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Cited by 164Nerve injury and regenerationNerve Injury and RehabilitationNeuroscience and Neural Engineering

The DOI matches its Crossref record; 122 of the 122 references it cites were found in a registry or an index.

Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

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Chu, Xiao-Lei, Song, Xi-Zi, Li, Qi, Li, Yu-Ru, He, Feng, Gu, Xiao-Song, Ming, Dong·2022·Neural Regeneration Research
DOI 10.4103/1673-5374.335823PMC PMC9083151
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Abstract

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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Crossref · 10.4103/1673-5374.335823

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Figures

Figure 1 Electrical stimulation elevates peripheral nerve regeneration-associated genes within the neuronal cell body. ES increased brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB), which upregulates the expression of cyclic AMP (cAMP) through a Ca2+-dependent mechanism. The signal Ras-mitogen activated protein kinase (Ras/MAPK) pathway, which is essential for the neurophin-induced differentiation of neuronal cells, is activated by BDNF as well. Ras, which is stimulated by the trkB receptor, also causes activation of kinases phosphatidylinositol 3-kinase/Akt (PI3K/Akt). The different neurotrophin signaling pathways activated by cAMP response element-binding protein (CREB) converge at the level of transcription in the nucleus. CREB induces increased expression of regeneration-associated genes such as growth-associated protein-43 (GAP-43), which promotes axonal sprouting and prevents growth cone collapse, and Tα1 tubulin, which is an integral protein for cytoskeletal assembly. See the text in the section “Staggered axonal regeneration” for a detailed description.
Figure 1 Electrical stimulation elevates peripheral nerve regeneration-associated genes within the neuronal cell body. ES increased brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB), which upregulates the expression of cyclic AMP (cAMP) through a Ca2+-dependent mechanism. The signal Ras-mitogen activated protein kinase (Ras/MAPK) pathway, which is essential for the neurophin-induced differentiation of neuronal cells, is activated by BDNF as well. Ras, which is stimulated by the trkB receptor, also causes activation of kinases phosphatidylinositol 3-kinase/Akt (PI3K/Akt). The different neurotrophin signaling pathways activated by cAMP response element-binding protein (CREB) converge at the level of transcription in the nucleus. CREB induces increased expression of regeneration-associated genes such as growth-associated protein-43 (GAP-43), which promotes axonal sprouting and prevents growth cone collapse, and Tα1 tubulin, which is an integral protein for cytoskeletal assembly. See the text in the section “Staggered axonal regeneration” for a detailed description.CC BY-NC-SA · PubMed Central
Figure 2 Following PNI, several molecular and cellular changes are observed at the local site of injury and the target organs. The effects of ES therapy on peripheral neurogenesis vary according to the position of stimulation. See the text for a detailed description. DRG: Dorsal root ganglion; ES: electrical stimulation; PNI: peripheral nerve injury; SCs: Schwann cells; SDH: spinal cord dorsal horn; SQS: subcutaneous electrical stimulation; SVH: spinal cord ventral horn.
Figure 2 Following PNI, several molecular and cellular changes are observed at the local site of injury and the target organs. The effects of ES therapy on peripheral neurogenesis vary according to the position of stimulation. See the text for a detailed description. DRG: Dorsal root ganglion; ES: electrical stimulation; PNI: peripheral nerve injury; SCs: Schwann cells; SDH: spinal cord dorsal horn; SQS: subcutaneous electrical stimulation; SVH: spinal cord ventral horn.CC BY-NC-SA · PubMed Central

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Research works printed but not linked: 1

  1. Gybels, 1990, The treatment of pain due to peripheral-nerve injury by electrical-stimulitation of the injured nerve, Adv Pain Res Ther, 13, 217

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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
ORCID
Venue
Neural Regeneration Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-02-28
Volume
17
Issue
10
Pages
2185-2193
ISSN
  • 1673-5374 (ISSN-L)
  • 1876-7958
DOI
10.4103/1673-5374.335823
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
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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