Research progress on the role of programmed cell death in the mechanism of neuropathic pain_West China Medical Journal

Authors：

LIU Xiang ¹ , GAO Wei ¹ , FAN Xiaohua ¹ , WANG Shuanglian ² ,  WANG Chao ¹

1. Department of Rehabilitation, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P. R. China;
2. Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, Shandong 250117, P. R. China;

Corresponding author：

WANG Chao, Email: wangchao@sdfmu.edu.cn

Keywords：

Neuropathic pain; programmed cell death; apoptosis; autophagy; ferroptosis

DOI：

10.7507/1002-0179.202408164

Video：

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Abstract Full text Figures/Tables Video References Cited by

Neuropathic pain (NP) is a pathological state caused by damage or disease to the somatosensory nervous system. Programmed cell death (PCD) is an orderly process of cell death regulated by both intrinsic signals and external stimuli. In recent years, an increasing number of studies have shown that PCD plays a key regulatory role in the pathogenesis of NP. This article reviews the molecular mechanisms of various types of PCD and their specific roles in NP, in order to provide new research directions for the prevention, diagnosis, and treatment of NP.

Citation： LIU Xiang, GAO Wei, FAN Xiaohua, WANG Shuanglian, WANG Chao. Research progress on the role of programmed cell death in the mechanism of neuropathic pain. West China Medical Journal, 2025, 40(1): 125-131. doi: 10.7507/1002-0179.202408164 Copy

