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

辣椒素受体VR-1及其同系物VRL-1是阳离子通道，表达初级传入神经元，介导伤害性热刺激。1)炎症后VR-1和VRL-1的组织化学分析大鼠背根神经节内VR-1和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。(2)背根神经节(DRG)内神经营养因子、神经生长因子(NGF)和胶质细胞源性神经营养因子(GDNF)的表达：用双抗体夹心法测定背根神经节(DRG)内NGF和GDNF的表达。3)抗NGF或抗GDNF对炎症后VR-1/VRL-1表达及行为痛敏的影响，预先给予抗NGF和抗GDNF可预防炎症所致的热痛敏的发展。两种因子均可抑制炎性VRL-1的表达，但不抑制VRL-1的表达。提示VRL-1/VRL-1的诱导可促进炎症引起的热痛敏。神经营养因子调节炎症性VR-1的表达，但不调节VRL-1的表达。

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.