The Slack Channel Deletion Causes Mechanical Pain Hypersensitivity in Mice

The role of the Slack (also known as Slo2.2, K 1.1, 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...

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Published in:Frontiers in molecular neuroscience 2022-03, Vol.15, p.811441-811441
Main Authors: Liu, Ye, Zhang, Fang-Fang, Song, Ying, Wang, Ran, Zhang, Qi, Shen, Zhong-Shan, Zhang, Fei-Fei, Zhong, Dan-Ya, Wang, Xiao-Hui, Guo, Qing, Tang, Qiong-Yao, Zhang, Zhe
Format: Article
Language:English
Subjects:
Afterhyperpolarization
Behavior
Dorsal horn
Dorsal root ganglia
DRG neurons
Firing rate
Gene expression
Genomes
Hybridization
Hypersensitivity
Immunofluorescence
mechanical pain
Neurons
Neuroscience
Pain
Pain perception
potassium channel
Protein expression
Proteins
Rodents
Slack channel
SOM+ neurons
Somatostatin
Spinal cord
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Summary:The role of the Slack (also known as Slo2.2, K 1.1, 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, 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 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.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2022.811441