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首页> 外文期刊>Pain. >Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury
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Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury

机译：细胞周期抑制作用限制了脊髓损伤后神经性疼痛的发生和维持

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摘要

Chronic pain after spinal cord injury (SCI) may present as hyperalgesia, allodynia, and/or spontaneous pain and is often resistant to conventional pain medications. Identifying more effective interventions to manage SCI pain requires improved understanding of the pathophysiological mechanisms involved. Cell cycle activation (CCA) has been implicated as a key pathophysiological event following SCI. We have shown that early central or systemic administration of a cell cycle inhibitor reduces CCA, prevents glial changes, and limits SCI-induced hyperesthesia. Here, we compared the effects of early vs late treatment with the pancyclin-dependent kinase inhibitor flavopiridol on allodynia as well as spontaneous pain. Adult C57BL/6 male mice subjected to moderate SCI were treated with intraperitoneal injections of flavopiridol (1 mg/kg), daily for 7 days beginning either 3 hours or 5 weeks after injury. Mechanical/thermal allodynia was evaluated, as well as spontaneous pain using the mouse grimace scale (MGS). We show that sensitivity to mechanical and thermal stimulation, and locomotor dysfunction were significantly reduced by early flavopiridol treatment compared with vehicle-treated controls. Spinal cord injury caused robust and extended increases of MGS up to 3 weeks after trauma. Early administration of flavopiridol significantly shortened duration of MGS changes. Late flavopiridol intervention significantly limited hyperesthesia at 7 days after treatment, associated with reduced glial changes, but without effect on locomotion. Thus, our data suggest that cell cycle modulation may provide an effective therapeutic strategy to reduce hyperesthesia after SCI, with a prolonged therapeutic window.
机译：脊髓损伤（SCI）后的慢性疼痛可能表现为痛觉过敏，异常性疼痛和/或自发性疼痛，并且通常对常规镇痛药物有抵抗力。识别出更有效的干预措施来控制SCI疼痛需要更好地了解所涉及的病理生理机制。细胞周期激活（CCA）已被认为是SCI之后的关键病理生理事件。我们已经表明，早期的中央或全身给药的细胞周期抑制剂可降低CCA，防止神经胶质细胞改变并限制SCI引起的感觉异常。在这里，我们比较了泛环素依赖性激酶抑制剂黄酮哌啶醇对早期和晚期治疗对异常性疼痛和自发性疼痛的影响。从伤后3小时或5周开始，每天腹膜内注射黄酮哌啶醇（1 mg / kg）对成年SCI的成年C57BL / 6雄性小鼠进行7天治疗。机械/热异常性疼痛，以及使用小鼠鬼脸秤（MGS）评估自发性疼痛。我们显示，与载体治疗的对照相比，早期黄酮哌啶醇治疗可显着降低对机械和热刺激的敏感性以及运动功能障碍。脊髓损伤在受伤后3周内引起MGS的强劲而持久的增加。黄酮哌啶醇的早期给药显着缩短了MGS改变的持续时间。黄酮哌啶醇的后期干预在治疗后第7天显着限制了感觉亢进，与胶质变化减少相关，但对运动没有影响。因此，我们的数据表明，细胞周期调节可能会提供一种有效的治疗策略，以减轻SCI后的感觉异常，并延长治疗窗口。

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