GFβ1对神经元兴奋性的急性作用及参与介导慢性胰腺炎大鼠的痛觉过敏

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). Pancreatic hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. 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. Results: Intrathecal injection of TGFβ receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGFβ1 application depolarized the membrane potential and caused firing activity of pancreas-specific DRG neurons. TGFβ1 application also reduced the rheobase, hyperpolarized action potential threshold and increased the number of action potentials evoked by current injection of pancreas-specific DRG neurons. TGFβ1 application increased the concentration of intracellular calcium of pancreas-specific DRG neurons, which was inhibited by TGFβ receptor I antagonist but not by TRPV1 receptor antagonist. Furthermore, intrathecal injection of TGFβ1 produced abdominal hyperalgesia in health rats. Conclusions: These results suggest that TGFβ1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGFβ receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for the treatment of abdominal pain in CP.