阻断Pannexin 1通道可以缓解周围炎症疼痛,但不能缓解帕克利塔塞尔诱导的神经病变
Julia Borges Paes Lemes1, Kaue Franco Malange1, Nathalia Santos Carvalho1
1Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil.
Journal of integrative neuroscience
|March 27, 2024
概括
Pannexin1 (Panx1) 在外周炎性疼痛和急性痛感中起着关键作用. 在背部根中阻断Panx1可降低疼痛敏感性,但对于慢性神经病痛来说并不必不可少.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 疼痛研究 疼痛研究
背景情况:
- 泛素1 (Panx1) 是一种道蛋白,与疼痛和炎症有关.
- 它在中枢神经系统疼痛中的作用是已知的,但其在外围神经元敏感化中的功能仍然不清楚.
- 背部根腺 (DRG) 对于疼痛处理至关重要,使其分子机制成为疼痛治疗的目标.
研究的目的:
- 研究Panx1在急性痛感和周围炎症和神经病痛中的作用.
- 探索Panx1在DRG神经元敏感化中的参与.
- 通过药理阻断和遗传淘汰模型评估Pax1对疼痛发展的贡献.
主要方法:
- 在L5-DRG中,老鼠接受了Panx1阻断剂 (10Panx),随后是炎症刺激物 (红素,甲素,素).
- 预先用10Panx对DRG神经元进行治疗,并用素刺激,以测量流入.
- 潘克斯1淘汰赛 (Panx1-KO) 鼠和野生型 (WT) 鼠被用卡拉基,素或帕克利塔塞尔治疗,通过弗雷测试评估了机械值.
主要成果:
- 鼠类DRG中Pax1阻断剂量依赖性降低了卡拉基安诱导的全音和甲诱导的恶感.
- 素诱导的疼痛和流量在受Panx1-阻断的老鼠和Panx1-KO小鼠中显著降低.
- 帕克利塔塞尔在WT中引起了急性疼痛,但不是Pax1-KO小鼠;慢性疼痛在两者中都发生,但最初在Pax1-KO小鼠中不那么严重.
结论:
- Panx1对于涉及TRPV1.1的周边炎症性疼痛和急性痛感至关重要.
- Panx1对于神经病痛的慢性性来说并不重要.
- 在DRG中准Panx1可能为炎症和急性疼痛条件提供治疗潜力.
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