Transforming growth factor-beta1 impairs neuropathic pain through pleiotropic effects.
Transforming growth factor-beta1 impairs neuropathic pain through pleiotropic effects.
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DOI：
10.1186/1744-8069-5-16
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发表时间：
2009-03-27
期刊：
影响因子：
3.3
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Echeverry S;Shi XQ;Haw A;Liu H;Zhang ZW;Zhang J
了解周围神经系统损伤引起的神经病理性疼痛的潜在机制仍然具有挑战性，并可能导致显着改进的治疗方法。动态平衡的紊乱不仅发生在损伤部位，而且还延伸到脊髓和脑，涉及到各种类型的细胞。新的数据表明，神经免疫相互作用在慢性疼痛超敏反应的启动和维持中起作用。在这项研究中，我们试图研究转化生长因子-β1，一种有效的抗炎细胞因子，在减轻神经损伤诱导的神经病理性疼痛中的作用。通过建立神经病理性疼痛动物模型(部分结扎坐骨神经)，我们证明鞘内注射重组转化生长因子-β1可显著减轻神经损伤引起的神经病理性疼痛。转化生长因子-β-1治疗不仅可以防止神经损伤后神经病理性疼痛的发展，而且还可以逆转以前确立的神经病理性疼痛状况。在此背景下，转化生长因子-β1的生物学结果归因于其多效性作用。它能抑制周围神经损伤诱导的脊髓小胶质细胞、脊髓小胶质细胞和星形胶质细胞的激活，并通过阻止神经结扎后ATF3+神经元的诱导，从而减少受损神经元中趋化因子MCP-1的表达，显示出强大的神经保护作用。转化生长因子-β-1治疗也抑制神经损伤引起的脊髓炎症反应，细胞因子的表达减少。我们的研究结果表明，转化生长因子-β-1通过同时靶向神经元和神经胶质细胞来治疗神经病理性疾病。我们认为，转化生长因子-β-1等对不同类型细胞具有多潜能作用的治疗剂可以协同作用，恢复局部脊髓微环境的动态平衡，从而有助于减轻神经病理性疼痛。
Understanding the underlying mechanisms of neuropathic pain caused by damage to the peripheral nervous system remains challenging and could lead to significantly improved therapies. Disturbance of homeostasis not only occurs at the site of injury but also extends to the spinal cord and brain involving various types of cells. Emerging data implicate neuroimmune interaction in the initiation and maintenance of chronic pain hypersensitivity. In this study, we sought to investigate the effects of TGF-β1, a potent anti-inflammatory cytokine, in alleviating nerve injury-induced neuropathic pain in rats. By using a well established neuropathic pain animal model (partial ligation of the sciatic nerve), we demonstrated that intrathecal infusion of recombinant TGF-β1 significantly attenuated nerve injury-induced neuropathic pain. TGF-β1 treatment not only prevents development of neuropathic pain following nerve injury, but also reverses previously established neuropathic pain conditions. The biological outcomes of TGF-β1 in this context are attributed to its pleiotropic effects. It inhibits peripheral nerve injury-induced spinal microgliosis, spinal microglial and astrocytic activation, and exhibits a powerful neuroprotective effect by preventing the induction of ATF3+ neurons following nerve ligation, consequently reducing the expression of chemokine MCP-1 in damaged neurons. TGF-β1 treatment also suppresses nerve injury-induced inflammatory response in the spinal cord, as revealed by a reduction in cytokine expression. Our findings revealed that TGF-β1 is effective in the treatment of neuropathic by targeting both neurons and glial cells. We suggest that therapeutic agents such as TGF-β1 having multipotent effects on different types of cells could work in synergy to regain homeostasis in local spinal cord microenvironments, therefore contributing to attenuate neuropathic pain.
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DOI：
10.1016/0736-5748(94)00061-7
发表时间：
1995-06-01
影响因子：
1.8
作者：
BENVENISTE, EN;TANG, LP;LAW, RM
通讯作者：
LAW, RM
影响因子：
5.3
作者：
Colburn, RW;Rickman, AJ;DeLeo, JA
通讯作者：
DeLeo, JA
影响因子：
3.3
作者：
MORGANTIKOSSMANN, MC;KOSSMANN, T;WAHL, SM
通讯作者：
WAHL, SM
影响因子：
25
作者：
Krieglstein, K;Richter, S;Unsicker, K
通讯作者：
Unsicker, K
影响因子：
4.7
作者：
Nesic, O;Lee, J;Perez-Polo, JR
通讯作者：
Perez-Polo, JR