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However, what underlies this functional and structural remodeling remains unknown. We hypothesized that spinal nociceptive afferent signaling initiates and perpetuates these pathological autonomic changes. We employed cervicothoracic epidural resiniferatoxin (RTX) to ablate spinal nociceptive neurons in male pigs before MI, and assessed autonomic and electrophysiological function four-to-six weeks post-infarction. Compared to vehicle-treated infarcted animals, epidural RTX attenuated the loss of vagal tone and baroreflex sensitivity, reduced spinal cord inflammation, glial activation, and circulating stress and inflammatory markers, and stabilized electrophysiological parameters, lowering VT\/VF inducibility. In a separate cohort, acute C7\u2013T1 nociceptive afferent ablation after chronic MI acutely restored vagal function and decreased VT\/VF inducibility. This study demonstrates that cervicothoracic spinal nociceptive afferents significantly contribute to MI-induced autonomic remodeling and VT\/VF, providing novel insight into the mechanisms underlying sympathovagal imbalance after MI.<\/jats:p>","DOI":"10.1038\/s41467-026-75759-2","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:32:21Z","timestamp":1784755941000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spinal nociceptive denervation impedes subsequent chronic autonomic remodeling after myocardial infarction in male swine"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0672-9463","authenticated-orcid":false,"given":"Valerie Y. 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