Skip to main content

Advertisement

SpringerLink
Log in

Heat Shock Protein 22 Attenuates Nerve Injury-induced Neuropathic Pain Via Improving Mitochondrial Biogenesis and Reducing Oxidative Stress Mediated By Spinal AMPK/PGC-1α Pathway in Male Rats

  • Research
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

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 γ coactivator 1α (PGC-1α) pathway in male rats with SNI. Furthermore, it was also demonstrated that AMPK antagonist (compound C, CC) or PGC-1α 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-1α pathway in male rats with SNI.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available from the corresponding author (Mei Wei) upon request.

Code Availability

Not applicable.

References

  • Bouchez C, Devin A (2019) Mitochondrial Biogenesis and mitochondrial reactive oxygen species (ROS): a complex relationship regulated by the cAMP/PKA signaling pathway. Cells 8:287

  • Cao Q, Chen J, Zhang Z, Shu S, Qian Y, Yang L, Xu L, Zhang Y, Bao X, Xia S, Yang H, Xu Y, Qiu S (2023) Astrocytic CXCL5 hinders microglial phagocytosis of myelin debris and aggravates white matter injury in chronic cerebral ischemia. J Neuroinflammation 20:105

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cao S, Wang C, Yan J, Li X, Wen J, Hu C (2020) Curcumin ameliorates oxidative stress-induced intestinal barrier injury and mitochondrial damage by promoting Parkin dependent mitophagy through AMPK-TFEB signal pathway. Free Radic Biol Med 147:8–22

    Article  PubMed  CAS  Google Scholar 

  • Chen QM (2022) Nrf2 for protection against oxidant generation and mitochondrial damage in cardiac injury. Free Radic Biol Med 179:133–143

    Article  PubMed  CAS  Google Scholar 

  • Chen N, Ge MM, Li DY, Wang XM, Liu DQ, Ye DW, Tian YK, Zhou YQ, Chen JP (2021a) beta2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis. Biomed Pharmacother 144:112331

    Article  PubMed  CAS  Google Scholar 

  • Chen Q, Kong L, Xu Z, Cao N, Tang X, Gao R, Zhang J, Deng S, Tan C, Zhang M, Wang Y, Zhang L, Ma K, Li L, Si J (2021b) The role of TMEM16A/ERK/NK-1 signaling in dorsal root ganglia neurons in the development of neuropathic pain induced by spared nerve injury (SNI). Mol Neurobiol 58:5772–5789

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen XJ, Wang L, Song XY (2020) Mitoquinone alleviates vincristine-induced neuropathic pain through inhibiting oxidative stress and apoptosis via the improvement of mitochondrial dysfunction. Biomed Pharmacother 125:110003

    Article  PubMed  CAS  Google Scholar 

  • De Gregorio D, McLaughlin RJ, Posa L, Ochoa-Sanchez R, Enns J, Lopez-Canul M, Aboud M, Maione S, Comai S, Gobbi G (2019) Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain 160:136–150

    Article  PubMed  Google Scholar 

  • Depre C, Wang L, Sui X, Qiu H, Hong C, Hedhli N, Ginion A, Shah A, Pelat M, Bertrand L, Wagner T, Gaussin V, Vatner SF (2006) H11 kinase prevents myocardial infarction by preemptive preconditioning of the heart. Circ Res 98:280–288

    Article  PubMed  CAS  Google Scholar 

  • Drake JC et al (2021) Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy. Proc Natl Acad Sci U S A 118:e2025932118

  • Fan H, Ding R, Liu W, Zhang X, Li R, Wei B, Su S, Jin F, Wei C, He X, Li X, Duan C (2021) Heat shock protein 22 modulates NRF1/TFAM-dependent mitochondrial biogenesis and DRP1-sparked mitochondrial apoptosis through AMPK-PGC1alpha signaling pathway to alleviate the early brain injury of subarachnoid hemorrhage in rats. Redox Biol 40:101856

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Flatters SJL, Bennett GJ (2006) Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: evidence for mitochondrial dysfunction. Pain 122:245–257

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gao X, Kim HK, Mo Chung J, Chung K (2007) Reactive oxygen species (ROS) are involved in enhancement of NMDA-receptor phosphorylation in animal models of pain. Pain 131:262–271

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Garcia D, Hellberg K, Chaix A, Wallace M, Herzig S, Badur MG, Lin T, Shokhirev MN, Pinto AFM, Ross DS, Saghatelian A, Panda S, Dow LE, Metallo CM, Shaw RJ (2019) Genetic liver-specific AMPK activation protects against Diet-Induced obesity and NAFLD. Cell Rep 26:192-208e196

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo A, Li K, Tian HC, Fan Z, Chen QN, Yang YF, Yu J, Wu YX, Xiao Q (2021) FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK/SIRT-1/PGC-alpha pathway. J Cell Mol Med 25:3585–3600

