BK channels in microglia are required for morphine-induced hyperalgesia

Yoshinori Hayashi

Research output: Contribution to journalArticle

Abstract

Although morphine is a gold standard medication, long-term opioid use is associated with serious side effects, such as morphine-induced hyperalgesia (MIH) and anti-nociceptive tolerance. Microglia-to-neuron signalling is critically involved in pain hypersensitivity. However, molecules that control microglial cellular state under chronic morphine treatment remain unknown. Here we show that the microglia-specific subtype of Ca2+ -activated K+ (BK) channel is responsible for generation of MIH and anti-nociceptive tolerance. We find that, after chronic morphine administration, an increase in arachidonic acid levels through the μ-opioid receptors leads to the sole activation of microglial BK channels in the spinal cord. Silencing BK channel auxiliary β3 subunit significantly attenuates the generation of MIH and anti-nociceptive tolerance, and increases neurotransmission after chronic morphine administration. Therefore, microglia-specific BK channels contribute to the generation of MIH and anti-nociceptive tolerance.
Original languageEnglish
JournalNature Communications
Volume7
Issue number11697
DOIs
Publication statusPublished - May 31 2016

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morphine
Large-Conductance Calcium-Activated Potassium Channels
Hyperalgesia
Microglia
Morphine
Calcium-Activated Potassium Channels
spinal cord
pain
Opioid Receptors
neurons
Arachidonic Acid
Synaptic Transmission
Opioid Analgesics
Neurons
Spinal Cord
Hypersensitivity
Chemical activation
activation

Cite this

BK channels in microglia are required for morphine-induced hyperalgesia. / Hayashi, Yoshinori.

In: Nature Communications, Vol. 7, No. 11697, 31.05.2016.

Research output: Contribution to journalArticle

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