{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:02:17Z","timestamp":1790622137377,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001528","name":"Wellington Medical Research Foundation","doi-asserted-by":"publisher","award":["2014\/241"],"award-info":[{"award-number":["2014\/241"]}],"id":[{"id":"10.13039\/501100001528","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001538","name":"Victoria University of Wellington","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001538","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>N<\/jats:italic>\u2010docosahexaenoyl ethanolamine (DHEA; also known as synaptamide) binds to both the cannabinoid\u20101 and 2 (CB1 and CB2) cannabinoid receptors and has anti\u2010inflammatory properties in vitro. However, the in vivo effects of DHEA remain unknown. Therefore, this study was designed to understand the effects of DHEA in models of pain and inflammation in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The intraplantar formaldehyde assay, hot water tail withdrawal assay and hotplate model were used to assess the antinociceptive properties of DHEA in mice. The mechanism of action was studied by antagonising the cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1) ion channel, peroxisome proliferator\u2010activated receptors (PPARs) and G\u2010protein receptor 55 (GPR55).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>N<\/jats:italic>\u2010docosahexaenoyl ethanolamine (2\u201310\u00a0mg\/kg) reduced the levels of nociceptive and inflammatory pain\u2010related behaviour over 60\u00a0min in the intraplantar formaldehyde assay via both intraperitoneal and local intraplantar administration. The area under the curve analysis showed the overall antinociceptive effects of DHEA (10\u00a0mg\/kg) were not modulated by pre\u2010treatment with antagonists for the cannabinoid receptors, TRPV1ion channel, PPAR\u03b1, PPAR\u03b3 or GPR55. However, the time\u2010course analysis showed that within the early inflammatory phase, antagonism of the CB2 receptor, PPAR\u03b1 and PPAR\u03b3 led to a partial reversal of the antinociceptive effects of DHEA. In the hot water tail withdrawal and hotplate models of thermal nociception, DHEA (2\u201310\u00a0mg\/kg) did not have any antinociceptive effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>N<\/jats:italic>\u2010docosahexaenoyl ethanolamine reduced the level of formaldehyde\u2010induced nociceptive and inflammatory pain\u2010related behaviour; however, was not active in thermal nociceptive models. This study highlights the potential of DHEA for the treatment of acute inflammatory pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study shows that both intraperitoneal and intraplantar administration of DHEA reduces the level of formaldehyde\u2010induced nociceptive and inflammatory pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1641","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T17:58:13Z","timestamp":1599069493000},"page":"1990-1998","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<i>N<\/i>\u2010docosahexaenoyl ethanolamine (synaptamide) has antinociceptive effects in male mice"],"prefix":"10.1002","volume":"24","author":[{"given":"Kelly F.","family":"Paton","sequence":"first","affiliation":[{"name":"School of Biological Sciences Centre for Biodiscovery Victoria University of Wellington Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahau","family":"Shirazi","sequence":"additional","affiliation":[{"name":"Callaghan Innovation Lower Hutt New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Vyssotski","sequence":"additional","affiliation":[{"name":"Callaghan Innovation Lower Hutt New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwyn M.","family":"Kivell","sequence":"additional","affiliation":[{"name":"School of Biological Sciences Centre for Biodiscovery Victoria University of Wellington Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1746-6148-10-21","article-title":"Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis","volume":"10","author":"Abramo F.","year":"2014","journal-title":"BMC Veterinary Research"},{"issue":"10","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.bbalip.2010.06.006","article-title":"Docosahexaenoic acid and eicosapentaenoic acid are converted by 3T3\u2010L1 adipocytes to N\u2010acyl ethanolamines with anti\u2010inflammatory properties","volume":"1801","author":"Balvers M. 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