ArticleBioelectronic medicine2022
High-frequency electrical stimulation attenuates neuronal release of inflammatory mediators and ameliorates neuropathic pain.
Article in Bioelectronic medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 14 citations in OpenAlex.
- Noninvasive Bioelectronic Treatment of Postcesarean Pain: A Randomized Clinical Trial.JAMA network open · 2023Trial
- The analgesic effect of electroacupuncture in alleviating paclitaxel-induced peripheral neuropathic pain and its possible mechanism relates to TLR4/P2X7-NLRP3 signaling pathway.Purinergic signalling · 2026Article
- Temporal regulation of macrophage polarization by abnormally innervated CGRP + Sensory nerves following spinal cord injury.Cellular and molecular life sciences : CMLS · 2026Review
- The neuroimmune microenvironment of peripheral nerve injury: mechanisms, pathophysiology, and therapeutic implications.Frontiers in surgery · 2026Review
- Nociceptor α7nAChR activation blunts neuronal HMGB1 release and attenuates inflammation and nociceptive behavior.Molecular medicine (Cambridge, Mass.) · 2025Article
- Advances in sciatic nerve regeneration: A review of contemporary techniques.Regenerative therapy · 2025Review
- Advancements in stimulation therapies for peripheral nerve regeneration.Biomedical materials (Bristol, England) · 2024Review
- A Narrative Review of the Dorsal Root Ganglia and Spinal Cord Mechanisms of Action of Neuromodulation Therapies in Neuropathic Pain.Brain sciences · 2024Review
- Modulating pro-adhesive nature of metallic surfaces through a polypeptide coupling via diazonium chemistry.Scientific reports · 2023Article
- Neuroinflammation in the Evolution of Motor Function in Stroke and Trauma Patients: Treatment and Potential Biomarkers.Current issues in molecular biology · 2023Review
- Hmgb1 Silencing in the Amygdala Inhibits Pain-Related Behaviors in a Rat Model of Neuropathic Pain.International journal of molecular sciences · 2023Article
- High frequency alternating current neurostimulation decreases nocifensive behavior in a disc herniation model of lumbar radiculopathy.Bioelectronic medicine · 2023Article
- Article
- Application of transcutaneous electrical nerve stimulation (TENS) for restoring sexual function after gender-affirming genital reconstruction: a hypothesis.Therapeutic advances in urologyReview
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundNeuroinflammation is an important driver of acute and chronic pain states. Therefore, targeting molecular mediators of neuroinflammation may present an opportunity for developing novel pain therapies. In preclinical models of neuroinflammatory pain, calcitonin gene-related peptide (CGRP), substance P and high mobility group box 1 protein (HMGB1) are molecules synthesized and released by sensory neurons which activate inflammation and pain. High-frequency electrical nerve stimulation (HFES) has achieved clinical success as an analgesic modality, but the underlying mechanism is unknown. Here, we reasoned that HFES inhibits neuroinflammatory mediator release by sensory neurons to reduce pain.
methodsUtilizing in vitro and in vivo assays, we assessed the modulating effects of HFES on neuroinflammatory mediator release by activated sensory neurons. Dorsal root ganglia (DRG) neurons harvested from wildtype or transgenic mice expressing channelrhodopsin-2 (ChR2) were cultured on micro-electrode arrays, and effect of HFES on optogenetic- or capsaicin-induced neuroinflammatory mediator release was determined. Additionally, the effects of HFES on local neuroinflammatory mediator release and hyperalgesia was assessed in vivo using optogenetic paw stimulation and the neuropathic pain model of chronic constriction injury (CCI) of the sciatic nerve.
resultsLight- or capsaicin-evoked neuroinflammatory mediator release from cultured transgenic DRG sensory neurons was significantly reduced by concurrent HFES (10 kHz). In agreement with these findings, elevated levels of neuroinflammatory mediators were detected in the affected paw following optogenetic stimulation or CCI and were significantly attenuated using HFES (20.6 kHz for 10 min) delivered once daily for 3 days.
conclusionThese studies reveal a previously unidentified mechanism for the pain-modulating effect of HFES in the setting of acute and chronic nerve injury. The results support the mechanistic insight that HFES may reset sensory neurons into a less pro-inflammatory state via inhibiting the release of neuroinflammatory mediators resulting in reduced inflammation and pain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.