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Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation
Open accessAbstract
Previous studies on the mechanisms of peripheral nerve injury (PNI) have mainly focused on the pathophysiological changes within a single injury site. However, recent studies have indicated that within the central nervous system, PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels. Therefore, the basic mechanisms of PNI have not been comprehensively understood. Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI, as well as to alleviate neuropathic pain, the specific mechanisms of successful PNI treatment are unclear. We summarize and discuss the basic mechanisms of PNI and of treatment via electrical stimulation. After PNI, activity in the central nervous system (spinal cord) is altered, which can limit regeneration of the damaged nerve. For example, cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration. The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI. This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. A slow speed of axon regeneration leads to low nerve regeneration. Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration. Electrical stimulation of target organs can reduce the atrophy of denervated skeletal muscle and promote the recovery of sensory function. Findings from the included studies confirm that after PNI, a series of physiological and pathological changes occur in the spinal cord, injury site, and target organs, leading to dysfunction. Electrical stimulation may address the pathophysiological changes mentioned above, thus promoting nerve regeneration and ameliorating dysfunction.
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“However, peripheral nerves have the potential to self-repair and regenerate, aided by conditions such as anatomical continuity of the injured site, myelination, and the extent of the injury [112].”
From Active Neural Interface Circuits and Systems for Selective Control of Peripheral Nerves: A Review (2024) · cites this paper as [112]
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“Moreover, various forms of physical stimulation are ben-eficial for promoting the recovery of sensory function, such as electric stimulation [24], magnetic stimulation [25], ultrasonic stimulation [26], and laser therapy [27].”
Current Treatments and Future Directions for Facial Paralysis
Leckenby, J. I., Sweitzer, K. R., Olsen, T. C., Mayorga-Young, D., Milek, D., & Grobbelaar, A. O. (2024) · Facial Plastic Surgery · doi:10.1055/a-2358-9401 · Cited by 6
“69,70,78 Recent clinical trials have revealed signi fi cant potential for ES in human subjects.”
Exogenous Antioxidants in Remyelination and Skeletal Muscle Recovery
Cabezas-Pérez, R., Ávila-Rodriguez, M., & Salazar, D. H. R. (2022) · Biomedicines · doi:10.3390/biomedicines10102557 · Cited by 6
Wireless Battery‐Free Peripheral Nerve Stimulation Conch for Remote Muscle Activation
Mingwang, Z., Yang, G., Long, Z., Tang, Y. C., Li, D., Liang, S., Lin, R., Yang, Z., Bao, H., Xing, L., et al. (2023) · Advanced Materials Technologies · doi:10.1002/admt.202301458 · Cited by 6
Stem cell therapy: A promising therapeutic approach for skeletal muscle atrophy
Wang, Y., Chen, Z., Shen, Y., Wang, K., Han, Y.-M., Zhang, C., Yang, X.-M., & Chen, B. (2025) · World Journal of Stem Cells · doi:10.4252/wjsc.v17.i2.98693 · Cited by 6
“In addition, denervation-induced muscular atrophy is likewise associated with the diminished availability of neurotrophic factors and lowered levels of activity[25].”
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Transcutaneous electrotherapy of facial nerve injuries based on dissolvable conductive microneedles
Lin, L., Yuan, X., Ma, L., Xu, L., Xie, W., Jiang, Y., Xiu, J., Xu, H., Tian, Z., Qu, J., et al. (2025) · Bioactive Materials · doi:10.1016/j.bioactmat.2025.07.013 · Cited by 5
“So far, some therapeutic approaches are available for facial nerve injury, including surgical intervention, pharmacotherapy ( e.g. , calcium-channel blocker, immunosuppressant, glucocorticoid), [19 – 21], and physical therapy [22,23].”
Targeted therapy: P2X3 receptor silencing in bone cancer pain relief
Jiang, Y., Liu, X., Zhang, H., & Xu, L. (2024) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.70026 · Cited by 5
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“This neuroinflammatory environment enhances neuronal excitability and synaptic plasticity, thereby lowering the seizure threshold and increasing the risk of seizure occurrence [52].”
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“Multiple studies and review articles have cited cAMP as a key player in the mechanism of PES [65–68, 71, 73, 75–78]; this conclusion, however, is based on studies confirming brain-derived neurotrophic factor (BDNF) as a mediator of the PES effect [7, 36, 46–48, 55, 66, 70, 79–83].”