1.	Scholz J, Finnerup NB, Attal N, et al. The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain, 2019, 160(1): 53-59.
2.	Chen O, Donnelly CR, Ji RR. Regulation of pain by neuro-immune interactions between macrophages and nociceptor sensory neurons. Curr Opin Neurobiol, 2020, 62: 17-25.
3.	Gilron I, Baron R, Jensen T. Neuropathic pain: principles of diagnosis and treatment. Mayo Clin Proc, 2015, 90(4): 532-545.
4.	Tang D, Kang R, Berghe TV, et al. The molecular machinery of regulated cell death. Cell Res, 2019, 29(5): 347-364.
5.	Kowalski S, Karska J, Łapińska Z, et al. An overview of programmed cell death: apoptosis and pyroptosis-mechanisms, differences, and significance in organism physiology and pathophysiology. J Cell Biochem, 2023, 124(6): 765-784.
6.	Vogeler S, Carboni S, Li X, et al. Phylogenetic analysis of the caspase family in bivalves: implications for programmed cell death, immune response and development. BMC Genomics, 2021, 22(1): 80.
7.	Yang JK. Death effecter domain for the assembly of death-inducing signaling complex. Apoptosis, 2015, 20(2): 235-239.
8.	Elena-Real CA, Díaz-Quintana A, González-Arzola K, et al. Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent apaf-1 inhibition. Cell Death Dis, 2018, 9(3): 365.
9.	Erekat NS. Programmed cell death in cerebellar Purkinje neurons. J Integr Neurosci, 2022, 21(1): 30.
10.	Dhuriya YK, Sharma D. Necroptosis: a regulated inflammatory mode of cell death. J Neuroinflammation, 2018, 15(1): 199.
11.	Gradl G, Gaida S, Gierer P, et al. In vivo evidence for apoptosis, but not inflammation in the hindlimb muscle of neuropathic rats. Pain, 2004, 112(1/2): 121-130.
12.	Sekiguchi M, Sekiguchi Y, Konno S, et al. Comparison of neuropathic pain and neuronal apoptosis following nerve root or spinal nerve compression. Eur Spine J, 2009, 18(12): 1978-1985.
13.	Kaeidi A, Esmaeili-Mahani S, Sheibani V, et al. Olive (Olea europaea L. ) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies. J Ethnopharmacol, 2011, 136(1): 188-196.
14.	Long Y, Liang F, Gao C, et al. Hyperbaric oxygen therapy reduces apoptosis after spinal cord injury in rats. Int J Clin Exp Med, 2014, 7(11): 4073-4081.
15.	Dhani S, Zhao Y, Zhivotovsky B. A long way to go: caspase inhibitors in clinical use. Cell Death Dis, 2021, 12(10): 949.
16.	Hyman BT, Yuan J. Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology. Nat Rev Neurosci, 2012, 13(6): 395-406.
17.	Deng Y, Yang L, Xie Q, et al. Protein kinase A is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis. Mediators Inflamm, 2020, 2020: 6420425.
18.	Liao MF, Yeh SR, Lu KT, et al. Interactions between autophagy, proinflammatory cytokines, and apoptosis in neuropathic pain: granulocyte colony stimulating factor as a multipotent therapy in rats with chronic constriction injury. Biomedicines, 2021, 9(5): 542.
19.	Yu Z, Jiang N, Su W, et al. Necroptosis: a novel pathway in neuroinflammation. Front Pharmacol, 2021, 12: 701564.
20.	Ohsumi Y. Historical landmarks of autophagy research. Cell Res, 2014, 24(1): 9-23.
21.	Liang YX, Wang NN, Zhang ZY, et al. Necrostatin-1 ameliorates peripheral nerve injury-induced neuropathic pain by inhibiting the RIP1/RIP3 pathway. Front Cell Neurosci, 2019, 13: 211.
22.	Duan Y, Li Q, Zhou Y, et al. Activation of the TNF-α-necroptosis pathway in parvalbumin-expressing interneurons of the anterior cingulate cortex contributes to neuropathic pain. Int J Mol Sci, 2023, 24(20): 15454.
