{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:07Z","timestamp":1788393607613,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T00:00:00Z","timestamp":1589500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Inflammation is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, damage to peripheral nerves can cause a loss of sensory function and produces persistent neuropathic pain. To date, various potential approaches for neuropathic pain have focused on controlling neuroinflammation. The aim of this study was to investigate the neuroprotective effects of a new association of ultramicronized Palmitoylethanolamide (PEAum), an Autacoid Local Injury Antagonist Amide (ALIAmide) with analgesic and anti-inflammatory properties, with Paracetamol, a common analgesic, in a rat model of sciatic nerve injury (SNI). The association of PEAum\u2013Paracetamol, in a low dose (5 mg\/kg + 30 mg\/kg), was given by oral gavage daily for 14 days after SNI. PEAum\u2013Paracetamol association was able to reduce hyperalgesia, mast cell activation, c-Fos and nerve growth factor (NGF) expression, neural histological damage, cytokine release, and apoptosis. Furthermore, the analgesic action of PEAum\u2013Paracetamol could act in a synergistic manner through the inhibition of the NF-\u03baB pathway, which leads to a decrease of cyclooxygenase 2-dependent prostaglandin E2 (COX-2\/PGE2) release. In conclusion, we demonstrated that PEAum associated with Paracetamol was able to relieve pain and neuroinflammation after SNI in a synergistic manner, and this therapeutic approach could be relevant to decrease the demand of analgesic drugs.<\/jats:p>","DOI":"10.3390\/ijms21103509","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T10:53:59Z","timestamp":1589540039000},"page":"3509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["RETRACTED: Ultramicronized Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat"],"prefix":"10.3390","volume":"21","author":[{"given":"Alessio","family":"Peritore","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-2505","authenticated-orcid":false,"given":"Rosalba","family":"Siracusa","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0223-1403","authenticated-orcid":false,"given":"Roberta","family":"Fusco","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-3154","authenticated-orcid":false,"given":"Enrico","family":"Gugliandolo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-3871","authenticated-orcid":false,"given":"Ramona","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-0043","authenticated-orcid":false,"given":"Marika","family":"Cordaro","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-3132","authenticated-orcid":false,"given":"Rosalia","family":"Crupi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Genovese","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Impellizzeri","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-3690","authenticated-orcid":false,"given":"Salvatore","family":"Cuzzocrea","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98165 Messina, Italy"},{"name":"Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6725-8581","authenticated-orcid":false,"given":"Rosanna","family":"Di Paola","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98165 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jns.2004.03.008","article-title":"Wallerian degeneration: History and clinical significance","volume":"220","author":"Koeppen","year":"2004","journal-title":"J. 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