OBJECTIVES: The mechanism of pain in chronic pancreatitis (CP) has yet to be explored. Proteinase-activated receptor 2 (PAR2) plays a pronociceptive role in visceral pain. The study aimed to assess the expression of PAR2 in dorsal root ganglia (DRGs) and validate its role of thermal hyperalgesia in CP. METHODS: Chronic pancreatitis model was induced by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Abdominal hyperalgesia was measured by thermal withdrawal latencies. The expression of PAR2 and transient receptor potential vanilloid 1 (TRPV1) were analyzed by immunofluorescence and Western blot. The messenger RNA encoding PAR2 was quantitated by real-time polymerase chain reaction. The effects of short-term and long-term ulinastatin treatment on abdominal thermal hyperalgesia of rats with CP were measured. RESULTS: Rats with CP showed a decreased thermal withdrawal latency. Proteinase-activated receptor 2 and TRPV1 were significantly upregulated in DRGs. The increased PAR2 protein expression was tightly correlated with thermal withdrawal latencies and TRPV1 expression. Short-term ulinastatin treatment inhibited the development of thermal hyperalgesia of rats with CP in a dose-dependent manner. CONCLUSIONS: The thermal hyperalgesia in CP is associated with an up-regulation of the PAR2 in DRGs. Proteinase-activated receptor 2 was involved in the pain generation in rats with CP.
OBJECTIVES: The mechanism of pain in chronic pancreatitis (CP) has yet to be explored. Proteinase-activated receptor 2 (PAR2) plays a pronociceptive role in visceral pain. The study aimed to assess the expression of PAR2 in dorsal root ganglia (DRGs) and validate its role of thermal hyperalgesia in CP. METHODS: Chronic pancreatitis model was induced by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Abdominal hyperalgesia was measured by thermal withdrawal latencies. The expression of PAR2 and transient receptor potential vanilloid 1 (TRPV1) were analyzed by immunofluorescence and Western blot. The messenger RNA encoding PAR2 was quantitated by real-time polymerase chain reaction. The effects of short-term and long-term ulinastatin treatment on abdominal thermal hyperalgesia of rats with CP were measured. RESULTS:Rats with CP showed a decreased thermal withdrawal latency. Proteinase-activated receptor 2 and TRPV1 were significantly upregulated in DRGs. The increased PAR2 protein expression was tightly correlated with thermal withdrawal latencies and TRPV1 expression. Short-term ulinastatin treatment inhibited the development of thermal hyperalgesia of rats with CP in a dose-dependent manner. CONCLUSIONS: The thermal hyperalgesia in CP is associated with an up-regulation of the PAR2 in DRGs. Proteinase-activated receptor 2 was involved in the pain generation in rats with CP.
Authors: Shayne N Hassler; Moeno Kume; Juliet M Mwirigi; Ayesha Ahmad; Stephanie Shiers; Andi Wangzhou; Pradipta R Ray; Serge N Belugin; Dhananjay K Naik; Michael D Burton; Josef Vagner; Scott Boitano; Armen N Akopian; Gregory Dussor; Theodore J Price Journal: JCI Insight Date: 2020-06-04
Authors: Dipti V Tillu; Shayne N Hassler; Carolina C Burgos-Vega; Tammie L Quinn; Robert E Sorge; Gregory Dussor; Scott Boitano; Josef Vagner; Theodore J Price Journal: Pain Date: 2015-05 Impact factor: 7.926
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