The T-Type Calcium Channel Cav3.2 in Somatostatin Interneurons in Spinal Dorsal Horn Participates in Mechanosensation and Mechanical Allodynia in Mice.
The T-Type Calcium Channel Cav3.2 in Somatostatin Interneurons in Spinal Dorsal Horn Participates in Mechanosensation and Mechanical Allodynia in Mice.
复制标题
脊髓背角生长抑素中间神经元t型钙通道Cav3.2参与小鼠机械感觉和机械异常性痛。
DOI：
10.3389/fncel.2022.875726
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发表时间：
2022
影响因子：
5.3
通讯作者：
Zhang, Ying
中科院分区：
文献类型：
--
作者：
Zhi, Yu-Ru;Cao, Feng;Su, Xiao-Jing;Gao, Shu-Wen;Zheng, Hao-Nan;Jiang, Jin-Yan;Su, Li;Liu, Jiao;Wang, Yun;Zhang, Yan;Zhang, Ying
关键词：
生长抑素阳性(SOM+)神经元被认为是脊髓背角兴奋性中间神经元参与机械性疼痛的关键类群之一。然而，它们在痛觉调制中作用的分子机制仍不清楚。在此，我们发现T型钙通道Cav3.2在脊髓SOM+中间神经元中高表达。在原位杂交研究中，观察到Cacna 1h(编码Cav3.2)与SOMtd番茄共定位。脊髓背角SOMtd番茄细胞的荧光激活细胞分选也证明了Cacna 1h在SOM+神经元中的高表达。在行为上，病毒介导的脊髓SOM+神经元中Cacna 1h的敲除降低了幼稚小鼠对光接触的敏感性和对有害机械刺激的反应性。此外，在完全弗氏佐剂诱导的炎性痛模型中，敲除脊髓SOM+神经元中的Cacna 1h可以减轻热痛觉过敏和动态异位痛觉，在保留神经损伤的神经病理性疼痛模型中，Cacna 1h的抑制可以减少动态和静态异常痛觉。从机制上讲，在脊髓SOM+神经元中，Cacna 1h击倒后，脊髓背角浅层内Aβ-eEPSC和Aβ-eAP神经元的百分比下降。综上所述，我们的结果证明了Cav3.2在基础条件下脊髓SOM+神经元的机械感觉和病理性疼痛条件下的机械痛觉超敏中起着至关重要的作用。这项工作揭示了SOM+神经元传递机械性疼痛的分子基础，并显示了Cav3.2除了其公认的外周作用外，还在脊髓水平的触觉和疼痛处理中发挥功能作用。
Somatostatin-positive (SOM+) neurons have been proposed as one of the key populations of excitatory interneurons in the spinal dorsal horn involved in mechanical pain. However, the molecular mechanism for their role in pain modulation remains unknown. Here, we showed that the T-type calcium channel Cav3.2 was highly expressed in spinal SOM+ interneurons. Colocalization of Cacna1h (which codes for Cav3.2) and SOMtdTomato was observed in the in situ hybridization studies. Fluorescence-activated cell sorting of SOMtdTomato cells in spinal dorsal horn also proved a high expression of Cacna1h in SOM+ neurons. Behaviorally, virus-mediated knockdown of Cacna1h in spinal SOM+ neurons reduced the sensitivity to light touch and responsiveness to noxious mechanical stimuli in naïve mice. Furthermore, knockdown of Cacna1h in spinal SOM+ neurons attenuated thermal hyperalgesia and dynamic allodynia in the complete Freund’s adjuvant-induced inflammatory pain model, and reduced both dynamic and static allodynia in a neuropathic pain model of spared nerve injury. Mechanistically, a decrease in the percentage of neurons with Aβ-eEPSCs and Aβ-eAPs in superficial dorsal horn was observed after Cacna1h knockdown in spinal SOM+ neurons. Altogether, our results proved a crucial role of Cav3.2 in spinal SOM+ neurons in mechanosensation under basal conditions and in mechanical allodynia under pathological pain conditions. This work reveals a molecular basis for SOM+ neurons in transmitting mechanical pain and shows a functional role of Cav3.2 in tactile and pain processing at the level of spinal cord in addition to its well-established peripheral role.
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影响因子：
16.2
作者：
Cui, Lian;Miao, Xuerong;Liang, Lingli;Abdus-Saboor, Ishmail;Olson, William;Fleming, Michael S.;Ma, Minghong;Tao, Yuan-Xiang;Luo, Wenqin
通讯作者：
Luo, Wenqin
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
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Ma Q
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影响因子：
4.8
作者：
Chen W;Chi YN;Kang XJ;Liu QY;Zhang HL;Li ZH;Zhao ZF;Yang Y;Su L;Cai J;Liao FF;Yi M;Wan Y;Liu FY
通讯作者：
Liu FY
影响因子：
5.3
作者：
Gomez, Kimberly;Calderon-Rivera, Aida;Felix, Ricardo
通讯作者：
Felix, Ricardo
影响因子：
81.5
作者：
Colloca, Luana;Ludman, Taylor;Raja, Srinivasa N.
通讯作者：
Raja, Srinivasa N.