Dissecting the mechanism of sensory neuron sensitization for the treatment of chronic pain

辣椒素受体vr1及其同源物VRL-1是表达初级传入神经元介导有害热刺激的阳离子通道。为了专门研究它们对初级传入神经敏化的作用，我们进行了以下实验。1)炎症后VR-1和VRL-1的组织化学分析我们对大鼠DRG进行了针对VR-1/VRL-1的免疫组织化学。我们测量了表达VR-1或VRL-1的初级传入神经元的数量。1.2)神经营养因子、NGF和GDNF在背根神经节（DRG）内的含量测定采用ELISA法测定DRG内NGF和GDNF的水平。这两种水平都因炎症而升高。3)抗ngf或抗gdnf对炎症后VR-1/VRL-1表达及行为痛觉过敏的影响。抗ngf和抗gdnf预处理可预防炎症引起的热痛觉过敏。用这两种因子治疗可抑制炎性VR-1表达，但不能抑制VRL-1。上述结果提示，诱导VR-1/VRL-1可促进炎症引起的热痛觉过敏。神经营养因子调节炎性VR-1表达，但不调节VRL-1表达。

Capsaicin Receptor, VR-1 and its homologue VRL-1 are cation channels and expressed primary afferent neurons to mediate noxious thermal stimulation. To specialize their role for the sensitization of primary afferent, we conducted some experiments as follows.1)Histochemical analysis of VR-1 and VRL-1 following inflammationWe performed immunohistochemistry against VR-1/VRL-1 in rat DRG. We measured the number of primary afferent neurons that express VR-1 or VRL-1. Peripheral inflammation increased expressions of both VR-1 and VRL-1.2)Measurement of neurotrophic factor, NGF and GDNF within the dorsal root ganglion(DRG)We determined the level of NGF and GDNF within the DRG by ELISA. Both level increased by the inflammation.3)Effect of anti-NGF or anti-GDNF on the expression of VR-1/VRL-1 as well as behavioural hyperalgesia following inflammation.Pre-treated with anti-NGF and anti-GDNF can prevent development of thermal hyperalgesia induced by the inflammation. Treatment with both factor inhibited inflammatory VR-1 expression but not VRL-1.These results suggest that induction of VR-1/VRL-1 can facilitate heat hyperalgesia induced by the inflammation. Nerve trophic factor regulate inflammatory VR-1 expression but not VRL-1.