The targeting treatment for prevention and restoration in patients with neuro-degenerative disease

脊髓内神经胶质细胞的激活可能参与神经病理性疼痛的发生。然而，关于脑源性神经营养因子(BDNF)和丝裂原活化蛋白激酶(MAPKs)在慢性疼痛中的作用还知之甚少。虽然已有文献证明MAPK通路可通过外周机制增加疼痛敏感性，但本研究主要集中在MAPK的中枢机制，尤其是ERK。在本研究中，我们描述了神经胶质细胞的特征，并评估了在给予BDNF诱导剂4-甲基儿茶酚(4-MC)后，PERK和c-fos的免疫反应性，可以改变这些与慢性疼痛有关的紊乱。建立SD大鼠慢性压迫性损伤(CCI)模型和神经病理性疼痛模型，通过缩短对热刺激的缩爪潜伏期(PWL)来评估疼痛。CCI后慢性注射4-MC。第14天分别注射Trk-B受体抑制剂K252a或JNK-1抑制剂SP600125，以确定4-MC的镇痛作用是否被逆转。动物用4%多聚甲醛灌流，固定后进行免疫组织化学染色(c-fos，perk)。大鼠CCI后PWL持续下降。第14天，疼痛通路相关区域和情绪相关区域的PERK和c-fos表达增加。4-MC可降低PWL，这种作用可被K252a和SP600125逆转，但不能被小胶质细胞失活剂米诺环素逆转。这些结果表明，疼痛-情绪系统中与PERK相关的神经胶质细胞的紊乱是慢性疼痛的原因，神经营养因子相关化合物通过诱导BDNF的诱导和细胞反应的正常化来阻止细胞内异常信号传递，从而缓解慢性疼痛。

The neuro-glia activation in the spinal cord may mediate neuropathic pain. However, little is known about the roles of brain-derived neurotrophic factor (BDNF) and mitogen-activated protein kinase (MAPKs) in chronic pain. Although it is well documented that MAPK pathways can increase pain sensitivity via peripheral mechanisms, the present study focused on central mechanisms of MAPKs, especially ERK. In the present study, we characterized neuro-glia and evaluated pERK and c-FOS immunoreactivity after administration of 4-methylcatechol (4-MC), a BDNF inducer, can modify these derangements in relation to chronic pain. A chronic constriction injury (CCI) model as for neuropathic pain model was prepared in SD rats and pain was assessed by a reduction in paw withdrawal latency (PWL) to heat stimuli. 4-MC was injected chronically after CCI. On day 14, k252a (Trk-B receptor inhibitor) or SP600125 (JNK-1 inhibitor) was injected to determine if the analgesic effects of 4-MC could be reversed. The animals were perfused with 4% paraformaldehyde followed by fixation for immunohistochemistry (c-FOS, pERK). The rats showed a persistent decrease in PWL after CCI. On day 14, there was increase in pERK and c-FOS in regions related to pain pathways and regions associated with emotion. 4-MC reduced the decrease in PWL and this effect was reversed by k252a and SP600125, but not by minocyclin, microglial inactivator.These results suggest that the derangement of neuro-glia associated with pERK in pain-emotion system are responsible for chronic pain Neurotrophic factor related compound ameliorates chronic pain by preventing abnormal intracellular signaling via induction of BDNF and normalization of cell responses.