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Winston JH, Toma H, Shenoy M, He ZJ, Zou L, Xiao SY, Micci MA, Pasricha PJ.
Acute pancreatitis results in referred mechanical hypersensitivity and
neuropeptide up-regulation that can be suppressed by the protein kinase
inhibitor k252a.
J Pain. 2003 Aug;4(6):329-37.
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.
PMID: 14622690 |
