Reactive oxygen species affect spinal cell type-specific synaptic plasticity in a model of neuropathic pain.
Reactive oxygen species affect spinal cell type-specific synaptic plasticity in a model of neuropathic pain.
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活性氧影响神经病理性疼痛模型中脊髓细胞类型特异性突触可塑性。
DOI：
10.1097/j.pain.0000000000001014
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发表时间：
2017-11
期刊：
影响因子：
7.4
通讯作者：
Chung JM
中科院分区：
文献类型：
--
作者：
Bittar A;Jun J;La JH;Wang J;Leem JW;Chung JM
脊髓突触可塑性被认为驱动中枢致敏，中枢致敏是神经性疼痛持续性的基础。我们最近的数据表明，在背角的突触可塑性是细胞类型特异性的：强烈的传入刺激产生长时程增强（LTP）的兴奋性脊髓丘脑束神经元（STTn），而它产生长时程抑制（LTD）的抑制性GABA能中间神经元（GABAn）。此外，活性氧（ROS）被证明参与LTP在STTn（STTn-LTP）以及在LTD在GABan（GABan-LTD）。本研究探讨了两种重要的ROS-超氧阴离子[·O2]和羟基自由基[·OH]-在神经病理性机械性痛觉过敏和细胞类型特异性脊髓突触可塑性中的作用。[·O2]供体比[·OH]供体在幼稚小鼠中诱导更强的机械性痛觉过敏。在脊髓神经结扎（SNL）小鼠神经病理性疼痛模型中，[·O2]清除剂比[·OH]清除剂具有更强的抗痛觉过敏作用。此外，[·O2]清除剂通过条件刺激（CS）抑制STTn-LTP和GABan-LTD的诱导，并分别减轻SNL诱导的增强和抑制。此外，[·OH]清除剂选择性地抑制GABan-LTD的诱导和维持以及SNL诱导的抑郁。这些结果表明SNL小鼠的机械性痛觉过敏是STTn-LTP和GABan-LTD共同作用的结果，行为学结果与电生理结果一致，提示[·O2]介导STTn-LTP和GABan-LTD，而[·OH]主要参与GABan-LTD。
Spinal synaptic plasticity is believed to drive central sensitization that underlies the persistent nature of neuropathic pain. Our recent data showed that synaptic plasticity in the dorsal horn is cell type-specific: intense afferent stimulation produced long-term potentiation (LTP) in excitatory spinothalamic tract neurons (STTn), whereas it produced long-term depression (LTD) in inhibitory GABAergic interneurons (GABAn). In addition, reactive oxygen species (ROS) were shown to be involved in LTP in STTn (STTn-LTP) as well as in LTD in GABAn (GABAn-LTD). This study examined the roles of two biologically important ROS—superoxide [·O2] and hydroxyl radicals [·OH]—in neuropathic mechanical hyperalgesia and cell type-specific spinal synaptic plasticity. A [·O2] donor induced stronger mechanical hyperalgesia than a [·OH] donor in naïve mice. A [·O2] scavenger showed greater anti-hyperalgesic effect than [·OH] scavengers in the spinal nerve ligation (SNL) mouse model of neuropathic pain. Moreover, a [·O2] donor induced STTn-LTP and GABAn-LTD, but a [·OH] donor induced only GABAn-LTD. In addition, a [·O2] scavenger inhibited STTn-LTP and GABAn-LTD induction (via conditioning stimulus (CS)) in naïve mice and alleviated SNL-induced potentiation and depression, respectively. Also, [·OH] scavenger selectively inhibited GABAn-LTD induction and maintenance as well as SNL-induced depression. These results indicate that mechanical hyperalgesia in SNL mice is the result of the combination of STTn-LTP and GABAn-LTD. Behavioral outcomes compliment electrophysiological results which suggest that [·O2] mediates both STTn-LTP and GABAn-LTD, whereas [·OH] is involved primarily in GABAn-LTD.
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影响因子：
4.7
作者：
Gwak, Young S.;Hulsebosch, Claire E.
通讯作者：
Hulsebosch, Claire E.
影响因子：
--
作者：
Beckhauser TF;Francis-Oliveira J;De Pasquale R
通讯作者：
De Pasquale R
影响因子：
37.3
作者：
Lejeune D;Hasanuzzaman M;Pitcock A;Francis J;Sehgal I
通讯作者：
Sehgal I
影响因子：
7.4
作者：
Ikeda, H;Kusudo, K;Murase, K
通讯作者：
Murase, K
DOI：
10.1016/1056-8719(94)90087-6
发表时间：
1994-12-01
影响因子：
1.9
作者：
MESTRE, C;PELISSIER, T;ESCHALIER, A
通讯作者：
ESCHALIER, A