Visceral pain shares several mechanisms across organs, including nociceptor activation, peripheral sensitization, neuroimmune signaling, and central sensitization. Pancreatic pain, however, can be severe, difficult to treat, and particularly complex because these shared pathways coexist with distinct forms of local tissue and neural injury. Toxic, metabolic, inflammatory, mechanical, and malignant processes may overlap within the pancreas. Their effects are shaped by neural, immune, and stromal signaling, while possible neuroendocrine contributions remain an important area for investigation.

Pancreatic injury does more than damage tissue. It can sensitize nociceptors and alter the structure and function of pancreatic nerves, leading to peripheral sensitization, perineural inflammation, nerve hypertrophy, and broader neural remodeling. In pancreatic cancer, tumor cells can infiltrate perineural spaces and spread along nerves, a process known as perineural invasion. This can cause neural injury and contribute to pain, while bidirectional signaling between tumor cells and nerves may also promote disease progression. Clinically, pancreatic pain is often diffuse, difficult to localize, and referred to the back. In chronic pancreatitis, its severity may correlate poorly with the extent of inflammation, fibrosis, or structural change. Pain may persist after the initial injury has subsided or an obstruction has been treated, while some patients with substantial pancreatic disease report little or no pain.
This mismatch suggests that pain does not simply reflect the extent of tissue damage. Its pattern, persistence, and response to treatment may help distinguish pain driven mainly by active pancreatic pathology from pain sustained by peripheral sensitization, neural injury, or altered spinal and brain processing. At the heart of this Research Topic is a clear question: What can pain tell us about the nature of pancreatic injury, and how can that knowledge guide treatment? The collection will trace pancreatic pain from tissue injury and nociceptor activation to neural remodeling, central sensitization, and treatment response.

Themes central to the collection:

1. Organ-Specific Injury and Pain Initiation
Alcohol-related, drug-induced, toxic, and metabolic pancreatic injury
Acinar and ductal cell injury, oxidative stress, ischemia, and inflammation
Fibrosis, ductal obstruction, pressure, and other mechanical drivers
Pancreatic nociceptors, ion channels, and sensory receptors
Neural, immune, stromal, and potential neuroendocrine contributions to pain
Comparative mechanisms of nociception across visceral organs

2. Peripheral Sensitization and Neural Remodeling
Peripheral nociceptor sensitization and neurogenic inflammation
Pancreatic neuritis, nerve hypertrophy, altered nerve density, and neuropathic remodeling
Axonal injury and regeneration
Interactions among Schwann cells, immune cells, stromal cells, and neurons
Perineural inflammation and fibrosis
Tumor cell invasion of perineural spaces and bidirectional tumor-nerve signaling
Organ-specific patterns of visceral neural plasticity

3. From Pancreatic Signals to Central Pain Processing
Neuroimmune signaling and glial activation
Spinal cord sensitization and descending pain modulation
Brain network changes associated with pancreatic pain
Referred abdominal and back pain
Viscero-visceral convergence and cross-organ sensitization
Progression from episodic to persistent pain
Neuropathic and nociplastic features of pancreatic pain
Shared and distinct central pathways across visceral pain conditions

4. Mechanism-Based Phenotyping and Treatment
Nociceptive, neuropathic, and nociplastic pain features
Quantitative sensory testing, neurophysiology, and patient-reported outcomes
Structural, functional, and molecular imaging
Biomarkers of pain persistence and treatment response
Nonopioid pharmacologic targets
Neuromodulation and nerve-directed interventions
Mechanistic evaluation of endoscopic and surgical treatments
Opioid-induced hyperalgesia and opioid-sparing strategies
Transferable therapeutic targets across visceral organs
Precision analgesia based on dominant pain mechanisms

Scope note
The primary focus is pain associated with acute, recurrent acute, and chronic pancreatitis; pancreatic cancer; and pancreatic procedures or interventions. Comparative studies involving the stomach, intestine, liver, biliary system, or other visceral organs may be included when they clarify a pancreatic mechanism, identify a shared pathway, or provide a meaningful comparison.
This scope keeps the pancreas at the center while opening the collection to pain neuroscientists and researchers working across visceral systems. It will help distinguish the mechanisms shared across visceral pain conditions from those shaped by the distinctive biology and innervation of the pancreas.

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Pancreatic Pain Across the Neural Axis: Organ-Specific Drivers and Shared Mechanisms of Visceral Pain