signals (1,(15)(16)(17)41). We previously noted that symptoms of depression in RAP and CP are associated with constant-severe pain and genetic loci containing depression risk genes (24).…”

Characterizing mechanism-based pain phenotypes in patients with chronic pancreatitis: a cross-sectional analysis of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies

“…Furthermore, anxiety and depression exacerbate the pain experience. 9 Given that the Both and Neuropathic-like only pain groups had worse anxiety and depression, we expected that these groups would have higher neuromodulator use. However, there was no significant difference in the prevalence of neuromodulator (eg, gabapentin or antidepressant) use between pain groups.…”

Chemical pancreatectomy in non-human primates ablates the acini and ducts and enhances beta-cell function

“…These longterm sequelae of chronic pancreatitis are challenging to treat and expensive to manage over a patient's disease progression. Chronic pain often requires treatment with opioids, frequently leading to dependence and addiction 5,6 . In addition, patients often have exocrine pancreatic insu ciency necessitating lifelong pancreatic enzyme supplementation.…”