Exploring the vagus nerve and the inflammatory reflex for therapeutic benefit in chronic spinal cord injury

Bloom, Ona; Tracey, Kevin J.; Pavlov, Valentin A.

doi:10.1097/wco.0000000000001036

Cited by 4 publications

(3 citation statements)

References 90 publications

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“…Secondly, the use of a single mouse model may restrict the generalizability of the findings. It would be beneficial to replicate the results in other mouse models, larger animal models, and investigate the effects of Ccl2 depletion on other aspects of SCI, such as inflammation and neuronal damage ( 32 ). Although the ttw mouse model used in this study is a valuable tool for investigating chronic spinal compression, it is a genetic model and may not fully replicate the etiology of chronic spinal compression caused by SCI in humans ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression

Yang

Wang

et al. 2023

Front. Immunol.

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IntroductionChronic spinal compression is a common complication of spinal cord injury (SCI), which can lead to spinal stenosis or herniated discs. The ensuing neuropathic pain is often associated with the activation of microglia. In this investigation, our objective was to explore whether modifying the levels of chemokine (C-C motif) ligand 2 (Ccl2) in microglia could alleviate neuropathic pain resulting from chronic spinal compression.MethodsWe used a public database to look for major altered gene associated in a SCI model established in rats. We then employed adeno-associated virus (AAV) vectors, expressing siRNA for the identified significantly altered gene under a microglia-specific TMEM119 promoter. We also tested the impact of this treatment in microglia in vivo on the severity of chronic spinal compression and associated pain using a ttw mouse model for progressive spinal compression.ResultsWe identified chemokine (C-C motif) ligand 2 (Ccl2) as the primary gene altered in microglia within a rat SCI model, utilizing a public database. Microglial Ccl2 levels were then found to be significantly elevated in disc specimens from SCI patients diagnosed with chronic spinal compression and strongly correlated with the Thompson classification of the degeneration level and pain score. Depletion of Ccl2 in microglia-specific TMEM119 promoter were developed to transfect mouse microglia in vitro, resulting in a proinflammatory to anti-inflammatory phenotypic adaption. In vivo depletion of Ccl2 in microglia mitigated the severity of chronic spinal compression and related pain in ttw mice, likely due to significant changes in pain-associated cytokines and factors.ConclusionDisc microglia expressing high levels of Ccl2 may contribute to chronic spinal compression and SCI-associated pain. Therapeutically targeting Ccl2 in microglia could offer a potential avenue for treating chronic spinal compression and SCI-associated pain.

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Section: Discussionmentioning

confidence: 99%

Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression

Yang

Wang

et al. 2023

Front. Immunol.

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“…Vagus nerve stimulation (VNS), through a device similar to a pacemaker, stimulates the vagus nerve through regular electrical pulses that ultimately reach the brain. Although only U.S Food and Drug Administration (FDA)-approved for treatment-resistant epilepsy and depression, recent exploration for its use in post-stroke recovery has laid the foundation for a similar use in the SCI population ( 109 ). Clinical findings demonstrate pairing VNS with rehabilitation therapy facilitates synaptic plasticity in spared networks and improvement in post-stroke motor recovery ( 110 , 111 ).…”

Section: Modalitiesmentioning

confidence: 99%

Narrative review of current neuromodulation modalities for spinal cord injury

Medina

Reddy

et al. 2023

Front. Pain Res.

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Neuromodulation is a developing field of medicine that includes a vast array of minimally invasive and non-invasive therapies including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), peripheral nerve stimulation, and spinal cord stimulation (SCS). Although the current literature surrounding the use of neuromodulation in managing chronic pain is abundant, there is an insufficient amount of evidence specifically regarding neuromodulation in patients with spinal cord injury (SCI). Given the pain and functional deficits that these patients face, that are not amenable to other forms conservative therapy, the purpose of this narrative review is to examine and assess the use of various neuromodulation modalities to manage pain and restore function in the SCI population. Currently, high-frequency spinal cord stimulation (HF-SCS) and burst spinal cord stimulation (B-SCS) have been shown to have the most promising effect in improving pain intensity and frequency. Additionally, dorsal root ganglion stimulation (DRG-S) and TMS have been shown to effectively increase motor responses and improve limb strength. Although these modalities carry the potential to enhance overall functionality and improve a patient's degree of disability, there is a lack of long-term, randomized-controlled trials in the current space. Additional research is warranted to further support the clinical use of these emerging modalities to provide improved pain management, increased level of function, and ultimately an overall better quality of life in the SCI population.

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“…miRNA-221 also directly targets suppressor of cytokine signalling-1 (SOCS-1), which is associated with inflammation [64]. A growing number of studies now show that the immune inflammatory response after SCI plays a crucial role in the injury and recovery process [65][66][67]. This also shows the important role that miRNA-221 plays in the recovery from SCI, especially through inflammation suppression pathways.…”

Section: Mirna-221mentioning

confidence: 99%

Research Progress of MicroRNAs in Spinal Cord Injury

Deng¹,

Chen²

2023

J. Integr. Neurosci.

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Spinal cord injury is a serious and devastating condition. Recently, research into microRNAs (miRNAs) has become increasingly exhaustive and it has been determined that they are closely related to the pathophysiological processes of spinal cord injury. They participate in the regulation of the inflammatory response of spinal cord injury, the death of neuronal cells, and the repair of neural functions, which are related to the recovery of spinal cord injury. This review focuses on the relationship between miRNA and spinal cord injury, lists miRNA-324-5p, miRNA-221 and miRNA-124, which are helpful for the repair of spinal cord injury, and finally summarizes the current research progress of miRNA-based therapies, so as to provide a foundational reference for clinical and scientific researchers.

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Exploring the vagus nerve and the inflammatory reflex for therapeutic benefit in chronic spinal cord injury

Cited by 4 publications

References 90 publications

Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression

Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression

Narrative review of current neuromodulation modalities for spinal cord injury

Research Progress of MicroRNAs in Spinal Cord Injury

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