Frontiers in Molecular Neuroscience (Mar 2022)
The Slack Channel Deletion Causes Mechanical Pain Hypersensitivity in Mice
- Ye Liu,
- Ye Liu,
- Ye Liu,
- Fang-Fang Zhang,
- Fang-Fang Zhang,
- Fang-Fang Zhang,
- Ying Song,
- Ying Song,
- Ying Song,
- Ran Wang,
- Ran Wang,
- Qi Zhang,
- Qi Zhang,
- Qi Zhang,
- Zhong-Shan Shen,
- Zhong-Shan Shen,
- Zhong-Shan Shen,
- Fei-Fei Zhang,
- Fei-Fei Zhang,
- Fei-Fei Zhang,
- Dan-Ya Zhong,
- Dan-Ya Zhong,
- Dan-Ya Zhong,
- Xiao-Hui Wang,
- Xiao-Hui Wang,
- Xiao-Hui Wang,
- Qing Guo,
- Qing Guo,
- Qing Guo,
- Qiong-Yao Tang,
- Qiong-Yao Tang,
- Qiong-Yao Tang,
- Zhe Zhang,
- Zhe Zhang,
- Zhe Zhang
Affiliations
- Ye Liu
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Ye Liu
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Ye Liu
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Fang-Fang Zhang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Fang-Fang Zhang
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Fang-Fang Zhang
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Ying Song
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Ying Song
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Ying Song
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Ran Wang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Ran Wang
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Qi Zhang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Qi Zhang
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Qi Zhang
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Zhong-Shan Shen
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Zhong-Shan Shen
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Zhong-Shan Shen
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Fei-Fei Zhang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Fei-Fei Zhang
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Fei-Fei Zhang
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Dan-Ya Zhong
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Dan-Ya Zhong
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Dan-Ya Zhong
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Xiao-Hui Wang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Xiao-Hui Wang
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Xiao-Hui Wang
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Qing Guo
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Qing Guo
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Qing Guo
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Qiong-Yao Tang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Qiong-Yao Tang
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Qiong-Yao Tang
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- Zhe Zhang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
- Zhe Zhang
- Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
- Zhe Zhang
- NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China
- DOI
- https://doi.org/10.3389/fnmol.2022.811441
- Journal volume & issue
-
Vol. 15
Abstract
The role of the Slack (also known as Slo2.2, KNa1.1, or KCNT1) channel in pain-sensing is still in debate on which kind of pain it regulates. In the present study, we found that the Slack–/– mice exhibited decreased mechanical pain threshold but normal heat and cold pain sensitivity. Subsequently, X-gal staining, in situ hybridization, and immunofluorescence staining revealed high expression of the Slack channel in Isolectin B4 positive (IB4+) neurons in the dorsal root ganglion (DRG) and somatostatin-positive (SOM+) neurons in the spinal cord. Patch-clamp recordings indicated the firing frequency was increased in both small neurons in DRG and spinal SOM+ neurons in the Slack–/– mice whereas no obvious slow afterhyperpolarization was observed in both WT mice and Slack–/– mice. Furthermore, we found Kcnt1 gene expression in spinal SOM+ neurons in Slack–/– mice partially relieved the mechanical pain hypersensitivity of Slack–/– mice and decreased AP firing rates of the spinal SOM+ neurons. Finally, deletion of the Slack channel in spinal SOM+ neurons is sufficient to result in mechanical pain hypersensitivity in mice. In summary, our results suggest the important role of the Slack channel in the regulation of mechanical pain-sensing both in small neurons in DRG and SOM+ neurons in the spinal dorsal horn.
Keywords
