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- 대한소화관운동학회(현 대한소화기능성질환.운동학회) Journal of Neurogastroenterology and Motility (JNM) Journal of Neurogastroenterology and Motility (JNM) Vol.22 No.2
- 발행연도
- 2016.1
- 수록면
- 333 - 343 (11page)
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Background/AimsThis study was to investigate whether transforming growth factor-β1 (TGF-β1) plays a role in hyperalgesia in chronic pancreatitis (CP)and the underlying mechanisms. MethodsCP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia wasassessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Dil dye injected into the pancreas was used to labelpancreas-specific dorsal root ganglion (DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed toexamine the effect of TGF-β1 on acutely isolated pancreas-specific DRG neurons. Western blot analysis was carried out to measure theexpression of TGF-β1 and its receptors. ResultsTNBS injection significantly upregulated expression of TGF-β1 in the pancreas and DRGs, and TGF-β1 receptors in DRGs (T9-T13)in CP rats. Intrathecal injection of TGF-β receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGF-β1application depolarized the membrane potential and caused firing activity of DRG neurons. TGF-β1 application also reduced rheobase,hyperpolarized action potential threshold, and increased numbers of action potentials evoked by current injection of pancreas-specificDRG neurons. TGF-β1 application also increased the concentration of intracellular calcium of DRG neurons, which was inhibited bySB431542. Furthermore, intrathecal injection of TGF-β1 produced abdominal hyperalgesia in healthy rats. ConclusionsThese results suggest that TGF-β1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGF-β1and its receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for thetreatment of abdominal pain in CP.
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