Synthetic Secoisolariciresinol Diglucoside Attenuates Established Pain, Oxidative Stress and Neuroinflammation in a Rodent Model of Painful Radiculopathy.

Synthetic Secoisolariciresinol Diglucoside Attenuates Established Pain, Oxidative Stress and Neuroinflammation in a Rodent Model of Painful Radiculopathy.
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DOI:
10.3390/antiox9121209
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发表时间:
2020-11-30
期刊:
Antioxidants (Basel, Switzerland)
影响因子:
--
通讯作者:
Winkelstein BA
Winkelstein BA
中科院分区:
其他
文献类型:
--
作者:
Kartha S;Weisshaar CL;Pietrofesa RA;Christofidou-Solomidou M;Winkelstein BA

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痛性颈神经根病的特征是慢性神经炎症,降低内源性抗氧化反应,导致神经创伤后氧化应激和疼痛的发展。因此,促进抗氧化信号和减少氧化损伤的抗氧化剂,如第二异甘油醚二葡萄糖苷(SDG),也可能起到缓解疼痛的作用。这项研究调查了在疼痛的牙根压迫后反复全身应用合成SDG是否可以减少典型的明显疼痛、氧化应激和脊髓神经胶质细胞激活。于压迫后第1~3天给予SDG,第7天用氧化应激标记物8-羟基鸟苷(8-OHG)和硝基酪氨酸测定背根神经节(DRG)和脊髓氧化损伤程度。在压迫后第7天分别检测脊髓小胶质细胞和星形胶质细胞的激活情况。除了减轻疼痛,SDG治疗还减少了脊髓8-OHG和硝基酪氨酸,以及外周DRG中的8-OHG。此外,SDG通过降低星形胶质细胞的激活程度而不是小胶质细胞的激活来选择性地降低胶质细胞的激活。这些发现表明,合成SDG可能通过抑制疼痛损伤后形成的氧化应激和星形胶质细胞激活来减轻现有的神经根性疼痛,可能被认为是治疗痛性神经根病的有效药物。
Painful cervical radiculopathy is characterized by chronic neuroinflammation that lowers endogenous antioxidant responses leading to the development of oxidative stress and pain after neural trauma. Therefore, antioxidants such as secoisolariciresinol diglucoside (SDG), that promote antioxidant signaling and reduce oxidative damage may also provide pain relief. This study investigated if repeated systemic administration of synthetic SDG after a painful root compression reduces the established pain, oxidative stress and spinal glial activation that are typically evident. SDG was administered on days 1–3 after compression and the extent of oxidative damage in the dorsal root ganglia (DRG) and spinal cord was measured at day 7 using the oxidative stress markers 8-hydroxguanosine (8-OHG) and nitrotyrosine. Spinal microglial and astrocytic activation were also separately evaluated at day 7 after compression. In addition to reducing pain, SDG treatment reduced both spinal 8-OHG and nitrotyrosine, as well as peripheral 8-OHG in the DRG. Moreover, SDG selectively reduced glial activation by decreasing the extent of astrocytic but not microglial activation. These findings suggest that synthetic SDG may attenuate existing radicular pain by suppressing the oxidative stress and astrocytic activation that develop after painful injury, possibly identifying it as a potent therapeutic for painful radiculopathies.
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