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Han YC, Tang SQ, Liu YT, Li AM, Zhan M, Yang M, Song N, Zhang W, Wu XQ, Peng CH, Zhang H, Yang S (2021) AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice. Cell Death Dis 12:925

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hao L, Zhong W, Dong H, Guo W, Sun X, Zhang W, Yue R, Li T, Griffiths A, Ahmadi AR, Sun Z, Song Z, Zhou Z (2021) ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1-TFAM signalling in alcoholic steatohepatitis. Gut 70:1933–1945

    Article  PubMed  CAS  Google Scholar 

  • Herzig S, Shaw RJ (2018) AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol 19:121–135

    Article  PubMed  CAS  Google Scholar 

  • Jiang J, Xu L, Yang L, Liu S, Wang Z (2023) Mitochondrial-derived peptide MOTS-c ameliorates spared nerve Injury-Induced Neuropathic Pain in mice by inhibiting Microglia activation and neuronal oxidative damage in the spinal cord via the AMPK pathway. ACS Chem Neurosci 14:2362–2374

    Article  PubMed  CAS  Google Scholar 

  • Jo HS, Kim DW, Shin MJ, Cho SB, Park JH, Lee CH, Yeo EJ, Choi YJ, Yeo HJ, Sohn EJ, Son O, Cho SW, Kim DS, Yu YH, Lee KW, Park J, Eum WS, Choi SY (2017) Tat-HSP22 inhibits oxidative stress-induced hippocampal neuronal cell death by regulation of the mitochondrial pathway. Mol Brain 10:1

    Article  PubMed  PubMed Central  Google Scholar 

  • Kang D, Kim SH, Hamasaki N (2007) Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. Mitochondrion 7:39–44

    Article  PubMed  CAS  Google Scholar 

  • Khasabova IA, Khasabov SG, Olson JK, Uhelski ML, Kim AH, Albino-Ramirez AM, Wagner CL, Seybold VS, Simone DA (2019) Pioglitazone, a PPARgamma agonist, reduces cisplatin-evoked neuropathic pain by protecting against oxidative stress. Pain 160:688–701

    Article  PubMed  CAS  Google Scholar 

  • Kumar Kalvala A, Bagde A, Arthur P, Kumar Surapaneni S, Ramesh N, Nathani A, Singh M (2022) Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents. Int Immunopharmacol 107:108693

    Article  PubMed  CAS  Google Scholar 

  • Lee DZ, Chung JM, Chung K, Kang MG (2012) Reactive oxygen species (ROS) modulate AMPA receptor phosphorylation and cell-surface localization in concert with pain-related behavior. Pain 153:1905–1915

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li Y, Feng YF, Liu XT, Li YC, Zhu HM, Sun MR, Li P, Liu B, Yang H (2021a) Songorine promotes cardiac mitochondrial biogenesis via Nrf2 induction during sepsis. Redox Biol 38:101771

    Article  PubMed  CAS  Google Scholar 

  • Li J, Tian M, Hua T, Wang H, Yang M, Li W, Zhang X, Yuan H (2021b) Combination of autophagy and NFE2L2/NRF2 activation as a treatment approach for neuropathic pain. Autophagy 17:4062–4082

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li F, Yang B, Li T, Gong X, Zhou F, Hu Z (2019) HSPB8 over-expression prevents disruption of blood-brain barrier by promoting autophagic flux after cerebral ischemia/reperfusion injury. J Neurochem 148:97–113

    Article  PubMed  CAS  Google Scholar 

  • Li J, Zhang L, Xu C, Shen YY, Lin YH, Zhang Y, Wu HY, Chang L, Zhang YD, Chen R, Zhang ZP, Luo CX, Li F, Zhu DY (2021c) A pain killer without analgesic tolerance designed by co-targeting PSD-95-nNOS interaction and alpha2-containning GABA(A)rs. Theranostics 11:5970–5985

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lin SC, Hardie DG (2018) AMPK: sensing glucose as well as cellular energy status. Cell Metab 27:299–313

    Article  PubMed  CAS  Google Scholar 

  • Liu ZY, Song ZW, Guo SW, He JS, Wang SY, Zhu JG, Yang HL, Liu JB (2019) CXCL12/CXCR4 signaling contributes to neuropathic pain via central sensitization mechanisms in a rat spinal nerve ligation model. CNS Neurosci Ther 25:922–936

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lu X, Xuan W, Li J, Yao H, Huang C, Li J (2021) AMPK protects against alcohol-induced liver injury through UQCRC2 to up-regulate mitophagy. Autophagy 17:3622–3643

