Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Pancreas. 2011 May;40(4):551-6. doi: 10.1097/MPA.0b013e318214fb77.
We examined the role of brain-derived neurotrophic factor (BDNF) in the pathogenesis of pain in an experimental model of chronic pancreatitis (CP).
Pancreatitis was induced by retrograde infusion of trinitrobenzene sulfonic acid into the pancreatic duct of adult rats. Twenty-one days after injection, BDNF expression was examined in pancreas-specific dorsal root ganglia (DRGs) by immunohistochemistry, and protein levels were quantified from DRGs and spinal cord extracts. The effects of intrathecal infusion of a neutralizing antibody to BDNF on pancreatic hyperalgesia were assessed by the sensitivity of the abdominal wall to filament probing as well as the nocifensive behavior to electrical stimulation of the pancreas.
Levels of BDNF in DRGs and spinal cords (T9-13) were significantly higher in trinitrobenzene sulfonic acid rats compared with controls, accompanied by an increase in the number of pancreas-specific neurons expressing BDNF immunoreactivity. Brain-derived neurotrophic factor antagonism suppressed phospho-tropomyosin-related kinase B receptor levels in the spinal cord and significantly reduced behavioral responses in rats with CP.
Brain-derived neurotrophic factor is upregulated in pancreas-specific primary afferent neurons in rats with CP, and BDNF antagonism is associated with a reduction of pain-related behavior in these animals, suggesting an important role for this neurotransmitter in the nociception of CP.
我们在慢性胰腺炎（CP）的实验模型中研究了脑源性神经营养因子（BDNF）在疼痛发病机制中的作用。
通过逆行向胰管内注入三硝基苯磺酸使成年大鼠产生胰腺炎。注射后 21 天，通过免疫组织化学法检查胰腺特异性背根神经节（DRG）中的 BDNF 表达，并从 DRG 和脊髓提取物中定量蛋白质水平。通过腹壁对纤维探测的敏感性以及对胰腺电刺激的伤害性行为来评估鞘内输注 BDNF 中和抗体对胰腺痛觉过敏的影响。
与对照组相比，三硝基苯磺酸大鼠的 DRG 和脊髓（T9-13）中的 BDNF 水平显着升高，同时表达 BDNF 免疫反应性的胰腺特异性神经元数量增加。BDNF 拮抗作用抑制了脊髓中磷酸化原肌球蛋白相关激酶 B 受体的水平，并显着减少了 CP 大鼠的行为反应。
CP 大鼠胰腺特异性初级传入神经元中 BDNF 上调，BDNF 拮抗作用与这些动物疼痛相关行为的减少有关，表明这种神经递质在 CP 的伤害感受中起重要作用。
