PMID- 38319409 OWN - NLM STAT- MEDLINE DCOM- 20240207 LR - 20240207 IS - 1557-1904 (Electronic) IS - 1557-1890 (Linking) VI - 19 IP - 1 DP - 2024 Feb 6 TI - Heat Shock Protein 22 Attenuates Nerve Injury-induced Neuropathic Pain Via Improving Mitochondrial Biogenesis and Reducing Oxidative Stress Mediated By Spinal AMPK/PGC-1alpha Pathway in Male Rats. PG - 5 LID - 10.1007/s11481-024-10100-6 [doi] AB - Heat shock protein 22 (hsp22) plays a significant role in mitochondrial biogenesis and redox balance. Moreover, it's well accepted that the impairment of mitochondrial biogenesis and redox imbalance contributes to the progress of neuropathic pain. However, there is no available evidence indicating that hsp22 can ameliorate mechanical allodynia and thermal hyperalgesia, sustain mitochondrial biogenesis and redox balance in rats with neuropathic pain. In this study, pain behavioral test, western blotting, immunofluorescence staining, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Dihydroethidium staining are applied to confirm the role of hsp22 in a male rat model of spared nerve injury (SNI). Our results indicate that hsp22 was significantly decreased in spinal neurons post SNI. Moreover, it was found that intrathecal injection (i.t.) with recombinant heat shock protein 22 protein (rhsp22) ameliorated mechanical allodynia and thermal hyperalgesia, facilitated nuclear respiratory factor 1 (NRF1)/ mitochondrial transcription factor A (TFAM)-dependent mitochondrial biogenesis, decreased the level of reactive oxygen species (ROS), and suppressed oxidative stress via activation of spinal adenosine 5'monophosphate-activated protein kinase (AMPK)/ peroxisome proliferative activated receptor gamma coactivator 1alpha (PGC-1alpha) pathway in male rats with SNI. Furthermore, it was also demonstrated that AMPK antagonist (compound C, CC) or PGC-1alpha siRNA reversed the improved mechanical allodynia and thermal hyperalgesia, mitochondrial biogenesis, oxidative stress, and the decreased ROS induced by rhsp22 in male rats with SNI. These results revealed that hsp22 alleviated mechanical allodynia and thermal hyperalgesia, improved the impairment of NRF1/TFAM-dependent mitochondrial biogenesis, down-regulated the level of ROS, and mitigated oxidative stress through stimulating the spinal AMPK/PGC-1alpha pathway in male rats with SNI. CI - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Zhang, Longqing AU - Zhang L AD - Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Liu, Lin AU - Liu L AD - Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Li, Danyang AU - Li D AD - Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Wu, Jiayi AU - Wu J AD - Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Gao, Shaojie AU - Gao S AD - Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Song, Fanhe AU - Song F AD - Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Zhou, Yaqun AU - Zhou Y AD - Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. FAU - Liu, Daiqiang AU - Liu D AD - Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. dqliu2017@hotmail.com. FAU - Mei, Wei AU - Mei W AD - Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. wmei@hust.edu.cn. LA - eng GR - 82001198/National Natural Science Foundation of China/ GR - 82101310/National Natural Science Foundation of China/ GR - 82271291 and 82071556/National Natural Science Foundation of China/ PT - Journal Article DEP - 20240206 PL - United States TA - J Neuroimmune Pharmacol JT - Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology JID - 101256586 RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - 0 (Heat-Shock Proteins) RN - 0 (Reactive Oxygen Species) RN - 0 (HspB8 protein, rat) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) SB - IM MH - Animals MH - Male MH - Rats MH - AMP-Activated Protein Kinases/metabolism MH - *Heat-Shock Proteins/metabolism MH - *Hyperalgesia/drug therapy MH - *Neuralgia MH - Organelle Biogenesis MH - Oxidation-Reduction MH - Oxidative Stress MH - Reactive Oxygen Species/metabolism MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism OTO - NOTNLM OT - Mitochondrial biogenesis OT - Mitochondrial dysfunction OT - Neuropathic pain OT - Oxidative stress OT - ROS OT - hsp22 EDAT- 2024/02/06 13:43 MHDA- 2024/02/07 06:42 CRDT- 2024/02/06 11:07 PHST- 2023/07/25 00:00 [received] PHST- 2023/11/14 00:00 [accepted] PHST- 2024/02/07 06:42 [medline] PHST- 2024/02/06 13:43 [pubmed] PHST- 2024/02/06 11:07 [entrez] AID - 10.1007/s11481-024-10100-6 [pii] AID - 10.1007/s11481-024-10100-6 [doi] PST - epublish SO - J Neuroimmune Pharmacol. 2024 Feb 6;19(1):5. doi: 10.1007/s11481-024-10100-6.