Anti-NGF treatment can reduce chronic neuropathic pain by changing peripheral mediators and brain activity in rats
Anti-NGF treatment can reduce chronic neuropathic pain by changing peripheral mediators and brain activity in rats
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DOI：
10.1097/fbp.0000000000000422
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发表时间：
2019-02-01
影响因子：
1.6
通讯作者：
Chacur, Marucia
中科院分区：
文献类型：
--
作者：
da Silva, Joyce T.;Evangelista, Bianca G.;Chacur, Marucia
神经性疼痛是由异常的外周和中枢处理驱动的，并且治疗不够有效。针对神经生长因子的抗体（抗-NGF）已被研究作为多种病症的有效镇痛治疗。然而，抗NGF在神经病理性疼痛中的外周和脑作用仍然未知。我们在大鼠坐骨神经压迫性损伤（CCI）模型中通过局部给药检查了抗NGF在减轻慢性疼痛中的有效性。检测背根神经节（DRG）和脊髓中的NGF和P物质。使用c-Fos在前扣带皮层和中脑导水管周围灰质腹外侧测量神经元激活。CCI后14天，抗NGF促进了机械阈值、热退缩潜伏期和冷敏感性的显著剂量依赖性改善，持续5 h。CCI后DRG和脊髓中的NGF上调被抗NGF降低，而P物质仅在DRG中增加，并且治疗降低了它。抗NGF诱导前扣带回皮质中神经元活化的显著减少，但在中脑导水管周围灰质腹外侧区中没有。这项研究首次证明了抗NGF对大脑活动的影响。因此，我们的研究结果表明，抗神经生长因子改善慢性神经性疼痛，直接作用于外周敏化和间接对中枢敏化。版权所有（c）2018威科医疗集团All rights reserved.
Neuropathic pain is driven by abnormal peripheral and central processing, and treatments are insufficiently effective. Antibodies against nerve growth factor (anti-NGF) have been investigated as a potent analgesic treatment for numerous conditions. However, the peripheral and brain effects of anti-NGF in neuropathic pain remain unknown. We examined the effectiveness of anti-NGF in reducing chronic pain by local administration in a rat model of sciatic constriction injury (CCI). NGF and substance P in the dorsal root ganglion (DRG) and spinal cord were evaluated. Neuronal activation was measured using c-Fos in the anterior cingulate cortex and ventrolateral periaqueductal gray. At 14 days after CCI, anti-NGF promoted a significant dose-dependent improvement in mechanical threshold, thermal withdrawal latency, and cold sensitivity, lasting for 5 h. NGF upregulation in the DRG and spinal cord after CCI was decreased by anti-NGF, while substance P was increased only in the DRG, and the treatment reduced it. Anti-NGF induced a significant reduction of neuronal activation in the anterior cingulate cortex, but not in the ventrolateral periaqueductal gray. This study provides the first evidence of the anti-NGF effects on brain activity. Thus, our findings suggest that anti-NGF improves chronic neuropathic pain, acting directly on peripheral sensitization and indirectly on central sensitization. Copyright (c) 2018 Wolters Kluwer Health, Inc. All rights reserved.