23.	Dong Yang M, Ming Jie W, Hui Zhou L, et al. Spinal microglial M1 polarization contributes paclitaxel-induced neuropathic pain by triggering cells necroptosis. J Biochem Mol Toxicol, 2024, 38(3): e23669.
24.	Binshtok AM, Wang H, Zimmermann K, et al. Nociceptors are interleukin-1beta sensors. J Neurosci, 2008, 28(52): 14062-14073.
25.	Yang Y, Klionsky DJ. Autophagy and disease: unanswered questions. Cell Death Differ, 2020, 27(3): 858-871.
26.	Lahiri V, Hawkins WD, Klionsky DJ. Watch what you (self-) eat: autophagic mechanisms that modulate metabolism. Cell Metab, 2019, 29(4): 803-826.
27.	Yamahara K, Yasuda M, Kume S, et al. The role of autophagy in the pathogenesis of diabetic nephropathy. J Diabetes Res, 2013, 2013: 193757.
28.	Cao W, Li J, Yang K, et al. An overview of autophagy: mechanism, regulation and research progress. Bull Cancer, 2021, 108(3): 304-322.
29.	Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol, 2018, 19(2): 121-135.
30.	Jhanwar-Uniyal M, Wainwright JV, Mohan AL, et al. Diverse signaling mechanisms of mTOR complexes: mTORC1 and mTORC2 in forming a formidable relationship. Adv Biol Regul, 2019, 72: 51-62.
31.	Berliocchi L, Russo R, Maiarù M, et al. Autophagy impairment in a mouse model of neuropathic pain. Mol Pain, 2011, 7: 83.
32.	Berliocchi L, Maiarù M, Varano GP, et al. Spinal autophagy is differently modulated in distinct mouse models of neuropathic pain. Mol Pain, 2015, 11: 3.
33.	Shi CS, Shenderov K, Huang NN, et al. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol, 2012, 13(3): 255-263.
34.	Feng T, Yin Q, Weng ZL, Zhang JC, et al. Rapamycin ameliorates neuropathic pain by activating autophagy and inhibiting interleukin-1β in the rat spinal cord. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(6): 830-837.
35.	Feng XL, Deng HB, Wang ZG, et al. Suberoylanilide hydroxamic acid triggers autophagy by Influencing the mTOR pathway in the spinal dorsal horn in a rat neuropathic pain model. Neurochem Res, 2019, 44(2): 450-464.
36.	Li J, Tian M, Hua T, et al. Combination of autophagy and NFE2L2/NRF2 activation as a treatment approach for neuropathic pain. Autophagy, 2021, 17(12): 4062-4082.
37.	Pickles S, Vigié P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol, 2018, 28(4): R170-R185.
38.	Tong Y, Zhang XQ, Zhou HY. Chronic low back pain and sleep disturbance in adults in the US: the NHANES 2009-2010 study. Pain Physician, 2024, 27(2): E255-E262.
39.	Liu Y, Kuai S, Ding M, et al. Dexmedetomidine and ketamine attenuated neuropathic pain related behaviors via STING pathway to induce ER-phagy. Front Synaptic Neurosci, 2022, 14: 891803.
40.	Yu P, Zhang X, Liu N, et al. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther, 2021, 6(1): 128.
41.	Downs KP, Nguyen H, Dorfleutner A, et al. An overview of the non-canonical inflammasome. Mol Aspects Med, 2020, 76: 100924.
42.	Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature, 2016, 535(7610): 111-116.
43.	Orning P, Weng D, Starheim K, et al. Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death. Science, 2018, 362(6418): 1064-1069.
44.	Kayagaki N, Stowe IB, Lee BL, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature, 2015, 526(7575): 666-671.
45.	Chen R, Yin C, Fang J, et al. The NLRP3 inflammasome: an emerging therapeutic target for chronic pain. J Neuroinflammation, 2021, 18(1): 84.
46.	Li Z, Zhu J, Wang Y. ADAR3 alleviated inflammation and pyroptosis of neuropathic pain by targeting NLRP3 in chronic constriction injury mice. Gene, 2021, 805: 145909.
