Acute pancreatitis results in referred mechanical hypersensitivity and
neuropeptide up-regulation that can be suppressed by the protein kinase
inhibitor k252a.
Winston JH, Toma H, Shenoy M, He ZJ, Zou L, Xiao SY, Micci MA, Pasricha PJ.
Enteric Neuromuscular Disorders and Pain Group, Division of Gastroenterology and
Hepatology, Department of Internal Medicine, University of Texas Medical Branch,
Galveston, Texas 77555, USA.
Although pain is a cardinal feature of pancreatitis, its pathogenesis is poorly
understood and treatment remains difficult. Nociceptive sensitization in several
somatic pain models has been associated with activation of protein kinases
including trkA, protein kinase C, and protein kinase A. We therefore tested the
hypothesis that systemic treatment with a kinase inhibitor, k252a, known to
inhibit all of these kinases would alleviate pain in an animal model of
pancreatitis. Von Frey filament testing of somatic referral regions was
evaluated as a method to measure referred pain in a rat model of acute
necrotizing pancreatitis induced by L-arginine. Rats with pancreatitis showed
increased sensitivity to abdominal stimulation with Von Frey filament. This
referred mechanical sensitivity was associated with an 8-fold increase in levels
of phosphorylated trkA in the pancreas and with significant up-regulation of
both calcitonin gene-related peptide and preprotachykinin mRNA expression in
thoracic dorsal root ganglia and with increased calcitonin gene-related peptide
and substance P immunoreactivity in spinal cord segment T10. Treatment with the
kinase inhibitor k252a suppressed the phosphorylation of trkA in the pancreas as
well as reversed both the behavioral changes and the increase in neuropeptide
expression associated with pancreatitis.
Publication Types:
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