{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:42:14Z","timestamp":1762004534361},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,7,17]],"date-time":"2013-07-17T00:00:00Z","timestamp":1374019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Smad\u2010interacting protein 1 (also named <jats:italic><jats:styled-content style=\"fixed-case\">Z<\/jats:styled-content>eb2<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">Z<\/jats:styled-content>fhx1b<\/jats:italic>) is a transcription factor that plays an important role in neuronal development and, when mutated, causes <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>owat\u2013<jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>ilson syndrome (<jats:styled-content style=\"fixed-case\">MWS<\/jats:styled-content>). A corresponding mouse model carrying a heterozygous <jats:italic><jats:styled-content style=\"fixed-case\">Z<\/jats:styled-content>eb2<\/jats:italic> deletion was comprehensively analysed in the <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>erman <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>ouse Clinic. The most prominent phenotype was the reduced pain sensitivity. In this study, we investigated the role of <jats:italic><jats:styled-content style=\"fixed-case\">Z<\/jats:styled-content>eb2<\/jats:italic> in inflammatory and neuropathic pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For this, we tested mutant <jats:italic><jats:styled-content style=\"fixed-case\">Z<\/jats:styled-content>eb2<\/jats:italic> animals in different models of inflammatory pain like abdominal constriction, formalin and carrageenan test. Furthermore, we studied the pain reactivity of the mice after peripheral nerve ligation. To examine the nociceptive transmission of primary sensory dorsal root ganglia (<jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content>) neurons, we determined the neuronal activity in the spinal dorsal horn after the formalin test using staining of c\u2010<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>os. Next, we characterized the neuronal cell population in the <jats:styled-content style=\"fixed-case\">DRGs<\/jats:styled-content> and in the sciatic nerve to study the effect of the <jats:italic><jats:styled-content style=\"fixed-case\">Z<\/jats:styled-content>eb2<\/jats:italic> mutation on peripheral nerve morphology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The present data show that <jats:italic><jats:styled-content style=\"fixed-case\">Z<\/jats:styled-content>eb2<\/jats:italic> is involved in the development of primary sensory <jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content> neurons, especially of <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010 and <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b4 fibres. These alterations contribute to a hypoalgesic phenotype in inflammatory but not in neuropathic pain in these <jats:italic><jats:styled-content style=\"fixed-case\">Z<\/jats:styled-content>eb2<\/jats:italic><jats:sup><jats:italic>+\/<\/jats:italic>\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that the under\u2010reaction to pain observed in <jats:styled-content style=\"fixed-case\">MWS<\/jats:styled-content> patients results from a reduced responsivity to nociceptive stimulation rather than an inability to communicate discomfort.<\/jats:p><\/jats:sec>","DOI":"10.1002\/j.1532-2149.2013.00366.x","type":"journal-article","created":{"date-parts":[[2013,7,17]],"date-time":"2013-07-17T09:13:57Z","timestamp":1374052437000},"page":"249-257","source":"Crossref","is-referenced-by-count":12,"title":["Smad\u2010interacting protein 1 affects acute and tonic, but not chronic 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