47.	Matikainen S, Nyman TA, Cypryk W. Function and regulation of noncanonical caspase-4/5/11 inflammasome. J Immunol, 2020, 204(12): 3063-3069.
48.	Zhou Y, Wang C, Si J, et al. Melatonin up-regulates bone marrow mesenchymal stem cells osteogenic action but suppresses their mediated osteoclastogenesis via MT2 -inactivated NF-κB pathway. Br J Pharmacol, 2020, 177(9): 2106-2122.
49.	Lee BL, Stowe IB, Gupta A, et al. Caspase-11 auto-proteolysis is crucial for noncanonical inflammasome activation. J Exp Med, 2018, 215(9): 2279-2288.
50.	Wu D, Zhang Y, Zhao C, et al. Disruption of C/EBPβ-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain. J Transl Med, 2022, 20(1): 583.
51.	Santa Cruz Garcia AB, Schnur KP, Malik AB, et al. Gasdermin D pores are dynamically regulated by local phosphoinositide circuitry. Nat Commun, 2022, 13(1): 52.
52.	Zhang D, Mao F, Wang S, et al. Role of transcription factor Nrf2 in pyroptosis in spinal cord injury by regulating GSDMD. Neurochem Res, 2023, 48(1): 172-187.
53.	Xue Q, Yan D, Chen X, et al. Copper-dependent autophagic degradation of GPX4 drives ferroptosis. Autophagy, 2023, 19(7): 1982-1996.
54.	Gao X, Gao LF, Zhang ZY, et al. miR-99b-3p/Mmp13 axis regulates NLRP3 inflammasome-dependent microglial pyroptosis and alleviates neuropathic pain via the promotion of autophagy. Int Immunopharmacol, 2024, 126: 111331.
55.	Chen LP, Gui XD, Tian WD, et al. Botulinum toxin type A-targeted SPP1 contributes to neuropathic pain by the activation of microglia pyroptosis. World J Psychiatry, 2024, 14(8): 1254-1266.
56.	Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol, 2021, 22(4): 266-282.
57.	Yang WS, Kim KJ, Gaschler MM, et al. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci U S A, 2016, 113(34): E4966-E4975.
58.	Dixon SJ, Winter GE, Musavi LS, et al. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem Biol, 2015, 10(7): 1604-1609.
59.	Chen X, Yu C, Kang R, et al. Cellular degradation systems in ferroptosis. Cell Death Differ, 2021, 28(4): 1135-1148.
60.	Bersuker K, Hendricks JM, Li Z, et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature, 2019, 575(7784): 688-692.
61.	Patil N, Walsh P, Carrabre K, et al. Regionally specific human pre-oligodendrocyte progenitor cells produce both oligodendrocytes and neurons after transplantation in a chronically injured spinal cord rat model after glial scar ablation. J Neurotrauma, 2021, 38(6): 777-788.
62.	Yan HF, Zou T, Tuo QZ, et al. Ferroptosis: mechanisms and links with diseases. Signal Transduct Target Ther, 2021, 6(1): 49.
63.	Li L, Guo L, Gao R, et al. Ferroptosis: a new regulatory mechanism in neuropathic pain. Front Aging Neurosci, 2023, 15: 1206851.
64.	Deng YF, Xiang P, Du JY, et al. Intrathecal liproxstatin-1 delivery inhibits ferroptosis and attenuates mechanical and thermal hypersensitivities in rats with complete Freund’s adjuvant-induced inflammatory pain. Neural Regen Res, 2023, 18(2): 456-462.
65.	Zhang W, Yu S, Jiao B, et al. Vitamin D₃ attenuates neuropathic pain via suppression of mitochondria-associated ferroptosis by inhibiting PKCα/NOX4 signaling pathway. CNS Neurosci Ther, 2024, 30(9): e70067.
66.	Tang J, Chen Q, Xiang L, et al. TRIM28 fosters microglia ferroptosis via autophagy modulation to enhance neuropathic pain and neuroinflammation. Mol Neurobiol, 2024, 61(11): 9459-9477.
67.	Guo Y, Du J, Xiao C, et al. Inhibition of ferroptosis-like cell death attenuates neuropathic pain reactions induced by peripheral nerve injury in rats. Eur J Pain, 2021, 25(6): 1227-1240.

