TY - JOUR
T1 - BK channel in microglia as a potent therapeutic molecular target for neuropathic pain
AU - Hayashi, Yoshinori
AU - Nakanishi, Hiroshi
N1 - Funding Information:
This work was supported by the Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (H.N.), and Grants-in-Aid for Young Scientific Research (No. 24791979 to Y. H.) from the Ministry of Education, Science, and Culture Japan , and Takeda Science Foundation, Japan (Y.H.).
Publisher Copyright:
© 2015 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Background: Ketamine, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been used in the treatment of chronic neuropathic pain. However, serious troubles have still remained in ketamine for the clinical treatment because of the strong adverse side effects during the long-term use. S-ketamine, one of the ketamine enantiomers, has a potent analgesic effect and weak side effects compared with R-ketamine. To date, analgesic potency of S- and R-ketamine was not been fully accounted for in the binding affinity to NMDA receptors. In the present review, we provide a novel analgesic mechanism of ketamine on chronic pain. Highlight: Spinal microglia after nerve injury activate Ca2+-binding site of Ca2+-activated K+ (BK) channels. S-ketamine significantly inhibited BK channel activation in spinal microglia. Intrathecal administration of BK channel activator mimics allodynia-like behavior, which was completely inhibited by S-ketamine. BK channel inhibitor alleviated neuropathic pain. BK channel inhibitor suppressed microglial activation in the spinal dorsal horn. Conclusion: These findings suggest that potent analgesic effects of S-ketamine arise from the inhibition of microglial BK channels, in addition to neuronal NMDA receptors. Thus, BK channels in microglia are a potential target for the treating of neuropathic pain.
AB - Background: Ketamine, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been used in the treatment of chronic neuropathic pain. However, serious troubles have still remained in ketamine for the clinical treatment because of the strong adverse side effects during the long-term use. S-ketamine, one of the ketamine enantiomers, has a potent analgesic effect and weak side effects compared with R-ketamine. To date, analgesic potency of S- and R-ketamine was not been fully accounted for in the binding affinity to NMDA receptors. In the present review, we provide a novel analgesic mechanism of ketamine on chronic pain. Highlight: Spinal microglia after nerve injury activate Ca2+-binding site of Ca2+-activated K+ (BK) channels. S-ketamine significantly inhibited BK channel activation in spinal microglia. Intrathecal administration of BK channel activator mimics allodynia-like behavior, which was completely inhibited by S-ketamine. BK channel inhibitor alleviated neuropathic pain. BK channel inhibitor suppressed microglial activation in the spinal dorsal horn. Conclusion: These findings suggest that potent analgesic effects of S-ketamine arise from the inhibition of microglial BK channels, in addition to neuronal NMDA receptors. Thus, BK channels in microglia are a potential target for the treating of neuropathic pain.
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U2 - 10.1016/j.job.2015.03.001
DO - 10.1016/j.job.2015.03.001
M3 - Review article
AN - SCOPUS:84938739760
SN - 1349-0079
VL - 57
SP - 131
EP - 134
JO - journal of oral biosciences
JF - journal of oral biosciences
IS - 3
ER -