BK channel in microglia as a potent therapeutic molecular target for neuropathic pain

Yoshinori Hayashi, Hiroshi Nakanishi

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
Pages (from-to)131-134
Number of pages4
Journaljournal of oral biosciences
Volume57
Issue number3
DOIs
Publication statusPublished - Aug 1 2015

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Large-Conductance Calcium-Activated Potassium Channels
Ketamine
Microglia
Neuralgia
Analgesics
N-Methyl-D-Aspartate Receptors
Therapeutics
Chronic Pain
Chemical activation
Calcium-Activated Potassium Channels
Enantiomers
Hyperalgesia
Binding Sites

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Dentistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

BK channel in microglia as a potent therapeutic molecular target for neuropathic pain. / Hayashi, Yoshinori; Nakanishi, Hiroshi.

In: journal of oral biosciences, Vol. 57, No. 3, 01.08.2015, p. 131-134.

Research output: Contribution to journalReview article

Hayashi, Yoshinori ; Nakanishi, Hiroshi. / BK channel in microglia as a potent therapeutic molecular target for neuropathic pain. In: journal of oral biosciences. 2015 ; Vol. 57, No. 3. pp. 131-134.
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