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However, the role of ephrin\u2010B3\/EphBs signaling in regulation of nociceptive information is poorly understood. In the present study, formalin\u2010induced inflammatory pain, mechanical allodynia and thermal hyperalgesia, was measured using\n                    <jats:italic>Efnb3<\/jats:italic>\n                    mutant mice (\n                    <jats:italic>Efnb3<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and wild\u2010type (\n                    <jats:italic>Efnb3<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) mice. The spinal cord (L4\u20136) was selected for molecular and cellular identification by western blotting and immunofluorescence.\n                    <jats:italic>Efnb3<\/jats:italic>\n                    mutant mice showed a significant increased the thermal and mechanical threshold, followed by aberrant thin myelin sheath. Furthermore, expression of proteolipid protein (PLP) was significantly lower in L4\u20136 spinal cord of\n                    <jats:italic>Efnb3<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. These morphological and behavioral abnormalities in mutant mice were rescued by conditional knock\u2010in of wild\u2010type ephrin\u2010B3. Intrathecal administration of specific PLP siRNA significantly increased the thermal and mechanical threshold hyperalgesia in wild\u2010type mice. However, overexpressing PLP protein by AAV9\u2010PLP could decrease the sensitivity of mice to thermal and mechanical stimuli in\n                    <jats:italic>Efnb3<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, compared with scrabble\n                    <jats:italic>Efnb3<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Further,\n                    <jats:italic>Efnb3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>lacz<\/jats:italic>\n                    <\/jats:sup>\n                    mice, which have activities to initiate forward signaling, but transduce reverse signals by ephrin\u2010B3, shows normal acute pain behavior, compared with wild type mice. These findings indicate that a key molecule\n                    <jats:italic>Efnb3<\/jats:italic>\n                    act as a prominent contributor to hyperalgesia and essential roles of ephrin\u2010B3\/EphBs in nociception through a myelin\u2010mediated mechanism.\n                  <\/jats:p>","DOI":"10.1111\/fcp.12742","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T20:54:40Z","timestamp":1639428880000},"page":"262-276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Activation of spinal ephrin\u2010B3\/EphBs signaling induces hyperalgesia through a PLP\u2010mediated mechanism"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-8980","authenticated-orcid":false,"given":"Pei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmaceutical Sciences Soochow University  Suzhou Jiangsu 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