Format

Send to

Choose Destination
Nat Commun. 2016 May 31;7:11697. doi: 10.1038/ncomms11697.

BK channels in microglia are required for morphine-induced hyperalgesia.

Author information

1
Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.
2
Department of Anesthesiology, National Defense Medical College, Tokorozawa 359-8513, Japan.
3
Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
4
Department of Molecular and Cellular Anatomy, Faculty of Health Promotional Sciences, Tokoha University, Hamamatsu, Shizuoka 431-2102, Japan.
5
Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo 187-8502, Japan.
6
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
7
AMED-CREST, Japan Agency for Medical Research and Development, 1-7-1, Otemachi, Chiyoda-ku, Tokyo 100-004, Japan.

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 Ca(2+)-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.

PMID:
27241733
PMCID:
PMC4895018
DOI:
10.1038/ncomms11697
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center