Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors
Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors
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DOI：
10.1523/jneurosci.3388-05.2006
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发表时间：
2006-01-25
影响因子：
5.3
通讯作者：
Lawson, SN
中科院分区：
文献类型：
--
作者：
Djouhri, L;Koutsikou, S;Lawson, SN
自发性疼痛是人类神经性疼痛的一个知之甚少的方面，在动物中表现为自发性抬足（SFL）。为了确定SFL是否是由伤害性神经元自发放电引起的，我们研究了以下几组大鼠：（1）未治疗组;（2）脊髓神经轴突切断（SNA），L5 SNA 1周前;（3）mSNA，（改良SNA）、SNA+邻近L4脊神经松结扎加炎症诱导铬肠线;（4）CFA（完全弗氏佐剂），皮内注射完全弗氏佐剂诱导的后肢炎性反应分别提前1 d和4 d。在所有组中，记录SFL和同侧背根神经节（DRG）神经元（细胞内）的自发活动（SA）。在神经损伤（SNA/mSNA）组中测量诱发痛行为。在SNA和mSNA中，在完整的L4而不是轴突切断的L5 DRG中，SA增加了伤害感受型C-纤维神经元（C-伤害感受器）的数量（至35%），并且在CFA后1 - 4天的L4/L5 DRG中（至38 - 25%）。SFL发生在mSNA中，而不是SNA大鼠。它与机械性异常性疼痛、L4纤维损伤程度[ATF 3（激活转录因子3）免疫染色]或SA的L4 C-伤害感受器百分比无关。然而，具有SA的L4 C-伤害感受器在mSNA（1.8 Hz）后比SNA（0.02 Hz）更快地放电;估计的L4总放电率分别类似于5.0和类似于0.6 kHz。类似地，CFA后，1天后L4 C-伤害性感受器SA加快与SFL相关，而4天后SA减慢则与SFL无关。因此，炎症引起L4 C-伤害感受器SA和SFL。总体而言，SFL与完整C-伤害感受器的SA率相关。L5变性和铬肠都会引起炎症。因此，SA和SFL/神经损伤后自发性疼痛（mSNA）可能是累积性神经炎症所致。
Spontaneous pain, a poorly understood aspect of human neuropathic pain, is indicated in animals by spontaneous foot lifting (SFL). To determine whether SFL is caused by spontaneous firing in nociceptive neurons, we studied the following groups of rats: (1) untreated; (2) spinal nerve axotomy (SNA), L5SNA1 week earlier; (3) mSNA(modified SNA), SNAplus loose ligation of the adjacent L4 spinal nerve with inflammation-inducing chromic gut; and (4) CFA (complete Freund's adjuvant), intradermal complete Freund's adjuvant-induced hindlimb inflammation 1 and 4 d earlier. In all groups, recordings of SFL and of spontaneous activity (SA) in ipsilateral dorsal root ganglion (DRG) neurons (intracellularly) were made. Evoked pain behaviors were measured in nerve injury (SNA/mSNA) groups. Percentages of nociceptive-type C-fiber neurons (C-nociceptors) with SA increased in intact L4 but not axotomized L5 DRGs in SNA and mSNA (to 35%), and in L4/L5 DRGs 1 - 4 d after CFA (to 38 - 25%). SFL occurred in mSNA but not SNA rats. It was not correlated with mechanical allodynia, extent of L4 fiber damage [ATF3 (activation transcription factor 3) immunostaining], or percentage of L4 C-nociceptors with SA. However, L4 C-nociceptors with SA fired faster after mSNA (1.8 Hz) than SNA (0.02 Hz); estimated L4 total firing rates were similar to 5.0 and similar to 0.6 kHz, respectively. Similarly, after CFA, faster L4 C-nociceptor SA after 1 d was associated with SFL, whereas slower SA after 4 d was not. Thus, inflammation causes L4 C-nociceptor SA and SFL. Overall, SFL was related to SA rate in intact C-nociceptors. Both L5 degeneration and chromic gut cause inflammation. Therefore, both SA and SFL/spontaneous pain after nerve injury (mSNA) may result from cumulative neuroinflammation.