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They can be both a cause and a consequence of each other, and should therefore be simultaneously treated. However, optimal treatments for chronic pain-related sleep disorders are not well established. Here, we aimed to investigate the effects of suvorexant, a novel sleep drug, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, on pain-related changes in sleep parameters in a preclinical chronic pain mice model, by partial sciatic nerve ligation. We evaluated the quantity, duration, and depth of sleep by analyzing the electroencephalogram and voluntary activity by counting the number of wheel rotations to determine various symptoms of sleep disorders, including reduced total sleep time, fragmentation, low quality, and impaired activity in the daytime. Suvorexant and mirtazapine normalized the reduction in sleep time and fragmented sleep, further regaining the sleep depth at sleep onset in the chronic pain state in nerve-ligated mice. Mirtazapine also increased the percentage of rapid eye movement sleep in mice. Suvorexant decreased voluntary activity, which was prolonged after administration; however, mirtazapine did not decrease it. Although the effects of suvorexant and mirtazapine on sleep and activity are different, both suvorexant and mirtazapine could be potential therapeutic agents for chronic pain-related sleep disorders.<\/jats:p>","DOI":"10.1371\/journal.pone.0264386","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T18:47:07Z","timestamp":1645814827000},"page":"e0264386","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Suvorexant and mirtazapine improve chronic pain-related changes in parameters of sleep and voluntary physical performance in mice with sciatic nerve ligation"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8492-6550","authenticated-orcid":true,"given":"Hisakatsu","family":"Ito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tsuneki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyasu","family":"Sasaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Toyooka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuaki","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"pone.0264386.ref001","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1097\/j.pain.0000000000000160","article-title":"A classification of chronic pain for ICD-11","volume":"156","author":"RD Treede","year":"2015","journal-title":"Pain"},{"key":"pone.0264386.ref002","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1186\/1471-2458-11-770","article-title":"Pain as a global public health priority","volume":"11","author":"DS Goldberg","year":"2011","journal-title":"BMC Public Health"},{"key":"pone.0264386.ref003","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1185\/03007995.2010.545813","article-title":"Epidemiology of chronic non-cancer pain in Europe: Narrative review of prevalence, pain treatments and pain impact","volume":"27","author":"KJ Reid","year":"2011","journal-title":"Curr Med Res Opin"},{"key":"pone.0264386.ref004","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/2049463713493264","article-title":"Chronic pain epidemiology\u2014where do lifestyle factors fit in?","volume":"7","author":"O van Hecke","year":"2013","journal-title":"Br J Pain"},{"key":"pone.0264386.ref005","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/s00586-011-1954-8","article-title":"Erratum to: Prevalence of sleep disturbance in patients with low back pain","volume":"21","author":"SM Alsaadi","year":"2012","journal-title":"Eur Spine J"},{"key":"pone.0264386.ref006","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1155\/2014\/480859","article-title":"Major depressive disorder and sleep disturbance in patients with chronic pain","volume":"19","author":"PC Emery","year":"2014","journal-title":"Pain Res Manag"},{"key":"pone.0264386.ref007","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1111\/j.1526-4637.2011.01115.x","article-title":"Psychological flexibility may reduce insomnia in persons with chronic pain: a preliminary retrospective study","volume":"12","author":"LM McCracken","year":"2011","journal-title":"Pain Med"},{"key":"pone.0264386.ref008","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1111\/1756-185X.13713","article-title":"Fibromyalgia, sleep disturbance and menopause: is there a relationship? 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