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Rats were submitted to zymosan\u2010induced arthritis of the temporomandibular joint or infraorbital nerve constriction, and treated intrathecally with a P\n                    <jats:sub>2<\/jats:sub>\n                    X\n                    <jats:sub>7<\/jats:sub>\n                    antagonist, a cathepsin S inhibitor or a p\u201038 mitogen\u2010activated protein kinase (MAPK) inhibitor. Mechanical hyperalgesia was evaluated 4 and 6\u2009h following arthritis induction or 7 and 14\u2009days following nerve ligation. The expression of the receptor CX\n                    <jats:sub>3<\/jats:sub>\n                    CR\n                    <jats:sub>1<\/jats:sub>\n                    , phospho\u2010p\u201038 MAPK, ionized calcium\u2010binding adapter molecule\u20101 (Iba\u20101), and glutamine synthetase and the morphological changes in microglia and SGCs were evaluated by confocal microscopy. In both inflammatory and neuropathic models, untreated animals presented a higher expression of CX\n                    <jats:sub>3<\/jats:sub>\n                    CR\n                    <jats:sub>1<\/jats:sub>\n                    and developed hyperalgesia and up\u2010regulation of phospho\u2010p\u201038 MAPK, which was prevented by all drugs (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.05). The number of microglial processes endpoints and the total branch length were lower in the untreated animals, but the overall immunolabeling of Iba\u20101 was altered only in neuropathic rats (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.05). The mean area of SGCs per neuron was significantly altered only in the inflammatory model (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.05). All morphological alterations were reverted by modulating the fractalkine pathway (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.05). In conclusion, the blockage of the fractalkine pathway seemed to be a possible therapeutic strategy for inflammatory and neuropathic orofacial pain, reducing mechanical hyperalgesia by impairing the phosphorylation of p\u201038 MAPK and reverting morphological alterations in microglia and SGCs.\n                  <\/jats:p>","DOI":"10.1002\/jnr.25269","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T01:31:20Z","timestamp":1701135080000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Blockage of the fractalkine pathway reduces hyperalgesia and prevents morphological glial alterations\u2014Comparison between inflammatory and neuropathic orofacial pain in male rats"],"prefix":"10.1002","volume":"102","author":[{"given":"Mario Roberto Pontes","family":"Lisboa","sequence":"first","affiliation":[{"name":"Department of Morphology, Faculty of Medicine Federal University of Cear\u00e1 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