{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T20:41:40Z","timestamp":1776372100893,"version":"3.51.2"},"reference-count":63,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetic peripheral neuropathy (DPN) is a complication of diabetes connected with morbidity and mortality. DPN presents deterioration of peripheral nerves with pain, feebleness, and loss of sensation. Particular medications might display their remedial potential by controlling neuroinflammation. Palmitoylethanolamide (PEA) is an autacoid local injury antagonist distinguished for its neuroprotective, analgesic, and anti\u2010inflammatory properties in numerous experimental models of neuroinflammation. Based on these findings, the goal of this work was to better test the neuroprotective effects of a formulation of micronized PEA (PEA\u2010m) and the probable mechanism of action in a mouse model of DPN induced by streptozotocin (STZ) injection. Diabetic and control animals received PEA\u2010m (10 mg\/kg) by oral gavage daily starting 2 wk from STZ injection. After 16 wk, the animals were euthanized, and blood, urine, spinal cord, and sciatic nerve tissues were collected. Our results demonstrated that after diabetes induction, PEA\u2010m was able to reduce mechanical, thermal hyperalgesia, and motor alterations as well as reduce mast cell activation and nerve growth factor expression. In addition, PEA\u2010m decreased neural histologic damage, oxidative and nitrosative stress, cytokine release, angiogenesis, and apoptosis. Moreover, spinal microglia activation (IBA\u20101), phospho\u2010P38 MAPK, and nuclear factor NF\u2010\u03baB inflammatory pathways were also inhibited. The protective effects of PEA\u2010m could be correlated at least in part to peroxisome proliferator\u2010activated receptor\u2010\u03b1 activation. In summary, we demonstrated that PEA\u2010m represents a new therapeutic strategy for neuroinflammation pain associated with mixed neuropathies.\u2014Impellizzeri, D., Peritore, A. F., Cordaro, M., Gugliandolo, E., Siracusa, R., Crupi, R., D'Amico, R., Fusco, R., Evangelista, M., Cuzzocrea, S., Di Paola, R. The neuroprotective effects of micronized PEA (PEA\u2010m) formulation on diabetic peripheral neuropathy in mice. FASEB J. 33, 11364\u201311380 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900538r","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T17:52:21Z","timestamp":1564077141000},"page":"11364-11380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["The neuroprotective effects of micronized PEA (PEA\u2010m) formulation on diabetic peripheral neuropathy in mice"],"prefix":"10.1096","volume":"33","author":[{"given":"Daniela","family":"Impellizzeri","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio Filippo","family":"Peritore","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marika","family":"Cordaro","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Gugliandolo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalba","family":"Siracusa","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalia","family":"Crupi","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramona","family":"D'Amico","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Fusco","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Institute of Anaesthesiology and Reanimation Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Cuzzocrea","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"},{"name":"Department of Pharmacological and Physiological Science Saint Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosanna","family":"Di Paola","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Science University of Messina Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ilt052"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/157339906776818569"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.4314\/tjpr.v13i9.8","article-title":"Ameliorative potential of morin in streptozotocin-induced neuropathic pain in rats","volume":"13","author":"AlSharari S. 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