Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch.
Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch.
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DOI：
10.1016/j.neuron.2015.02.028
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发表时间：
2015-03-18
期刊：
影响因子：
16.2
通讯作者：
Zeilhofer, Hanns Ulrich
中科院分区：
文献类型：
--
作者：
Foster, Edmund;Wildner, Hendrik;Tudeau, Laetitia;Haueter, Sabine;Ralvenius, William T.;Jegen, Monika;Johannssen, Helge;Hoesli, Ladina;Haenraets, Karen;Ghanem, Alexander;Conzelmann, Karl-Klaus;Boesl, Michael;Zeilhofer, Hanns Ulrich
疼痛的门控理论认为，脊髓背角的抑制性神经元对伤害性信号向更高脑区的传递施加关键控制。在这里，我们研究了这些神经元的甘氨酸能亚群如何有助于特定于模态的疼痛和瘙痒处理。我们产生了一个GlyT 2：：Cre转基因小鼠系适合病毒介导的逆行追踪研究和空间精确消融，沉默，和甘氨酸能神经元的激活。我们发现这些神经元主要从有髓鞘初级感觉神经元接收感觉输入，并且它们的局部毒素介导的消融或沉默诱导局部机械、热和冷痛觉过敏;自发退缩行为;以及针对相应皮肤区域的过度舔和咬。相反，相同神经元的局部药物遗传学激活减轻了神经性痛觉过敏和氯喹和组胺诱导的瘙痒。这些结果建立了脊髓背角的甘氨酸能神经元作为抑制性疼痛和瘙痒控制回路的关键要素。甘氨酸能背角神经元对疼痛和瘙痒进行节段性控制，它们的局部抑制引起痛觉过敏和自发性不适的迹象。局部激活可减轻急性疼痛、神经性痛觉过敏和化学性瘙痒。建立背角甘氨酸能神经元作为疼痛和瘙痒的脊髓门的关键元件。这些神经元的沉默和消融诱导局部痛觉过敏和自发性不适，而它们的激活加重疼痛和瘙痒。
The gate control theory of pain proposes that inhibitory neurons of the spinal dorsal horn exert critical control over the relay of nociceptive signals to higher brain areas. Here we investigated how the glycinergic subpopulation of these neurons contributes to modality-specific pain and itch processing. We generated a GlyT2::Cre transgenic mouse line suitable for virus-mediated retrograde tracing studies and for spatially precise ablation, silencing, and activation of glycinergic neurons. We found that these neurons receive sensory input mainly from myelinated primary sensory neurons and that their local toxin-mediated ablation or silencing induces localized mechanical, heat, and cold hyperalgesia; spontaneous flinching behavior; and excessive licking and biting directed toward the corresponding skin territory. Conversely, local pharmacogenetic activation of the same neurons alleviated neuropathic hyperalgesia and chloroquine- and histamine-induced itch. These results establish glycinergic neurons of the spinal dorsal horn as key elements of an inhibitory pain and itch control circuit. Glycinergic dorsal horn neurons exert segmental control over pain and itch Their local inhibition causes hyperalgesia and signs of spontaneous discomfort Local activation reduces acute pain, neuropathic hyperalgesia, and chemical itch Foster et al. establish dorsal horn glycinergic neurons as critical elements of a spinal gate for pain and itch. Silencing and ablation of these neurons induces local hyperalgesia and spontaneous discomfort, whereas their activation alleviates pain and itch.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
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
影响因子：
48
作者：
Buch, T;Heppner, FL;Waisman, A
通讯作者：
Waisman, A
影响因子：
3.3
作者：
Akiyama T;Carstens E
通讯作者：
Carstens E
影响因子：
3.3
作者：
Keller AF;Beggs S;Salter MW;De Koninck Y
通讯作者：
De Koninck Y