Acute Effects Of TGF-β1 And Possible Involvement In The Pain Of Chronic Pancreatitis In Rats

Background: Transforming growth factor beta1(TGFβ1) is upregulated in chronic inflammation, where it plays a key role in wound healing and promoting fibrosis. However, the role of TGFβ1 in nociceptive processing in primary sensory neurons remains unclear. The aim of this study is to investigate whether TGFβ1 plays a role in hyperalgesia in chronic pancreatitis(CP) and the underlying mechanisms.Methods: CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid(TNBS). Dil dye injected into pancreas was used to label pancreas-specific dorsal root ganglion(DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed to examine the effect of TGFβ1 on acutely isolated pancreas-specific DRG neurons(T9-T13). Western blot analysis was carried out to measure the expression of TGFβ1 and its receptors. Pancreatic hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation(VFF) of rat abdomen.Results:(1) TGFβ1 application induced depolarization of resting membrane potential and cause firing activity in pancreas-specific DRG neurons of health rats, which was more potentiated in CP rats.(2) Exposure to TGFβ1 in vitro increased neuronal excitability of DRG neurons from health rats.(3) TGFβ1 application increased the concentration of intracellular calcium in pancreas-specific DRG neurons of health rats, which was more potentiated in CP rats.(4) The expression of TGFβ1 in pancreas was significantly up-regulated in CP rats; the expression of TGFβ1 and it receptors in DRGs(T9-T13) were greatly up-regulated in CP rats.(5) Intrathecal injection of TGFβ1 induced abdominal hyperalgesia in health rats; intrathecal injection of TGFβ receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats.Conclusions: These results suggest that TGFβ1 can acutely excite primary sensory neurons and increase the concentration of intracellular calcium, which is activated and contributes to abdominal hyperalgesia in CP. This and future study would identify a potentially novel target for the treatment of abdominal hyperalgesia in CP.