PAIN Reports, Год журнала: 2025, Номер 10(4), С. e1288 - e1288

Опубликована: Май 27, 2025

Commentary on: Perez-Miller S, Khanna R. Beyond single targets: leveraging degeneracy in sodium channels for osteoarthritis analgesia. PAIN Rep 2025. DOI: 10.1097/PR9.0000000000001289. Objective: Multiple voltage-gated (Na V s) the peripheral sensory neurons (PSNs) regulate action potentials and their dysfunction contributes to pain pathogenesis of (OA). A combined block multiple Na subtypes selectively PSNs may, therefore, represent an effective analgesic approach OA painful neuropathy. Methods: To test this hypothesis, we generated recombinant adeno-associated virus (AAV) encoding a potent inhibitory peptide aptamer, termed iPA1, that has multipronged feature inhibiting tetrodotoxin-sensitive 1.7, 1.6, 1.1, 1.3, characterized our recent report. Adeno-associated virus-encoded iPA1 was delivered into ipsilateral lumbar 4/5 dorsal root ganglia rats 2 weeks after induction knee monoiodoacetate-OA (MIA-OA) evoked spontaneous behaviors were followed 6 weeks. Results: Expression selective produced significant comparable mitigations behavior reversal weight-bearing asymmetry both male female MIA-OA rats. Whole-cell current-clamp recordings showed AAV-mediated expression normalized potential firing from MIA animals, suggesting attenuated by, at least part, reversing neuronal hyperexcitability. Conclusion: Together, these results support (1) s pathways contribute (2) is promising lead that, with AAV-targeted delivery pathological ganglia, may be viable peripherally PSN-targeting strategy mitigating chronic behaviors.

Язык: Английский