Table 3.
Summary of trails about different electrical stimulation sites for PNI
| Study | Paradigm frequency/pulse width/pulse form/time/threshold | Nerve injury condition | Function/mechanism | Stimulation site | The type of study | Main viewpoints and guidance significance |
|---|---|---|---|---|---|---|
| Pei et al., 2015 | 15 Hz/NM*/NM*/30 min/6.5 mA | Sciatic nerve transection injury and its proximal and distal ends were inverted and sutured | Protects sensory neurons and anterior horn | Placed in the epidural space of spinal cord (T10 and L3) | Animal experiments | ES of the neuronal cell bodies can protect motor and sensory neurons in spinal cord after PNI. In addition, it promotes the regeneration of myelinated nerve fibers to repair injured peripheral nerve. |
| Tilley et al., 2016 | 50 Hz/NM*/charge-balanced square pulse/72 h/70% motor threshold, 0.3–10 mA. | Tibial and common peroneal nerves distal injury | cFOS and 5HT3ra and GABAbr1/ attenuate the neuroinflammatory response to relieve pain | Epidural space of spinal cord (L1–L5) | Animal experiments | SCS could relieve pain after PNI by regulation of relevant ion channels and gene expression. |
| Willand et al., 2016 | 100 Hz/ 200–400 μs/charge balanced/1 h/visible muscle contraction, 2–3 mA | Tibial nerve transection injury; immediate repair | Elevated muscle-derived GDNF | Implanted in the gastrocnemius muscle | Animal experiments | The levels of nutrient factor mRNA were increased and peripheral nerve regeneration was promoted by targeting ES of skeletal muscle. |
| Jiang et al., 2018 | 20 Hz/0.1 ms/NM*/1 h/0.3 mA, subthreshold | Ensory and motor branches of the pudendal nerve bilaterally; crush injury | Neuro regeneration through upregulating BDNF and βII-tubulin | Pudendal nerve | Animal experiments | ES of pudendal nerve can promote neuroregenerative response by upregulating BDNF to promote neuromuscular continence mechanism recovery. |
| Mendez et al., 2018 | 20 Hz/100 μs/NM*/1 h/1.5 mA, right ear flutter | Facial nerve crush injury | Improved facial nerve specific pathway regeneration | Facial nerve | Animal experiments | This is the first study to apply an implantable device to BES for facial nerve injury, accelerating functional recovery and induction of motor neuronal path-specific regeneration. |
| Nicolas et al., 2018 | 60 Hz/250 μs/NM*/15 min/3 V | Sciatic nerve transection injury; implementation of microsurgical epineural sutures | Nerve regeneration and muscle reinnervation | Epidural space of motor cortex in the brain | Animal experiments | ES of the motor cortex induces a higher rate of nerve re-innervation and a faster functional recovery than electrical stimulation of peripheral nerves after PNI. |
| Senger et al., 2018 | 20 Hz/0.1 ms/balanced biphasic pulses/1 h | Common peroneal nerve transection injury; sutured with a two-layer closure | RAG/increased the length of nerve regeneration and regenerating axons | Common peroneal nerve | Animal experiments | It is the first time to apply conditioning ES to an in vivo model of peripheral nerve regeneration. Findings from this study demonstrate that this treatment strategy accelerates nerve regeneration. |
| Senger et al., 2019 | 20 Hz/0.1 ms/balanced biphasic pulses/1 h/visible twitch in the lower limb flexors | Tibial nerve transection injury; immediate microsurgical repair surgery | Neuro regeneration and functional recovery | Tibial nerve | Animal experiments | Conditioning ES can promote the regeneration of target nerves and the recovery of functional activity, which can be given preoperatively. |
| Fu et al., 2020 | 100 Hz/200 μs/on: off = 1:2/30 min/visible toe and foot movement | Sciatic nerve transection injury; implementation of repair surgery | Axon regeneration through promoting autophagy flux in the distal nerve segments | Skin | Animal experiments | ES of denervated muscle can increase cell autophagy flux level in the nerve distal to injury, which is conducive to nerve regeneration. |
5HT3ra: 5-Hydroxytryptamine (serotonin) receptor 3a; BDNF: brain-derived neurotrophic factor; BES: brief electrical stimulation; cFOS: c FBJ osteosarcoma oncogene; ES: electrical stimulation; GABAbr1: γ-aminobutyric acid B receptor 1; GDNF: glial cell line-derived neurotrophic factor; NM*: not mentioned in the text; PNI: peripheral nerve injury; RAG: regeneration-associated gene; SCS: spinal cord stimulation.