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

• Published in: Neuroscience letters Vol. 589; pp. 200 - 206
• Main Authors: Koh, Keito, Hamada, Asami, Hamada, Yusuke, Yanase, Makoto, Sakaki, Mamiko, Someya, Kazuki, Narita, Michiko, Kuzumaki, Naoko, Ikegami, Daigo, Sakai, Hiroyasu, Iseki, Masako, Inada, Eiichi, Narita, Minoru
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 04-03-2015
• Subjects: Adrenergic Neurons - metabolism; Animals; Channelrhodopsins; Electric Stimulation; Electroencephalography; Electromyography; Light; Locus coeruleus; Locus Coeruleus - metabolism; Locus Coeruleus - radiation effects; Male; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Neuralgia - complications; Neuralgia - metabolism; Neuralgia - physiopathology; Neuropathic pain; Noradrenergic neurons; Optogenetics; Prefrontal Cortex - metabolism; Prefrontal Cortex - radiation effects; Sciatic Nerve - injuries; Sleep disturbance; Sleep Wake Disorders - etiology; Sleep Wake Disorders - metabolism; Sleep Wake Disorders - physiopathology; Sleep disturbance; Noradrenergic neurons; Optogenetics; Locus coeruleus; Neuropathic pain
• DOI: 10.1016/j.neulet.2014.12.002
• EISSN: 1872-7972
• ISSN: 0304-3940

•Activation of LC noradrenergic neurons increases in wakefulness with decreased NREM.•Neuropathic pain increases the activity of LC–PFC noradrenergic neurons.•Activation of LC–PFC noradrenergic neurons facilitates sleep-to-wake transitions.
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.