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We explored the interaction between environmental enrichment, sex and FFA1 receptor modulation in a mouse model of inflammatory pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      C57BL\/6J mice received complete Freund's adjuvant (CFA) intraplantarly and were assessed for pain and inflammation over 21\u2009days. They received the FFA1 partial agonist GW9508 (2 and 8\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) or the selective antagonist GW1100 (4\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) from days 7 to 14 under standard or environmental enrichment conditions. Paw leukocyte migration was evaluated histologically, and cortical expression of brain\u2010derived neurotrophic factor (BDNF) and FFA1 receptors was assessed by immunohistochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      GW9508 reduced mechanical sensitivity in males and females at 8 and 2\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      , respectively. Thermal sensitivity showed greater improvement at the lower dose, with synergistic effects under environmental enrichment. Only females responded to FFA1 receptor modulation in oedema assessments. GW9508 reduced paw leukocyte migration in females, particularly under EE, whereas males showed no environmental differences. GW9508 increased cortical BDNF counts in both females (2\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) and males (8\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). Cortical FFA1 receptor expression decreased in GW1100 groups, irrespective of environmental enrichment. Conversely, males showed an increased FFA1 receptor immunopositivity under GW9508 treatment (8\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) combined with environmental enrichment. BDNF and FFA1 receptor immunopositivity in the anterior cingulate cortex (ACC) was higher with GW9508 (8\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) for both sexes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>These findings highlight the interaction between environmental enrichment and FFA1 receptors, emphasizing sex differences in responses to chronic inflammatory pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70571","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T07:42:08Z","timestamp":1783582928000},"page":"5752-5768","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Free fatty acid 1 (FFA1) receptor modulation in experimental arthritis in male and female mice subjected to environmental enrichment"],"prefix":"10.1111","volume":"183","author":[{"given":"Marina","family":"Estr\u00e1zulas","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010gradua\u00e7\u00e3o em Medicina e Ci\u00eancias da Sa\u00fade, Escola de Medicina Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul  Porto Alegre Rio Grande do Sul Brazil"},{"name":"Grupo de Pesquisa em Farmacologia Aplicada: Caracteriza\u00e7\u00e3o de Mecanismos Envolvidos na Dor, Inflama\u00e7\u00e3o e C\u00e2ncer, Escola de Ci\u00eancias da Sa\u00fade e da Vida Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela W.","family":"Neculqueo","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010gradua\u00e7\u00e3o em Medicina e Ci\u00eancias da Sa\u00fade, Escola de Medicina Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul  Porto Alegre Rio Grande do Sul Brazil"},{"name":"Grupo de Pesquisa em Farmacologia Aplicada: Caracteriza\u00e7\u00e3o de Mecanismos Envolvidos na Dor, Inflama\u00e7\u00e3o e C\u00e2ncer, Escola de Ci\u00eancias da Sa\u00fade e da Vida Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana B. S.","family":"Farias","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa em Farmacologia Aplicada: Caracteriza\u00e7\u00e3o de Mecanismos Envolvidos na Dor, Inflama\u00e7\u00e3o e C\u00e2ncer, Escola de Ci\u00eancias da Sa\u00fade e da Vida Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul  Porto Alegre Rio Grande do Sul Brazil"},{"name":"Curso de Gradua\u00e7\u00e3o em Psicologia, Escola de Ci\u00eancias da Sa\u00fade e da Vida Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7738-9892","authenticated-orcid":false,"given":"Maria M.","family":"Campos","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010gradua\u00e7\u00e3o em Medicina e Ci\u00eancias da Sa\u00fade, Escola de Medicina Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul  Porto Alegre Rio Grande do Sul 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