{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:38:23Z","timestamp":1793968703666,"version":"4.8.0"},"reference-count":137,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kobe Gakuin University","award":["18K08836"],"award-info":[{"award-number":["18K08836"]}]},{"name":"Kobe Gakuin University","award":["21K08983"],"award-info":[{"award-number":["21K08983"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["18K08836"],"award-info":[{"award-number":["18K08836"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["21K08983"],"award-info":[{"award-number":["21K08983"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Early life stress, such as child abuse and neglect, and psychosocial stress in adulthood are risk factors for psychiatric disorders, including depression and anxiety. Furthermore, exposure to these stresses affects the sensitivity to pain stimuli and is associated with the development of chronic pain. However, the mechanisms underlying the pathogenesis of stress-induced depression, anxiety, and pain control remain unclear. Endogenous opioid signaling is reportedly associated with analgesia, reward, addiction, and the regulation of stress responses and anxiety. Stress alters the expression of various opioid receptors in the central nervous system and sensitivity to opioid receptor agonists and antagonists. \u03bc-opioid receptor-deficient mice exhibit attachment disorders and autism-like behavioral expression patterns, while those with \u03b4-opioid receptor deficiency exhibit anxiety-like behavior. In contrast, deficiency and antagonists of the \u03ba-opioid receptor suppress the stress response. These findings strongly suggest that the expression and dysfunction of the endogenous opioid signaling pathways are involved in the pathogenesis of stress-induced psychiatric disorders and chronic pain. In this review, we summarize the latest basic and clinical research studies on the effects of endogenous opioid signaling on early-life stress, psychosocial stress-induced psychiatric disorders, and chronic pain.<\/jats:p>","DOI":"10.3390\/ijms241411713","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T01:52:35Z","timestamp":1689904355000},"page":"11713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Stress-Induced Changes in the Endogenous Opioid System Cause Dysfunction of Pain and Emotion Regulation"],"prefix":"10.3390","volume":"24","author":[{"given":"Kazuo","family":"Nakamoto","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Tokuyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e20154079","DOI":"10.1542\/peds.2015-4079","article-title":"Global Prevalence of Past-year Violence against Children: A Systematic Review and Minimum Estimates","volume":"137","author":"Hillis","year":"2016","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e839","DOI":"10.1097\/PR9.0000000000000839","article-title":"Adverse childhood experiences and chronic pain among children and adolescents in the United States","volume":"5","author":"Groenewald","year":"2020","journal-title":"Pain Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0140-6736(22)00821-2","article-title":"Complex post-traumatic stress disorder","volume":"400","author":"Maercker","year":"2022","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S1090-3801(02)00072-1","article-title":"Childhood adversities in patients with fibromyalgia and somatoform pain disorder","volume":"7","author":"Imbierowicz","year":"2003","journal-title":"Eur. 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