Brudnick Neuropsychiatric Research Institute; Department of Neurobiology; Futai Lab
Neuroscience and Neurobiology
Voltage-gated potassium (Kv) channels are increasingly recognised as key regulators of nociceptive excitability. Kcns1 is one of the first potassium channels to be associated with neuronal hyperexcitability and mechanical sensitivity in the rat, as well as pain intensity and risk of developing chronic pain in humans. Here, we show that in mice, Kcns1 is predominantly expressed in the cell body and axons of myelinated sensory neurons positive for neurofilament-200, including Adelta-fiber nociceptors and low-threshold Abeta mechanoreceptors. In the spinal cord, Kcns1 was detected in laminae III to V of the dorsal horn where most sensory A fibers terminate, as well as large motoneurons of the ventral horn. To investigate Kcns1 function specifically in the periphery, we generated transgenic mice in which the gene is deleted in all sensory neurons but retained in the central nervous system. Kcns1 ablation resulted in a modest increase in basal mechanical pain, with no change in thermal pain processing. After neuropathic injury, Kcns1 KO mice exhibited exaggerated mechanical pain responses and hypersensitivity to both noxious and innocuous cold, consistent with increased A-fiber activity. Interestingly, Kcns1 deletion also improved locomotor performance in the rotarod test, indicative of augmented proprioceptive signalling. Our results suggest that restoring Kcns1 function in the periphery may be of some use in ameliorating mechanical and cold pain in chronic states.
Kv channels, Potassium channels, Kv9.1, Kcns1, Neuropathic pain, Peripheral neuropathy, Nerve injury
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Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI of Published Version
Pain. 2018 Aug;159(8):1641-1651. doi: 10.1097/j.pain.0000000000001255. Link to article on publisher's site
Tsantoulas, Christoforos; Denk, Franziska; Signore, Massimo; Nassar, Mohammed A.; Futai, Kensuke; and McMahon, Stephen B., "Mice lacking Kcns1 in peripheral neurons show increased basal and neuropathic pain sensitivity" (2018). Neurobiology Publications and Presentations. 230.
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This work is licensed under a Creative Commons Attribution 4.0 License.