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maixner DW, Yan X, Hooks SB, Weng HR (2016) AMPKalpha1 knockout enhances nociceptive behaviors and spinal glutamatergic synaptic activities via production of reactive oxygen species in the spinal dorsal horn. Neuroscience 326:158–169

    Article  PubMed  CAS  Google Scholar 

  • Malik N, Ferreira BI, Hollstein PE, Curtis SD, Trefts E, Weiser Novak S, Yu J, Gilson R, Hellberg K, Fang L, Sheridan A, Hah N, Shadel GS, Manor U, Shaw RJ (2023) Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1. Science 380:eabj5559

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mattson MP, Gleichmann M, Cheng A (2008) Mitochondria in neuroplasticity and neurological disorders. Neuron 60:748–766

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Park SE, Neupane C, Noh C, Sharma R, Shin HJ, Pham TL, Lee GS, Park KD, Lee CJ, Kang DW, Lee SY, Kim HW, Park JB (2022) Antiallodynic effects of KDS2010, a novel MAO-B inhibitor, via ROS-GABA inhibitory transmission in a paclitaxel-induced tactile hypersensitivity model. Mol Brain 15:41

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Qiu H, Lizano P, Laure L, Sui X, Rashed E, Park JY, Hong C, Gao S, Holle E, Morin D, Dhar SK, Wagner T, Berdeaux A, Tian B, Vatner SF, Depre C (2011) H11 kinase/heat shock protein 22 deletion impairs both nuclear and mitochondrial functions of STAT3 and accelerates the transition into heart failure on cardiac overload. Circulation 124:406–415

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ren Y, Shen HM (2019) Critical role of AMPK in redox regulation under glucose starvation. Redox Biol 25:101154

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shao S, Xu CB, Chen CJ, Shi GN, Guo QL, Zhou Y, Wei YZ, Wu L, Shi JG, Zhang TT (2021) Divanillyl sulfone suppresses NLRP3 inflammasome activation via inducing mitophagy to ameliorate chronic neuropathic pain in mice. J Neuroinflammation 18:142

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Simmons EC, Scholpa NE, Schnellmann RG (2020) Mitochondrial biogenesis as a therapeutic target for traumatic and neurodegenerative CNS diseases. Exp Neurol 329:113309

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sun J, Song FH, Wu JY, Zhang LQ, Li DY, Gao SJ, Liu DQ, Zhou YQ, Mei W (2022) Sestrin2 overexpression attenuates osteoarthritis pain via induction of AMPK/PGC-1alpha-mediated mitochondrial biogenesis and suppression of neuroinflammation. Brain Behav Immun 102:53–70

    Article  PubMed  CAS  Google Scholar 

  • Wang J-W, Ye X-Y, Wei N, Wu S-S, Zhang Z-H, Luo G-H, Li X, Li J, Cao H (2022) Reactive oxygen species contributes to type 2 Diabetic Neuropathic Pain via the thioredoxin-interacting Protein-NOD–Like receptor protein 3-N-Methyl-D-Aspartic acid receptor 2B pathway. Anesth Analgesia 135:865–876

    Article  CAS  Google Scholar 

  • Wen W, Chen X, Huang Z, Chen D, Chen H, Luo Y, He J, Zheng P, Yu J, Yu B (2020) Resveratrol regulates muscle fiber type conversion via mir-22-3p and AMPK/SIRT1/PGC-1alpha pathway. J Nutr Biochem 77:108297

    Article  PubMed  CAS  Google Scholar 

  • Wu W, Lai L, Xie M, Qiu H (2020) Insights of heat shock protein 22 in the cardiac protection against ischemic oxidative stress. Redox Biol 34:101555

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu M, Zhang C, Xie M, Zhen Y, Lai B, Liu J, Qiao L, Liu S, Shi D (2021) Compartmentally scavenging hepatic oxidants through AMPK/SIRT3-PGC1alpha axis improves mitochondrial biogenesis and glucose catabolism. Free Radic Biol Med 168:117–128

    Article  PubMed  CAS  Google Scholar 

  • Xiang H-C, Lin L-X, Hu X-F, Zhu H, Li H-P, Zhang R-Y, Hu L, Liu W-T, Zhao Y-L, Shu Y, Pan H-L, Li M (2019) AMPK activation attenuates inflammatory pain through inhibiting NF-κB activation and IL-1β expression. J Neuroinflamm 16:34

  • Xu J, Ji L, Ruan Y, Wan Z, Lin Z, Xia S, Tao L, Zheng J, Cai L, Wang Y, Liang X, Cai X (2021) UBQLN1 mediates sorafenib resistance through regulating mitochondrial biogenesis and ROS homeostasis by targeting PGC1beta in hepatocellular carcinoma. Signal Transduct Target Ther 6:190

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xu Y, Nowrangi D, Liang H, Wang T, Yu L, Lu T, Lu Z, Zhang JH, Luo B, Tang J (2020a) DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage. J Neuroinflammation 17:130

