Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury.
Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury.
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DOI：
10.1016/j.celrep.2015.09.080
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发表时间：
2015-11-10
期刊：
影响因子：
8.8
通讯作者：
Sharif-Naeini R
中科院分区：
文献类型：
--
作者：
Petitjean H;Pawlowski SA;Fraine SL;Sharif B;Hamad D;Fatima T;Berg J;Brown CM;Jan LY;Ribeiro-da-Silva A;Braz JM;Basbaum AI;Sharif-Naeini R
神经性疼痛是一种慢性衰弱性疾病，由神经损伤引起，在损伤消退后持续很长时间，其特征在于自发性疼痛和机械超敏反应。虽然脊髓背角抑制性张力的丧失是神经性疼痛的主要原因，但这种去抑制的分子和细胞机制尚不清楚。在这里，我们结合小鼠的药物遗传学激活和选择性消融方法，以确定脊髓小白蛋白（PV）表达抑制性中间神经元在幼稚和神经性疼痛条件下的贡献。未处理小鼠PV神经元通过PKCγ兴奋性中间神经元的去抑制产生神经病理性疼痛样机械异常性疼痛。相反，在神经损伤的小鼠中激活PV神经元会加重机械超敏反应。这些研究结果表明，PV中间神经元是模态特定的过滤器，门机械，但不是热输入到背角，增加PV中间神经元的活动可以改善机械超敏反应，神经损伤后发展。改善神经性疼痛的治疗需要更好地了解健康和疾病中处理外周感觉输入的脊髓神经元网络。Petitjean等人发现，含有标记物小清蛋白（PV）的抑制性中间神经元的子集阻止触摸输入激活疼痛回路。在神经损伤后，这些突触的数量减少，轻轻的触摸可以引起疼痛。
Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV inter-neuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury. Improved therapy for neuropathic pain requires a better understanding of the spinal cord neuronal networks that process peripheral sensory inputs in health and disease. Petitjean et al. find that a subset of inhibitory interneurons, containing the marker parvalbumin (PV), prevent touch inputs from activating pain circuits. After nerve injury, a decrease is seen in the number of these synapses, and light touch can elicit pain.
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影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
DOI：
10.1523/jneurosci.6451-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cavanaugh DJ;Chesler AT;Jackson AC;Sigal YM;Yamanaka H;Grant R;O'Donnell D;Nicoll RA;Shah NM;Julius D;Basbaum AI
通讯作者：
Basbaum AI
影响因子：
5.3
作者：
Cordero-Erausquin, M;Coull, JAM;De Koninck, Y
通讯作者：
De Koninck, Y
影响因子：
16.2
作者：
Kardon AP;Polgár E;Hachisuka J;Snyder LM;Cameron D;Savage S;Cai X;Karnup S;Fan CR;Hemenway GM;Bernard CS;Schwartz ES;Nagase H;Schwarzer C;Watanabe M;Furuta T;Kaneko T;Koerber HR;Todd AJ;Ross SE
通讯作者：
Ross SE
DOI：
10.1523/jneurosci.1299-11.2011
发表时间：
2011-07-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cavanaugh DJ;Chesler AT;Bráz JM;Shah NM;Julius D;Basbaum AI
通讯作者：
Basbaum AI