Types

1
Choudhuri Mechanisms of pain in chronic
pancreatitis
Characteristics of pain

• Types
• Type A
• Type B
• Intensity
• Duration
• Radiation
• Other factors drug dependence, QOL

Rudolf W et al. Gastroenterology 1999
2
Choudhuri Mechanisms of pain in chronic
pancreatitis
Pathophysiology of CP

• Pancreatic causes
• Increased pressure in ducts and tissue
• Acute inflammation of the pancreas
• Pancreatic ischemia
• Pancreatic fibrosis
• Pancreatic pseudocysts
• Alteration of pancreatic nerves
• Neuro-immune interaction
• Extra-pancreatic causes
• Duodenal stenosis
• CBD stenosis
• Maldigestion

3
Choudhuri Mechanisms of pain in chronic
pancreatitis
Increased ductal pressure and acute inflammation

• Increased ductal pressure
• Obstruction due to strictures or stones
• Dilated MPD
• Related to secretion ? pain with octreotide
• Cholecystokinin mediated
• Relief with pancreatic enzymes
• Decompression relieves pain
• Pancreatic exocrine insufficiency ? ? pain
• Acute inflammation of the pancreas
• Inflammation ? activation of enzymes injurious
  substances ? pain
• ? expression of neurotrophin (nerve growth factor
  NGF) during AP in rats
• NGF gene expression ? pain intensity in humans

4
Choudhuri Mechanisms of pain in chronic
pancreatitis
Pancreatic ischemia, fibrosis, and pseudocysts

• Pancreatic ischemia
• ? Interstitial pressure ? ? blood flow
• Compartment syndrome
• Reversed by surgical incision of gland and PD
  drainage
• Less affected by stenting
• Pancreatic fibrosis
• Cause strictures ? ? ductal pressure
• No direct correlation
• Pancreatic pseudocysts
• Commonly associated with pain
• Communicating
• ? size ? ? pain
• Octreotide pain relief in 60 by reducing size?
  pressure?

5
Choudhuri Mechanisms of pain in chronic
pancreatitis
Alteration in pancreatic nerves, and neuro-immune
interactions

• Alteration in pancreatic nerves
• Pain ? perineural eosinophils Keith, 1985
• Enlarged nerves, damaged perineurium Backman,
  1988
• ? neuropeptide expression Buchler, 1992
• Growth assoc protein (GAP-43) expression Fink,
  1994
• Nerve growth factor (NGF) TrKA receptor Freiss,
  1999
• ? Interleukin 8 gene expression Sebastiano,
  2003
• Neuropeptides and cytokines in brain
  Shrikande, 2000
• Neuro-immune interactions
• Direct relationship between degree of
  peri-neuritis and pain
• Suggests important role in pain generation
• NGF/TrkA pathway?activated in CP, may influence
  pain
• Neuro-immune cross talk exact mechanism is not
  clear

6
Choudhuri Mechanisms of pain in chronic
pancreatitis
Natural history of pain

• Initially Type A pain
• associated with acute attacks of inflammation
• Pain of CP Type B
• Obstructive
• Burn-out theory
• Spontaneous relief in some after 4.5 y
• Associated with exocrine failure calcification
• Late pain
• Recurrence after surgery in 30
• Peri-pancreatic fibrosis
• Perineural involvement
• Mechanisms of pain are possibly multiple, and
  depend on the stage of the disease.