Cell death in the superficial dorsal horn in a model of neuropathic pain

Cell death in the superficial dorsal horn in a model of neuropathic pain
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DOI:
10.1002/jnr.1062
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发表时间:
2001-04
影响因子:
4.2
通讯作者:
G. Whiteside;R. Munglani
G. Whiteside;R. Munglani
中科院分区:
医学3区
文献类型:
--
作者:
G. Whiteside;R. Munglani

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本研究的目的是调查成年大鼠坐骨神经慢性压迫性损伤(CCI)后脊髓背角细胞凋亡的发生,并将其与行为反应相关联。如下使用六组六只大鼠:1)CCI,2)CCI,3)MK 801 + CCI,4)轴突切断术,5)假手术,和6)未处理的。在手术后8天对第1组动物进行热痛觉过敏的行为测试,并处死,取出脊髓并冷冻。其余组在手术后14天接受了相同的手术。采用TUNEL技术和Hoechst双标记法对脊髓腰段进行冷冻切片,并研究凋亡细胞的发生率。CCI后8天,同侧爪出现痛觉过敏,与对侧爪、未处理动物和假手术动物相比,其在损伤后14天仍存在。预先给予MK-801可预防痛觉过敏的发生。CCI后8天和14天,与对侧、幼稚动物和假手术动物相比,同侧脊髓背角中存在大量凋亡细胞。MK-801预先给药可将CCI导致的细胞凋亡程度降低至对照动物中观察到的水平。这项研究表明,细胞凋亡作为CCI的结果,同时发生痛觉过敏。此外,MK-801可预防痛觉过敏的发生并降低凋亡细胞死亡的程度,这可能表明凋亡有助于痛觉过敏的启动/维持。神经科学杂志Res. 64:168-173,2001.© 2001 Wiley利斯公司
The aims of this study were to investigate the occurrence of apoptotic cell death in the dorsal horn of the adult rat spinal cord following chronic constriction injury (CCI) to the sciatic nerve and to correlate this with behavioural responses. Six groups of six rats were used as follows: 1) CCI, 2) CCI, 3) MK801 + CCI, 4) axotomy, 5) sham, and 6) naive. Group 1 animals were behaviourally tested for thermal hyperalgesia 8 days following surgery and sacrificed and the spinal cords removed and frozen. The rest of the groups underwent the same procedure 14 days following surgery. The lumbar region of the spinal cord was cryosectioned and the incidence of apoptotic cells investigated using the TUNEL technique plus Hoechst double labelling. By 8 days post‐CCI, hyperalgesia had developed in the ipsilateral paw, which was still present 14 days after the injury compared to the contralateral paw and naive and sham animals. Preemptive MK‐801 prevented the onset of hyperalgesia. Significant numbers of apoptotic cells were present in the ipsilateral dorsal horn of the spinal cord 8 and 14 days following CCI compared to the contralateral side and to naive and sham animals. Preemptive treatment with MK‐801 reduced the extent of apoptosis resulting from CCI to the level seen in control animals. This study demonstrates that cells undergo apoptosis as a result of CCI simultaneous with the occurrence of hyperalgesia. Furthermore, MK‐801 prevents the onset of hyperalgesia and reduces the extent of apoptotic cell death, suggesting, perhaps, that apoptosis contributes to the initiation/maintenance of hyperalgesia. J. Neurosci. Res. 64:168–173, 2001. © 2001 Wiley‐Liss, Inc.