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In this study, we used an in vitro model of paclitaxel-induced neuropathic pain to investigate the role of glial activation in TRPV1 receptor function.\nUsing whole-cell patch-clamp recordings from superficial dorsal horn neurons in acute spinal cord slices, we evaluated the effects of minocycline (MX), a glial cell inhibitor, and ISO-1, a macrophage migration inhibitory factor (MIF) antagonist, on paclitaxel-induced synaptic changes. Our results demonstrate that acute paclitaxel application enhances nociceptive signaling and impairs capsaicin-induced TRPV1 receptor tachyphylaxis, leading to sustained hyperactivity. Minocycline preincubation effectively mitigated paclitaxel-induced sensitization, restoring normal nociceptive signaling, whereas acute minocycline treatment failed to prevent these changes. ISO-1 in vitro co-incubation with paclitaxel did not affect the paclitaxel-induced changes. These findings offer novel insight into the intricate interactions among neuroinflammatory mediators, glial cell activation, and TRPV1 receptor sensitization in paclitaxel-induced neuropathic pain. The differential effects of acute versus prolonged pre-incubation minocycline application suggest the importance of sustained glial inhibition for effective outcomes and neuropathic pain management.<\/jats:p>","DOI":"10.33549\/physiolres.935599","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T12:07:09Z","timestamp":1756728429000},"page":"677-691","source":"Crossref","is-referenced-by-count":3,"title":["Glial Activation Enhances Spinal TRPV1 Receptor Sensitivity in a Paclitaxel Model of Neuropathic Pain"],"prefix":"10.33549","author":[{"given":"J","family":"Slepicka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Palecek","sequence":"additional","affiliation":[{"name":"Laboratory of Pain Research, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic. 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