Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury.
Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury.
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DOI：
10.1523/jneurosci.2428-10.2010
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发表时间：
2010-11-03
期刊：
影响因子：
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通讯作者：
Walters ET
中科院分区：
文献类型：
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作者：
Bedi SS;Yang Q;Crook RJ;Du J;Wu Z;Fishman HM;Grill RJ;Carlton SM;Walters ET
脊髓损伤（SCI）后慢性疼痛的潜在机制尚未完全了解。大多数关于SCI疼痛机制的研究都集中在与炎症和胶质细胞激活相关的脊髓和脊髓上水平疼痛通路内的神经元改变。这些事件也可能影响初级感觉神经元的中枢过程，在伤害感受器中触发过度兴奋状态和自发活动（SA），从而驱动行为超敏反应和疼痛。SCI可以敏化伤害感受器的外周纤维并促进外周SA，但这些效应是由周围组织的外在改变驱动的还是伤害感受器的内在改变，以及体内伤害感受器中是否发生类似的SA尚不清楚。我们发现，小DRG神经元大鼠（褐家鼠）接受胸脊髓损伤3 d - 8个月前，并记录1 d后解离表现出SA的发病率升高加上索马兴奋过度相比，未经处理和假治疗组。SA发生率在腰DRG神经元中最高（57%），在颈神经元中最低（28%），并且在8个月内未能下降。许多采样的SA神经元辣椒素敏感和/或绑定的伤害性标记物，isolectin B4。这种内在的SA状态与对损伤水平以下和以上部位的机械和热刺激的行为反应性增加相关。C和Aδ纤维的记录显示，SCI诱导的SA在体内神经元胞体内或胞体附近产生。SCI促进初级伤害感受器进入慢性过度兴奋-SA状态，这可能在某些形式的持续性疼痛中提供有用的治疗靶点。
Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs in nociceptors in vivo are unknown. We show that small DRG neurons from rats (Rattus norvegicus) receiving thoracic spinal injury 3 d – 8 mo earlier and recorded 1 d after dissociation exhibit an elevated incidence of SA coupled with soma hyperexcitability compared to untreated and sham-treated groups. SA incidence was greatest in lumbar DRG neurons (57%) and least in cervical neurons (28%), and failed to decline over 8 mo. Many sampled SA neurons were capsaicin sensitive and/or bound the nociceptive marker, isolectin B4. This intrinsic SA state was correlated with increased behavioral responsiveness to mechanical and thermal stimulation of sites below and above the injury level. Recordings from C and Aδ fibers revealed SCI-induced SA generated in or near the neurons’ somata in vivo. SCI promotes the entry of primary nociceptors into a chronic hyperexcitable-SA state that may provide a useful therapeutic target in some forms of persistent pain.