The proteinase/proteinase-activated receptor-2/transient receptor potential vanilloid-1 cascade impacts pancreatic pain in mice

Nishimura, Sachiyo; Ishikura, Hiroyasu; Matsunami, Masatoshi; Shinozaki, Yui; Sekiguchi, Fumiko; Naruse, Mitsuhide; Kitamura, Taisuke; Akashi, Ryukichi; Matsumura, Kenji; Kawabata, Atsufumi

doi:10.1016/j.lfs.2010.09.030

Cited by 19 publications

(20 citation statements)

References 39 publications

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“…1A), and significant increase in the number of Fos-positive cells, most clearly in laminae I-II of T8 -T10 spinal segments (Fig. 1B), in agreement with the previous report (4). AP18, the TRPA1 inhibitor, preadministered i.p.…”

Section: Short Communicationsupporting

confidence: 93%

“…† † P < 0.01, † † † P < 0.001 vs. cerulein + vehicle. expression suggest the pro-nociceptive role of TRPA1, in addition to TRPV1 (3,4), as downstream signals of PAR2 activation in the pancreas. This is consistent with evidence for trans-activation of TRPA1 as well as TRPV1 following PAR2 stimulation (6 -9).…”

Section: Short Communicationmentioning

confidence: 96%

“…PAR2 also mediates pancreatic pain signaling (1, 3 -5). The trans-activation of transient receptor potential vanilloid-1 (TRPV1) by PAR2 activation is involved in the development of somatic pain (6 -8) and also pancreatitis-related pain (3,4). On the other hand, trans-activation of transient receptor potential ankyrin-1 (TRPA1) by PAR2 activation contributes to inflammatory pain (9).…”

Section: Short Communicationmentioning

confidence: 99%

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Contribution of TRPA1 as a Downstream Signal of Proteinase-Activated Receptor-2 to Pancreatic Pain

et al. 2013

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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.

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Section: Short Communicationsupporting

confidence: 93%

Section: Short Communicationmentioning

confidence: 96%

Section: Short Communicationmentioning

confidence: 99%

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Contribution of TRPA1 as a Downstream Signal of Proteinase-Activated Receptor-2 to Pancreatic Pain

et al. 2013

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“…Among various “pronociceptive” ion channels expressed in nociceptors, transient receptor potential vanilloid-1 (TRPV1) channels and Ca v 3.2 T-type Ca 2+ channels play critical roles in the development of pancreatitis-related pain [1,2,3,4]. TRPV1 is directly phosphorylated and sensitized by protein kinase C (PKC), particularly following the activation of proteinase-activated receptor-2 (PAR2), a Gq protein-coupled receptor, known to be expressed in nociceptors [5].…”

Section: Introductionmentioning

confidence: 99%

“…TRPV1 is directly phosphorylated and sensitized by protein kinase C (PKC), particularly following the activation of proteinase-activated receptor-2 (PAR2), a Gq protein-coupled receptor, known to be expressed in nociceptors [5]. During acute pancreatitis, pancreatic trypsin activates PAR2 by unmasking the N-terminal receptor-activating sequence, leading to TRPV1-dependent pancreatic pain [1,3]. The activity of Ca v 3.2 T-type Ca 2+ channels is enhanced by endogenous hydrogen sulfide during pancreatitis, contributing to pancreatic pain [2].…”

Section: Introductionmentioning

confidence: 99%

Tacrolimus Triggers Transient Receptor Potential Vanilloid-1-Dependent Relapse of Pancreatitis-Related Pain in Mice

et al. 2017

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Transient receptor potential vanilloid-1 (TRPV1) expressed in nociceptors is directly phosphorylated and activated by protein kinase C, and involved in the signaling of pancreatic pain. On the other hand, Ca_v3.2 T-type Ca²⁺ channels expressed in nociceptors are functionally upregulated by phosphorylation with protein kinase A and also play a role in pancreatitis-related pain. Calcineurin, a phosphatase, negatively regulates various channel functions including TRPV1, and calcineurin inhibitor-induced pain syndrome by tacrolimus, a calcineurin inhibitor, used as an immunosuppressant, has been a clinical problem. We thus examined the effect of tacrolimus on pancreatitis-related pain in mice. Repeated treatment with cerulein caused referred hyperalgesia accompanying acute pancreatitis, which was unaffected by tacrolimus. Pancreatitis-related symptoms disappeared in 24 h, whereas the referred hyperalgesia recurred following the administration of tacrolimus, which was abolished by the blockers of TRPV1 but not T-type Ca²⁺ channels. Thus, tacrolimus appears to cause the TRPV1-dependent relapse of pancreatitis-related pain, suggesting the involvement of calcineurin in the termination of pancreatic pain.

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Protease‐activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain

Liu

Yue

et al. 2013

European Journal of Pain

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The proteinase/proteinase-activated receptor-2/transient receptor potential vanilloid-1 cascade impacts pancreatic pain in mice

Cited by 19 publications

References 39 publications

Contribution of TRPA1 as a Downstream Signal of Proteinase-Activated Receptor-2 to Pancreatic Pain

Contribution of TRPA1 as a Downstream Signal of Proteinase-Activated Receptor-2 to Pancreatic Pain

Tacrolimus Triggers Transient Receptor Potential Vanilloid-1-Dependent Relapse of Pancreatitis-Related Pain in Mice

Protease‐activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain

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