Abstract
We examined if TRPA1, like TRPV1, contributes to pancreatic nociceptor excitation following proteinase-activated receptor-2 (PAR2) stimulation and to pancreatitis-related pain in mice. A PAR2-activating peptide, infused into the pancreatic duct, caused spinal Fos expression, which was prevented by AP18, a TRPA1 inhibitor. Repeated administration of cerulein caused referred hyperalgesia accompanying pancreatitis, which was reversed by SB366791, a TRPV1 inhibitor, but not AP18. AP18, administered in combination with a subeffective dose of SB366791, significantly suppressed the referred hyperalgesia. Our findings suggest that TRPA1, like TRPV1, mediates PAR2-triggered pancreatic nociception and that TRPA1 in collaboration with TRPV1 latently contributes to pancreatitis-related pain.
MeSH terms
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Anilides / administration & dosage
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Anilides / pharmacology
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Animals
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Cinnamates / administration & dosage
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Cinnamates / pharmacology
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Hyperalgesia / drug therapy
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Hyperalgesia / etiology
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Hyperalgesia / genetics*
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Hyperalgesia / physiopathology
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Male
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Mice
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Mice, Inbred Strains
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Nociception / physiology
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Pancreatitis / complications*
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Receptor, PAR-2 / physiology*
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Signal Transduction / genetics*
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Signal Transduction / physiology*
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TRPA1 Cation Channel
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TRPV Cation Channels / physiology*
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Transient Receptor Potential Channels / antagonists & inhibitors
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Transient Receptor Potential Channels / physiology*
Substances
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Anilides
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Cinnamates
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N-(3-methoxyphenyl)-4-chlorocinnamanilide
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Receptor, PAR-2
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TRPA1 Cation Channel
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TRPV Cation Channels
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TRPV1 protein, mouse
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Transient Receptor Potential Channels
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Trpa1 protein, mouse