Peripheral nerve repair: innovations and future directions
Aldali, F., 唐莉, Yang, Y., Huang, Y., Li, Y., Deng, C., & Chen, H. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-025-07567-z · Cited by 5
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Delayed repair of the facial nerve and its negative impacts on nerve and muscle regeneration
Bueno, C. R. D. S., Buchaim, D. V., Barraviera, B., Ferreira, R. S., Santos, P. S. D. S., Reis, C. H. B., Cini, M. A., Kuga, M. C., Rosa, G. M., & Buchaim, R. L. (2024) · The Journal of venomous animals and toxins including tropical diseases · doi:10.1590/1678-9199-jvatitd-2023-0093 · Cited by 4
Yu, F., Qi, T., Yuan, Y., Weng, J., Wang, T., Kou, Y., & Zeng, H. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2308157 · Cited by 4
A Systematic Review of Registered Clinical Trials for Peripheral Nerve Injuries
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Akkoca, A., Gültekin, B., Şen, A., & Kutlu, S. (2025) · Scientific Reports · doi:10.1038/s41598-025-21500-w · Cited by 3
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Chen, X., Gao, R., Liang, X., Liu, K. J. R., Wei, Z., Wu, X., Goto, T., Xiong, C., Xu, F., & Dai, H. (2026) · Regenerative Biomaterials · doi:10.1093/rb/rbag068 · Cited by 3
Huang, Y., Gong, Y., Liu, Y., & Lü, J.-Q. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.991099 · Cited by 4
“This phenomenon may limit practical applications because NMES tends to cause muscle fatigue (73).”
BackgroundInfluentialClinical Approach to Chronic Pain due to Perioperative Nerve Injury
Terkawi, A. S., Altirkawi, O. K., Salmasi, V., & Ottestad, E. (2023) · Anesthesiology Clinics · doi:10.1016/j.anclin.2023.03.009 · Cited by 3
Zhang, Y., Zhao, X., Liu, M., Zhou, Z., Cheng, H.-B., Jiang, X., Zheng, Y., & Chen, Z. (2025) · Journal of Chinese Integrative Medicine · doi:10.1016/j.joim.2025.03.001 · Cited by 2
Raasveld, F. V., Johnston, B. R., Hao, D., Valerio, I. L., & Eberlin, K. R. (2025) · Microsurgery · doi:10.1002/micr.70112 · Cited by 2
Electroactive biomaterials in neural regeneration: Advances and therapeutic mechanisms
Diao, S., Liu, X., Li, Z., Zhu, S., Yuan, J., Liu, F., Lu, X., Luo, H., Farooq, U., Wu, J., et al. (2025) · Chinese Chemical Letters · doi:10.1016/j.cclet.2025.112205 · Cited by 2
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Emerick, T. D., Vorenkamp, K. E., Francio, V. T., Srinivasan, S. S., Singla, P., Castellanos, J. P., Ahadian, F. M., Chen, Z., Gianlorenco, A. L., Sarno, D. L., et al. (2026) · Pain Medicine · doi:10.1093/pm/pnag076 · Cited by 2
“121 Electrical stimulation modalities such as FES and tSCS are used to reduce spasticity and enhance motor control.”
Petrova, E. S., & Kolos, E. A. (2023) · CLINICAL AND EXPERIMENTAL MORPHOLOGY · doi:10.31088/cem2023.12.4.62-70 · Cited by 2
Metadata
- Authors
- Chu, X.-L., Song, X.-Z., Li, Q., Li, Y.-R., He, F., Gu, X.-S., & Ming, D.
- Affiliations
- Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
- Tianjin University (CN)
- Tianjin University of Sport (CN)
- Corresponding author
- He, Feng
- Gu, Xiao-Song
- Venue
- Neural Regeneration Research
- Published
- 2022-02-28
- Volume
- 17
- Issue
- 10
- Pages
- 2185-2193
- ISSN
- 1673-5374 (ISSN-L)
- 1876-7958
- PMC
- PMC9083151
- OpenAlex
- W4220934018
- Cited by
- 164
- References
- 122
- Citations by year
- 2026: 46 · 2025: 47 · 2024: 40 · 2023: 20 · 2022: 11
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- Neural Regeneration Research (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Surgery › Nerve Injury and Rehabilitation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Keywords
- peripheral nerve injury, electrical stimulation, axon regeneration, neuropathic pain, spinal cord, synaptic stripping, dorsal root ganglia, ectopic discharges, denervation, skeletal muscle atrophy, hyperalgesia, functional rehabilitation, target organs
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