1. Scholz J, Finnerup NB, Attal N, et al. The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain, 2019, 160(1): 53-59.
2. Chen O, Donnelly CR, Ji RR. Regulation of pain by neuro-immune interactions between macrophages and nociceptor sensory neurons. Curr Opin Neurobiol, 2020, 62: 17-25.
3. Gilron I, Baron R, Jensen T. Neuropathic pain: principles of diagnosis and treatment. Mayo Clin Proc, 2015, 90(4): 532-545.
4. Tang D, Kang R, Berghe TV, et al. The molecular machinery of regulated cell death. Cell Res, 2019, 29(5): 347-364.
5. Kowalski S, Karska J, Łapińska Z, et al. An overview of programmed cell death: apoptosis and pyroptosis-mechanisms, differences, and significance in organism physiology and pathophysiology. J Cell Biochem, 2023, 124(6): 765-784.
6. Vogeler S, Carboni S, Li X, et al. Phylogenetic analysis of the caspase family in bivalves: implications for programmed cell death, immune response and development. BMC Genomics, 2021, 22(1): 80.
7. Yang JK. Death effecter domain for the assembly of death-inducing signaling complex. Apoptosis, 2015, 20(2): 235-239.
8. Elena-Real CA, Díaz-Quintana A, González-Arzola K, et al. Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent apaf-1 inhibition. Cell Death Dis, 2018, 9(3): 365.
9. Erekat NS. Programmed cell death in cerebellar Purkinje neurons. J Integr Neurosci, 2022, 21(1): 30.
10. Dhuriya YK, Sharma D. Necroptosis: a regulated inflammatory mode of cell death. J Neuroinflammation, 2018, 15(1): 199.
11. Gradl G, Gaida S, Gierer P, et al. In vivo evidence for apoptosis, but not inflammation in the hindlimb muscle of neuropathic rats. Pain, 2004, 112(1/2): 121-130.
12. Sekiguchi M, Sekiguchi Y, Konno S, et al. Comparison of neuropathic pain and neuronal apoptosis following nerve root or spinal nerve compression. Eur Spine J, 2009, 18(12): 1978-1985.
13. Kaeidi A, Esmaeili-Mahani S, Sheibani V, et al. Olive (Olea europaea L. ) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies. J Ethnopharmacol, 2011, 136(1): 188-196.
14. Long Y, Liang F, Gao C, et al. Hyperbaric oxygen therapy reduces apoptosis after spinal cord injury in rats. Int J Clin Exp Med, 2014, 7(11): 4073-4081.
15. Dhani S, Zhao Y, Zhivotovsky B. A long way to go: caspase inhibitors in clinical use. Cell Death Dis, 2021, 12(10): 949.
16. Hyman BT, Yuan J. Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology. Nat Rev Neurosci, 2012, 13(6): 395-406.
17. Deng Y, Yang L, Xie Q, et al. Protein kinase A is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis. Mediators Inflamm, 2020, 2020: 6420425.
18. Liao MF, Yeh SR, Lu KT, et al. Interactions between autophagy, proinflammatory cytokines, and apoptosis in neuropathic pain: granulocyte colony stimulating factor as a multipotent therapy in rats with chronic constriction injury. Biomedicines, 2021, 9(5): 542.
19. Yu Z, Jiang N, Su W, et al. Necroptosis: a novel pathway in neuroinflammation. Front Pharmacol, 2021, 12: 701564.
20. Ohsumi Y. Historical landmarks of autophagy research. Cell Res, 2014, 24(1): 9-23.
21. Liang YX, Wang NN, Zhang ZY, et al. Necrostatin-1 ameliorates peripheral nerve injury-induced neuropathic pain by inhibiting the RIP1/RIP3 pathway. Front Cell Neurosci, 2019, 13: 211.
22. Duan Y, Li Q, Zhou Y, et al. Activation of the TNF-α-necroptosis pathway in parvalbumin-expressing interneurons of the anterior cingulate cortex contributes to neuropathic pain. Int J Mol Sci, 2023, 24(20): 15454.
23. Dong Yang M, Ming Jie W, Hui Zhou L, et al. Spinal microglial M1 polarization contributes paclitaxel-induced neuropathic pain by triggering cells necroptosis. J Biochem Mol Toxicol, 2024, 38(3): e23669.
24. Binshtok AM, Wang H, Zimmermann K, et al. Nociceptors are interleukin-1beta sensors. J Neurosci, 2008, 28(52): 14062-14073.
25. Yang Y, Klionsky DJ. Autophagy and disease: unanswered questions. Cell Death Differ, 2020, 27(3): 858-871.
26. Lahiri V, Hawkins WD, Klionsky DJ. Watch what you (self-) eat: autophagic mechanisms that modulate metabolism. Cell Metab, 2019, 29(4): 803-826.
27. Yamahara K, Yasuda M, Kume S, et al. The role of autophagy in the pathogenesis of diabetic nephropathy. J Diabetes Res, 2013, 2013: 193757.
28. Cao W, Li J, Yang K, et al. An overview of autophagy: mechanism, regulation and research progress. Bull Cancer, 2021, 108(3): 304-322.
29. Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol, 2018, 19(2): 121-135.
30. Jhanwar-Uniyal M, Wainwright JV, Mohan AL, et al. Diverse signaling mechanisms of mTOR complexes: mTORC1 and mTORC2 in forming a formidable relationship. Adv Biol Regul, 2019, 72: 51-62.
31. Berliocchi L, Russo R, Maiarù M, et al. Autophagy impairment in a mouse model of neuropathic pain. Mol Pain, 2011, 7: 83.
32. Berliocchi L, Maiarù M, Varano GP, et al. Spinal autophagy is differently modulated in distinct mouse models of neuropathic pain. Mol Pain, 2015, 11: 3.
33. Shi CS, Shenderov K, Huang NN, et al. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol, 2012, 13(3): 255-263.
34. Feng T, Yin Q, Weng ZL, Zhang JC, et al. Rapamycin ameliorates neuropathic pain by activating autophagy and inhibiting interleukin-1β in the rat spinal cord. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(6): 830-837.
35. Feng XL, Deng HB, Wang ZG, et al. Suberoylanilide hydroxamic acid triggers autophagy by Influencing the mTOR pathway in the spinal dorsal horn in a rat neuropathic pain model. Neurochem Res, 2019, 44(2): 450-464.
