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Review
. 2025 Jul 10:16:1622845.
doi: 10.3389/fphys.2025.1622845. eCollection 2025.

Navigating chronic pancreatitis pain: a pathophysiological and therapeutic overview

Zijin Lin  1 , Stephen Pandol  2 , Minoti Apte  3 , Yi Jiang  2
Affiliations
Review

Navigating chronic pancreatitis pain: a pathophysiological and therapeutic overview

Zijin Lin et al. Front Physiol. .

Abstract

Pain management in chronic pancreatitis (CP) patients remains a major challenge, largely due to complex and refractory pain. Such pain detrimentally impacts patients by reducing quality of life, limiting daily activities, increasing psychological distress, necessitating frequent hospitalizations, and contributing to opioid dependence and socioeconomic burden. This review delineates the multifaceted nature of CP-related pain, highlighting the roles of neurogenic inflammation, maladaptive neuroplasticity, and disrupted pain modulation pathways. Current management strategies are multidisciplinary, encompassing lifestyle modification, pharmacologic therapies, endoscopic and surgical interventions, and nerve-targeted procedures (e.g., celiac plexus blocks and neurolysis). Advances in genetics, bioinformatics and biomarker research have further enhanced our understanding of CP-related pain pathogenesis, paving the way for precision medicine approaches. This review highlights current evidence and emerging innovations in the evolving landscape of CP-related pain management, emphasizing the importance of tailored and interdisciplinary care to address the intricate mechanism of CP-related pain and improve patient outcomes.

Keywords: central sensitisation; chronic pancreatitis; neurogenic inflammation; pain managemant; quality of life.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Burden of Pain from Chronic Pancreatitis. Figure created with www.biorender.com.
FIGURE 2
FIGURE 2
Innervation of the Pancreas. Parasympathetic fibers (purple) originate from the dorsal motor nucleus of the vagus in the brainstem and travel via the vagus nerve through the celiac region to reach intrapancreatic ganglia. Sympathetic fibers (blue) arise from the thoracic spinal cord, with preganglionic fibers projecting via the splanchnic nerve to synapse in the celiac ganglion; postganglionic fibers continue to the pancreas. Sensory afferents (red) from the pancreas travel back through the splanchnic nerve to the dorsal root ganglion and spinal cord, forming a bidirectional communication loop with the brain. Figure created with www.biorender.com.
FIGURE 3
FIGURE 3
Neuroimmune Interactions in Chronic Pancreatitis: Key Mediators and Pathways. PDGF-B - Platelet-derived growth factor subunit B, CXCL 12- C-X-C motif ligand 12, CNS–Central nervous system, CXCR4 – C-X-C chemokine receptor 4, IL-1β–Interleukin-1 beta, NGF–Nerve growth factor, TGF-β1 – Transforming growth factor-beta, TNF-α–Tumor necrosis factor-alpha, NGF- Nerve Growth Factor, DRG- Dorsal Root Ganglion, BDNF–Brain-Derived Neurotrophic Factor. Figure created with www.biorender.com.
FIGURE 4
FIGURE 4
Algorithm for Multimodal Pain Management in Chronic Pancreatitis. NSAIDs–Nonsteroidal anti-inflammatory drugs, ERCP–Endoscopic Retrograde Cholangiopancreatography, ESWL–Extracorporeal Shock Wave Lithotripsy, PPL–Pancreatoscopy-guided lithotripsy, DPPHR–Duodenum-preserving pancreatic head resection, CPB–Celiac plexus block, SCS–Spinal cord stimulation, TMS–Transcranial magnetic stimulation. Figure created with www.biorender.com.
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