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This study was undertaken to elucidate the role of endogenous H\n                      <jats:sub>2<\/jats:sub>\n                      S in the recovery of nociceptive thresholds using a mouse model of postoperative pain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male BALB\/c mice (6\u20137\u2009weeks) underwent sham or plantar incision surgery (PIS). Thermal and mechanical thresholds were assessed before surgery and 1\u20137\u2009days post\u2010PIS. At 1, 4 and 7\u2009days post\u2010PIS, the endogenous production of H\n                      <jats:sub>2<\/jats:sub>\n                      S and the expression of its synthesising enzymes\u2014cystathionine \u03b2\u2010synthase (CBS), cystathionine \u03b3\u2010lyase (CSE) and 3\u2010mercaptopyruvate sulfurtransferase (3\u2010MPST)\u2014were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One day post\u2010PIS, a reduction in H\n                      <jats:sub>2<\/jats:sub>\n                      S production was observed in the operated hindpaw, with mechanical and thermal hyperalgesia lasting 5 and 6\u2009days, respectively. CSE expression decreased in the operated hindpaw, while that of CBS increased on day 1 in the sciatic nerve and on day 4 in the L4\u2013L5 spinal cord segments. The expression of 3\u2010MPST remained unchanged. Intraplantar injection of aminooxyacetic acid (AOAA) or\n                      <jats:sc>dl<\/jats:sc>\n                      \u2010propargylglycine (PGly), inhibitors of CSE\/CBS activity, significantly delayed nociceptive threshold recovery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that while H\n                      <jats:sub>2<\/jats:sub>\n                      S signalling via CSE appears to play a limited role in postoperative pain recovery, targeting CBS activity to preserve endogenous H2S levels may offer a promising alternative for enhancing pain and accelerating recovery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>\n                      Targeting CBS to sustain H\n                      <jats:sub>2<\/jats:sub>\n                      S signalling offers a new strategy to enhance postoperative pain recovery.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70043","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T08:00:05Z","timestamp":1748505605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Elucidating the Significance of Endogenous Hydrogen Sulfide as a Novel Candidate for Postoperative Pain Recovery in a Murine Model"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2571-909X","authenticated-orcid":false,"given":"Jorge Luiz","family":"Dallazen","sequence":"first","affiliation":[{"name":"Department of Pharmacology Institute of Biomedical Sciences, University of S\u00e3o Paulo (ICB\/USP)  S\u00e3o Paulo 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