36. Li J, Tian M, Hua T, et al. Combination of autophagy and NFE2L2/NRF2 activation as a treatment approach for neuropathic pain. Autophagy, 2021, 17(12): 4062-4082.
37. Pickles S, Vigié P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol, 2018, 28(4): R170-R185.
38. Tong Y, Zhang XQ, Zhou HY. Chronic low back pain and sleep disturbance in adults in the US: the NHANES 2009-2010 study. Pain Physician, 2024, 27(2): E255-E262.
39. Liu Y, Kuai S, Ding M, et al. Dexmedetomidine and ketamine attenuated neuropathic pain related behaviors via STING pathway to induce ER-phagy. Front Synaptic Neurosci, 2022, 14: 891803.
40. Yu P, Zhang X, Liu N, et al. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther, 2021, 6(1): 128.
41. Downs KP, Nguyen H, Dorfleutner A, et al. An overview of the non-canonical inflammasome. Mol Aspects Med, 2020, 76: 100924.
42. Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature, 2016, 535(7610): 111-116.
43. Orning P, Weng D, Starheim K, et al. Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death. Science, 2018, 362(6418): 1064-1069.
44. Kayagaki N, Stowe IB, Lee BL, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature, 2015, 526(7575): 666-671.
45. Chen R, Yin C, Fang J, et al. The NLRP3 inflammasome: an emerging therapeutic target for chronic pain. J Neuroinflammation, 2021, 18(1): 84.
46. Li Z, Zhu J, Wang Y. ADAR3 alleviated inflammation and pyroptosis of neuropathic pain by targeting NLRP3 in chronic constriction injury mice. Gene, 2021, 805: 145909.
47. Matikainen S, Nyman TA, Cypryk W. Function and regulation of noncanonical caspase-4/5/11 inflammasome. J Immunol, 2020, 204(12): 3063-3069.
48. Zhou Y, Wang C, Si J, et al. Melatonin up-regulates bone marrow mesenchymal stem cells osteogenic action but suppresses their mediated osteoclastogenesis via MT2 -inactivated NF-κB pathway. Br J Pharmacol, 2020, 177(9): 2106-2122.
49. Lee BL, Stowe IB, Gupta A, et al. Caspase-11 auto-proteolysis is crucial for noncanonical inflammasome activation. J Exp Med, 2018, 215(9): 2279-2288.
50. Wu D, Zhang Y, Zhao C, et al. Disruption of C/EBPβ-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain. J Transl Med, 2022, 20(1): 583.
51. Santa Cruz Garcia AB, Schnur KP, Malik AB, et al. Gasdermin D pores are dynamically regulated by local phosphoinositide circuitry. Nat Commun, 2022, 13(1): 52.
52. Zhang D, Mao F, Wang S, et al. Role of transcription factor Nrf2 in pyroptosis in spinal cord injury by regulating GSDMD. Neurochem Res, 2023, 48(1): 172-187.
53. Xue Q, Yan D, Chen X, et al. Copper-dependent autophagic degradation of GPX4 drives ferroptosis. Autophagy, 2023, 19(7): 1982-1996.
54. Gao X, Gao LF, Zhang ZY, et al. miR-99b-3p/Mmp13 axis regulates NLRP3 inflammasome-dependent microglial pyroptosis and alleviates neuropathic pain via the promotion of autophagy. Int Immunopharmacol, 2024, 126: 111331.
55. Chen LP, Gui XD, Tian WD, et al. Botulinum toxin type A-targeted SPP1 contributes to neuropathic pain by the activation of microglia pyroptosis. World J Psychiatry, 2024, 14(8): 1254-1266.
56. Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol, 2021, 22(4): 266-282.
57. Yang WS, Kim KJ, Gaschler MM, et al. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci U S A, 2016, 113(34): E4966-E4975.
58. Dixon SJ, Winter GE, Musavi LS, et al. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem Biol, 2015, 10(7): 1604-1609.
59. Chen X, Yu C, Kang R, et al. Cellular degradation systems in ferroptosis. Cell Death Differ, 2021, 28(4): 1135-1148.
60. Bersuker K, Hendricks JM, Li Z, et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature, 2019, 575(7784): 688-692.
61. Patil N, Walsh P, Carrabre K, et al. Regionally specific human pre-oligodendrocyte progenitor cells produce both oligodendrocytes and neurons after transplantation in a chronically injured spinal cord rat model after glial scar ablation. J Neurotrauma, 2021, 38(6): 777-788.
62. Yan HF, Zou T, Tuo QZ, et al. Ferroptosis: mechanisms and links with diseases. Signal Transduct Target Ther, 2021, 6(1): 49.
63. Li L, Guo L, Gao R, et al. Ferroptosis: a new regulatory mechanism in neuropathic pain. Front Aging Neurosci, 2023, 15: 1206851.
64. Deng YF, Xiang P, Du JY, et al. Intrathecal liproxstatin-1 delivery inhibits ferroptosis and attenuates mechanical and thermal hypersensitivities in rats with complete Freund’s adjuvant-induced inflammatory pain. Neural Regen Res, 2023, 18(2): 456-462.
65. Zhang W, Yu S, Jiao B, et al. Vitamin D₃ attenuates neuropathic pain via suppression of mitochondria-associated ferroptosis by inhibiting PKCα/NOX4 signaling pathway. CNS Neurosci Ther, 2024, 30(9): e70067.
66. Tang J, Chen Q, Xiang L, et al. TRIM28 fosters microglia ferroptosis via autophagy modulation to enhance neuropathic pain and neuroinflammation. Mol Neurobiol, 2024, 61(11): 9459-9477.
67. Guo Y, Du J, Xiao C, et al. Inhibition of ferroptosis-like cell death attenuates neuropathic pain reactions induced by peripheral nerve injury in rats. Eur J Pain, 2021, 25(6): 1227-1240.

West China Medical Journal

Research progress on the role of programmed cell death in the mechanism of neuropathic pain

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