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Neurosci Lett. 2015 Mar 4;589:200-6. doi: 10.1016/j.neulet.2014.12.002. Epub 2014 Dec 3.

Possible involvement of activated locus coeruleus-noradrenergic neurons in pain-related sleep disorders.

Author information

1
Department of Pharmacology, Hoshi University School of Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan; Department of Anesthesiology and Pain Medicine, Juntendo University School of Medicine, 2-1-1Hongou, Bunkyou-ku, Tokyo 113-8421, Japan.
2
Department of Pharmacology, Hoshi University School of Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
3
Department of Anesthesiology and Pain Medicine, Juntendo University School of Medicine, 2-1-1Hongou, Bunkyou-ku, Tokyo 113-8421, Japan.
4
Department of Pharmacology, Hoshi University School of Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan; Department of Anesthesiology and Pain Medicine, Juntendo University School of Medicine, 2-1-1Hongou, Bunkyou-ku, Tokyo 113-8421, Japan; Life Science Tokyo Advanced Research Center (L-StaR), 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: narita@hoshi.ac.jp.

Abstract

The locus coeruleus (LC) is a noradrenergic brainstem structure that is considered to play a role in promoting arousal. To further clarify the role of LC noradrenergic neurons, we performed an optogenetic assay by injecting AAV-channelrhodopsin-2 (ChR2) into the LC of cre-tyrosine hydrolase (TH) mice. We found here that the specific activation of LC noradrenergic neurons produced a significant increase in wakefulness and a significant decrease in non-rapid eye movement (NREM) sleep during photostimulation. On the other hand, neuropathic pain is believed to significantly interfere with sleep, and inadequate sleep may contribute to the stressful negative consequences of living with pain. In the present study, sciatic nerve ligation, which produced significant thermal hyperalgesia, significantly increased the levels of noradrenaline released in the prefrontal cortex (PFC) by the weak electrical stimulation of neurons in the LC. Under these conditions, the systemic administration of adrenaline α and β inhibitor cocktail at 7 days after sciatic nerve ligation restored the increased wakefulness and decreased NREM sleep to normal levels. These results suggest that neuropathic pain may accelerate neurons in the LC, and its overactivation may be, at least in part, associated with sleep disturbance under neuropathic pain.

KEYWORDS:

Locus coeruleus; Neuropathic pain; Noradrenergic neurons; Optogenetics; Sleep disturbance

PMID:
25481765
DOI:
10.1016/j.neulet.2014.12.002
[Indexed for MEDLINE]

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