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Purpose: Spinal cord stimulation (SCS) is pivotal in treating chronic intractable pain. To elucidate the mechanism of action among conventional and current novel types of SCSs, a stable and reliable electrophysiology model in the consensus animals to mimic human SCS treatment is essential. We have recently developed a new in vivo implantable pulsed-ultrahigh-frequency (pUHF) SCS platform for conducting behavioral and electrophysiological studies in rats. However, some technical details were not fully understood. This study comprehensively analyzed methodology and technical challenges and pitfalls encountered during the development and implementation of this model.
Materials And Methods: Employing a newly developed pUHF-SCS (±3 V, 2 Hz pulses with 500-kHz biphasic radiofrequency sinewaves), we assessed analgesic effect and changes of evoked local field potentials (eLFPs) in the bilateral primary somatosensory and anterior cingulate cortices in the rats with or without spared nerve injury (SNI) using the platform. The placement of stimulating needle electrodes in the hind paw was examined and optimized for functionality.
Results: SNI enhanced the C component of eLFPs in bilateral cortexes elicited by stimulating the contralateral but not the ipsilateral lateral aspect of the hind paw. Repeated pUHF-SCS significantly reversed SNI-induced paw hypersensitivity and reduced C-component enhancement. An impedance test can determine an optimal SCS electrode function: an SCS discharge threshold of 100-400 μA for cortical activation or a motor threshold of 150-600 μA for the hind limbs. Impedance increased due to growth of fibrotic tissue but stabilized after post-implantation day 12.
Conclusion: We presented a reliable electrophysiological platform for SCS application in rat neuropathic pain model and demonstrated potent analgesic effects of pUHF-SCS. All device implantations or pUHF-SCS per se did not cause evident spinal cord damage. This safe and stable platform provides an in vivo rat model for SCS investigation of mechanisms of action and device innovation.
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http://dx.doi.org/10.2147/JPR.S489420 | DOI Listing |
Eur Spine J
September 2025
Consultant Neurosurgeon, Centre for Functional Neurosurgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Stem Cell Rev Rep
September 2025
Stem Cells and Metabolism Research Program (STEMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
Mutations in Delta Like Non-Canonical Notch Ligand 1 (DLK1), a paternally expressed imprinted gene, underlie central precocious puberty (CPP), yet the mechanism remains unclear. To test the hypothesis that DLK1 plays a role in gonadotropin releasing hormone (GnRH) neuron ontogeny, 75 base pairs were deleted in both alleles of DLK1 exon 3 with CRISPR-Cas9 in human pluripotent stem cells (hPSCs). This line, exhibiting More than 80% loss of DLK1 protein, was differentiated into GnRH neurons by dual SMAD inhibition (dSMADi), FGF8 treatment and Notch inhibition, as previously described, however, it did not exhibit accelerated GNRH1 expression.
View Article and Find Full Text PDFPain
August 2025
Centre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
The thermal grill, in which innocuous warm and cool stimuli are interlaced, can produce a paradoxical burning pain sensation-the thermal grill illusion (TGI). Although the mechanisms underlying TGI remain unclear, prominent theories point to spinal dorsal horn integration of innocuous thermal inputs to elicit pain. It remains unknown whether the TGI activates peripheral nociceptors, or solely thermosensitive afferents that are integrated within the spinal cord to give rise to a painful experience.
View Article and Find Full Text PDFNeurol Res
September 2025
Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Objectives: This study aimed to investigate the effects of repeated exposure to sevoflurane as an anesthetic agent during various developmental stages, namely neonatal, preadolescent, and adult, on behavioral, synaptic, and neuronal plasticity in male and female Wistar rats.
Methods: Rats were exposed to sevoflurane during three developmental stages: neonatal (PN7), pre-adolescence (PN28), and adulthood (PN90). Behavioral performance was evaluated with the Morris Water Maze.
Neurol Res
September 2025
Henan Provincial People's Hospital, Department of Surgery of Spine and Spinal Cord, People's Hospital of Zhengzhou University, Zhengzhou, China.
Background: Immunotherapy holds significant yet underexplored potential for low-grade glioma (LGG) treatment. We therefore interrogated the role of Fanconi Anemia Complementation Group C (FANCC) as a novel immune checkpoint regulator given its spatial correlation with tumor microenvironments and clinical associations with immunosuppressive markers.
Objectives: FANCC is implicated in various tumor progressions; its role in LGG remains unexplored.