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As part of the skin neuroendocrine system, the opioid receptor system exemplifies the closeness between the nervous system and the skin. Overexpression of the <jats:italic>\u03b4<\/jats:italic>\u2010opioid receptor in keratinocytes yields dysregulation of involucrin, loricrin, and filaggrin, proteins essential to the integrity of the skin barrier. The <jats:italic>\u03bc<\/jats:italic>\u2010opioid receptor ligand <jats:italic>\u03b2<\/jats:italic>\u2010endorphin, produced in the pituitary gland and a variety of skin cells, promotes wound healing <jats:italic>via<\/jats:italic> regulation of cytokeratin 16 and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010<jats:italic>\u03b2<\/jats:italic> type <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> receptor expression in keratinocytes. These and other published results discussed in this viewpoint are evidence for the fundamental role of the skin opioid receptor system in skin homeostasis, regeneration and ageing. While considerable progress in understanding the opioid receptors\u2019 function on the cellular level has been made, there is a need to link these results to physiological observations for the development of local skin therapies.<\/jats:p>","DOI":"10.1111\/exd.13021","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T15:11:11Z","timestamp":1460301071000},"page":"586-591","source":"Crossref","is-referenced-by-count":32,"title":["Opioids and skin homeostasis, regeneration and ageing \u2013 What's the evidence?"],"prefix":"10.1111","volume":"25","author":[{"given":"Paul L.","family":"Bigliardi","sequence":"first","affiliation":[{"name":"YLL School of Medicine National University Singapore Singapore"},{"name":"Division of Rheumatology University Medicine Cluster National University Hospital Singapore"},{"name":"Experimental Dermatology Institute of Medical Biology Agency for Science Technology &amp; Research (A*STAR) Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Dancik","sequence":"additional","affiliation":[{"name":"Experimental Dermatology Institute of Medical Biology Agency for Science Technology &amp; Research (A*STAR) Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Neumann","sequence":"additional","affiliation":[{"name":"Experimental Dermatology Institute of Medical Biology Agency for Science Technology &amp; Research (A*STAR) Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Bigliardi\u2010Qi","sequence":"additional","affiliation":[{"name":"Experimental Dermatology Institute of Medical Biology Agency for Science Technology &amp; Research (A*STAR) Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,6,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-19683-6_1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.21.5.457"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.00844.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2007.01.007"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026043451618"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.370"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.4204"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01923606"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2014.11.027"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2007.08.002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701015"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12343712"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(96)00570-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1201\/b16573-19"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3619"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2013.813932"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-8716(98)00087-8"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.88.285"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.05.132"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700942"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000082563"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.09.010"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2013.12.223"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-1353"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/16.9.1953"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.297.6662.1501"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00801.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12018.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00280"},{"key":"e_1_2_9_31_1","first-page":"317","volume":"7","author":"Xue J Z","year":"1991","journal-title":"Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi"},{"key":"e_1_2_9_32_1","first-page":"641","volume":"104","author":"Wintzen M","year":"1995","journal-title":"J Invest Dermatol"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08667.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12223"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.2006.00065.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12687"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1986.tb07967.x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(84)90204-0"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1994.1085"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13042"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-005-6040-3"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2011.08.021"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-011-9314-5"},{"key":"e_1_2_9_44_1","volume-title":"Structure and Function of Aged Skin. 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