Reduced BDNF expression in the auditory cortex contributed to neonatal pain-induced hearing impairment and dendritic pruning deficiency in mice.

Autor:	Li N; Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China., Chen B; Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China.; Department of Anesthesiology, Zhongshan Hospital Fudan University, Shanghai, China., Jia G; NHC Key Laboratory of Hearing Medicine, ENT Hospital of Fudan University, Shanghai, China., Xu R; Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China., Xia Y; Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China., Lai C; NHC Key Laboratory of Hearing Medicine, ENT Hospital of Fudan University, Shanghai, China., Li G; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China., Li W; Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China yuan.han@fdeent.org wenxian.li@fdeent.org., Han Y; Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China yuan.han@fdeent.org wenxian.li@fdeent.org.
Jazyk:	angličtina
Zdroj:	Regional anesthesia and pain medicine [Reg Anesth Pain Med] 2023 Feb; Vol. 48 (2), pp. 85-92. Date of Electronic Publication: 2022 Nov 16.
DOI:	10.1136/rapm-2022-103621
Abstrakt:	Introduction: Procedural pain in neonates is associated with impaired neurodevelopment. Whether hearing development is impaired, however, remains unknown. This study examined potential cause-and-effect relationship between neonatal pain and subsequent hearing loss in mice. Methods: Male C57BL/6J mouse pups received an intra-plantar injection of complete Freund's adjuvant on postnatal day 7 or repetitive needle prick stimuli from postnatal days 0-7. Mechanical and thermal pain thresholds were tested between postnatal days 14 and 49. The auditory brainstem response test was used to determine hearing thresholds. The inner ear structures and dendritic morphology in auditory cortex were assessed using immunofluorescence and Golgi-staining. The effects of oxycodone, tropomyosin receptor kinase B agonists and antagonists were tested. Results: Neonatal pain resulted in impaired hearing in adulthood of both pain models No damage or synapse loss was found in the cochlea but increased dendritic spine density and reduced brain-derived neurotrophic factor level were found in auditory cortex in neonatal pain group. Oxycodone attenuated hearing loss and the associated changes in dendritic spine density and brain-derived neurotrophic factor changes in auditory cortex. A tropomyosin receptor kinase B agonist reversed neonatal pain-induced hearing impairment and decreased caspase 3 expression in auditory cortex. Administration of tropomyosin receptor kinase B antagonist in naïve mouse pups impaired hearing development suppressed phosphorylated-AKT, and increased caspase 3 expression. Conclusion: Chronic pain during the neonatal period resulted in impaired hearing in adulthood in mice, possibly via the brain-derived neurotrophic factor signaling pathway and dendritic spine pruning deficiency in auditory cortex. Competing Interests: Competing interests: None declared. (© American Society of Regional Anesthesia & Pain Medicine 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)
Databáze:	MEDLINE
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