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xu J, Wei X, Gao F, Zhong X, Guo R, Ji Y, Zhou X, Chen J, Yao P, Liu X, Wei X (2020b) Nicotinamide adenine dinucleotide phosphate oxidase 2-derived reactive oxygen species contribute to long-term potentiation of C-fiber-evoked field potentials in spinal dorsal horn and persistent mirror-image pain following high-frequency stimulus of the sciatic nerve. Pain 161:758–772

    Article  PubMed  CAS  Google Scholar 

  • Yingze Y, Zhihong J, Tong J, Yina L, Zhi Z, Xu Z, Xiaoxing X, Lijuan G (2022) NOX2-mediated reactive oxygen species are double-edged swords in focal cerebral ischemia in mice. J Neuroinflammation 19:184

    Article  PubMed  PubMed Central  Google Scholar 

  • Yowtak J, Lee KY, Kim HY, Wang J, Kim HK, Chung K, Chung JM (2011) Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA release. Pain 152:844–852

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yu L, Liang Q, Zhang W, Liao M, Wen M, Zhan B, Bao H, Cheng X (2019) HSP22 suppresses diabetes-induced endothelial injury by inhibiting mitochondrial reactive oxygen species formation. Redox Biol 21:101095

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang LQ, Gao SJ, Sun J, Li DY, Wu JY, Song FH, Liu DQ, Zhou YQ, Mei W (2022a) DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation. J Neuroinflammation 19:129

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang L, Tan X, Song F, Li D, Wu J, Gao S, Sun J, Liu D, Zhou Y, Mei W (2024) Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model. Neural Regen Res 19:687–696

    Article  PubMed  Google Scholar 

  • Zhang LQ, Zhou YQ, Li JY, Sun J, Zhang S, Wu JY, Gao SJ, Tian XB, Mei W (2022b) 5-HT(1F) receptor agonist ameliorates mechanical Allodynia in Neuropathic Pain via induction of mitochondrial Biogenesis and suppression of Neuroinflammation. Front Pharmacol 13:834570

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhao X, Li XL, Liu X, Wang C, Zhou DS, Ma Q, Zhou WH, Hu ZY (2015) Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors. Pharmacol Res 102:286–297

    Article  PubMed  CAS  Google Scholar 

  • Zhao M, Wang Y, Li L, Liu S, Wang C, Yuan Y, Yang G, Chen Y, Cheng J, Lu Y, Liu J (2021) Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance. Theranostics 11:1845–1863

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhou YQ, Liu DQ, Chen SP, Sun J, Zhou XR, Rittner H, Mei W, Tian YK, Zhang HX, Chen F, Ye DW (2018) Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain. Redox Biol 14:391–397

    Article  PubMed  CAS  Google Scholar 

  • Zhou D, Zhou M, Wang Z, Fu Y, Jia M, Wang X, Liu M, Zhang Y, Sun Y, Lu Y, Tang W, Yi F (2019) PGRN acts as a novel regulator of mitochondrial homeostasis by facilitating mitophagy and mitochondrial biogenesis to prevent podocyte injury in diabetic nephropathy. Cell Death Dis 10:524

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by grants from the National Natural Science Foundation of China, Nos. 82271291 and 82071556 (both to Wei Mei); 82001198 (Yaqun Zhou); 82101310 (Daiqiang Liu).

Author information

Authors and Affiliations

  1. 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

    Longqing Zhang, Lin Liu, Danyang Li, Jiayi Wu, Shaojie Gao, Fanhe Song, Yaqun Zhou, Daiqiang Liu & Wei Mei

Authors
  1. Longqing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danyang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiayi Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shaojie Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fanhe Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yaqun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daiqiang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wei Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Wei Mei developed the concept of the study; Longqing Zhang designed the study; Lin Liu, Danyang Li and Jiayi Wu provided experimental support; Shaojie Gao, Fanhe Song, Yaqun Zhou, and Daiqiang Liu analyzed and interpreted the data. LQZ wrote the paper. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Daiqiang Liu or Wei Mei.

Ethics declarations

Ethics Approval and Consent to Participate

All experiments were conducted in accordance with the Animal Research Reporting of in Vivo Experiments (ARRIVE) Guidelines. This study was approved by the Experimental Animal Care and Use Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Consent for Publication

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, L., Liu, L., Li, D. et al. Heat Shock Protein 22 Attenuates Nerve Injury-induced Neuropathic Pain Via Improving Mitochondrial Biogenesis and Reducing Oxidative Stress Mediated By Spinal AMPK/PGC-1α Pathway in Male Rats. J Neuroimmune Pharmacol 19, 5 (2024). https://doi.org/10.1007/s11481-024-10100-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11481-024-10100-6

Keywords

Search

Navigation