Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury
Background and aim: Neuropathic pain (NP), caused by nerve injury or dysfunction, poses a significant clinical challenge due to its limited response to conventional pharmacological treatments. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive neuromodulatory...
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Elsevier
2025-07-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025001959 |
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| author | Tianying Li Guanwen Lin Tao Zhang Yani Guo Yongjin He Jing Luan Jin Wang Dan Lyu Yiqi Weng Xin Jin |
| author_facet | Tianying Li Guanwen Lin Tao Zhang Yani Guo Yongjin He Jing Luan Jin Wang Dan Lyu Yiqi Weng Xin Jin |
| author_sort | Tianying Li |
| collection | DOAJ |
| description | Background and aim: Neuropathic pain (NP), caused by nerve injury or dysfunction, poses a significant clinical challenge due to its limited response to conventional pharmacological treatments. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive neuromodulatory approach for NP management. This study aimed to evaluate the therapeutic efficacy of rTMS in alleviating NP induced by chronic constriction injury (CCI) in a mouse model and to investigate the underlying molecular mechanisms through transcriptomic profiling. Procedures: Adult male mice underwent CCI surgery to induce NP and were randomly assigned to receive either rTMS (5 Hz or 10 Hz) or sham stimulation. rTMS was applied once daily for 14 consecutive days, beginning on postoperative day 7. Behavioral assessments—including paw withdrawal latency (PWL) and paw withdrawal threshold (PWT)—were conducted to evaluate thermal hyperalgesia and mechanical allodynia, respectively. Anxiety-like behaviors were assessed using the open field test (OFT) and elevated plus maze (EPM). At the end of the treatment period, brain tissues were harvested for RNA sequencing and differentially expressed genes (DEGs) were identified and analyzed. Results and conclusion: rTMS at both 5 Hz and 10 Hz significantly improved PWL and PWT in CCI mice and reduced anxiety-like behaviors. Transcriptomic analysis revealed that CCI induced dysregulation of 66 genes, while rTMS partially normalized gene expression patterns. Functional enrichment analysis indicated significant involvement of pathways related to inflammatory responses, transporter activity, and ion channel regulation. These findings support the potential of rTMS as a multifaceted, non-invasive therapeutic strategy for neuropathic pain, with molecular mechanisms likely involving modulation of neuroinflammatory and neuroexcitatory pathways. |
| format | Article |
| id | doaj-art-ff293faffd8a44d4a6432bcf1cbf13fb |
| institution | OA Journals |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-ff293faffd8a44d4a6432bcf1cbf13fb2025-08-20T02:31:33ZengElsevierBrain Research Bulletin1873-27472025-07-0122711138310.1016/j.brainresbull.2025.111383Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injuryTianying Li0Guanwen Lin1Tao Zhang2Yani Guo3Yongjin He4Jing Luan5Jin Wang6Dan Lyu7Yiqi Weng8Xin Jin9School of Medicine, Nankai University, Tianjin, ChinaDepartment of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaSchool of Public Health, Gansu University of Chinese Medicine, Lanzhou, ChinaDepartment of Pain, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Pain, Tianjin First Central Hospital, Tianjin, ChinaOutpatient Department, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Pain, Tianjin First Central Hospital, Tianjin, China; Corresponding authors.Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China; Corresponding authors.School of Medicine, Nankai University, Tianjin, China; Corresponding authors.Background and aim: Neuropathic pain (NP), caused by nerve injury or dysfunction, poses a significant clinical challenge due to its limited response to conventional pharmacological treatments. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive neuromodulatory approach for NP management. This study aimed to evaluate the therapeutic efficacy of rTMS in alleviating NP induced by chronic constriction injury (CCI) in a mouse model and to investigate the underlying molecular mechanisms through transcriptomic profiling. Procedures: Adult male mice underwent CCI surgery to induce NP and were randomly assigned to receive either rTMS (5 Hz or 10 Hz) or sham stimulation. rTMS was applied once daily for 14 consecutive days, beginning on postoperative day 7. Behavioral assessments—including paw withdrawal latency (PWL) and paw withdrawal threshold (PWT)—were conducted to evaluate thermal hyperalgesia and mechanical allodynia, respectively. Anxiety-like behaviors were assessed using the open field test (OFT) and elevated plus maze (EPM). At the end of the treatment period, brain tissues were harvested for RNA sequencing and differentially expressed genes (DEGs) were identified and analyzed. Results and conclusion: rTMS at both 5 Hz and 10 Hz significantly improved PWL and PWT in CCI mice and reduced anxiety-like behaviors. Transcriptomic analysis revealed that CCI induced dysregulation of 66 genes, while rTMS partially normalized gene expression patterns. Functional enrichment analysis indicated significant involvement of pathways related to inflammatory responses, transporter activity, and ion channel regulation. These findings support the potential of rTMS as a multifaceted, non-invasive therapeutic strategy for neuropathic pain, with molecular mechanisms likely involving modulation of neuroinflammatory and neuroexcitatory pathways.http://www.sciencedirect.com/science/article/pii/S0361923025001959Repetitive transcranial magnetic stimulationBehaviorBrain transcriptomeChronic constriction injury |
| spellingShingle | Tianying Li Guanwen Lin Tao Zhang Yani Guo Yongjin He Jing Luan Jin Wang Dan Lyu Yiqi Weng Xin Jin Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury Brain Research Bulletin Repetitive transcranial magnetic stimulation Behavior Brain transcriptome Chronic constriction injury |
| title | Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury |
| title_full | Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury |
| title_fullStr | Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury |
| title_full_unstemmed | Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury |
| title_short | Repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury |
| title_sort | repetitive transcranial magnetic stimulation ameliorates chronic pain behavior and modulates the brain transcriptome in a mouse model of chronic constriction injury |
| topic | Repetitive transcranial magnetic stimulation Behavior Brain transcriptome Chronic constriction injury |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025001959 |
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