Work-related musculoskeletal disorders associated with intense repetitive tasks are highly prevalent. Painful symptoms associated with such disorders can be attributed to neuropathy. In this study, we characterized the neuronal discharge from the median nerve in rats trained to perform an operant repetitive task. After 3-weeks of the task, rats developed pain behaviors and a decline in grip strength. Ongoing activity developed in 17.7% of slowly conducting neurons at 3-weeks, similar to neuritis. At 12-weeks, an irregular high frequency neuronal discharge was prevalent in >88.4% of slow and fast conducting neurons. At this time point, 8.3% of slow and 21.2% of fast conducting neurons developed a bursting discharge, which, combined with a reduction in fast-conducting neurons with receptive fields (38.4%), is consistent with marked neuropathology. Taken together, we have shown that an operant repetitive task leads to an active and progressive neuropathy that is characterized by marked neuropathology following 12-weeks task that mainly affects fast conducting neurons. Such aberrant neuronal activity may underlie painful symptoms in patients with work-related musculoskeletal disorders. PERSPECTIVE: Aberrant neuronal activity, similar to that reported in this study, may contribute to upper limb pain and dysfunction in patients with work-related musculoskeletal disorders. In addition, profiles of instantaneous frequencies may provide an effective way of stratifying patients with painful neuropathies.
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http://dx.doi.org/10.1016/j.jpain.2021.12.004 | DOI Listing |
Acta Neuropathol Commun
January 2025
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185, Rome, Italy.
The generation of retinal models from human induced pluripotent stem cells holds significant potential for advancing our understanding of retinal development, neurodegeneration, and the in vitro modeling of neurodegenerative disorders. The retina, as an accessible part of the central nervous system, offers a unique window into these processes, making it invaluable for both study and early diagnosis. This study investigates the impact of the Frontotemporal Dementia-linked IVS 10 + 16 MAPT mutation on retinal development and function using 2D and 3D retinal models derived from human induced pluripotent stem cells.
View Article and Find Full Text PDFSci Rep
January 2025
Centre for Psychedelic Research, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; which (b) facilitate positive therapeutic outcomes and are associated with the entropy of EEG signals. Healthy individuals (N = 11) were administered 1 mg and 25 mg psilocybin 4-weeks apart.
View Article and Find Full Text PDFCommun Biol
January 2025
School of Psychology and Sussex Neuroscience, University of Sussex, Brighton, UK.
Reduced cerebral blood flow occurs early in the development of Alzheimer's disease (AD), but the factors producing this reduction are unknown. Here, we ask whether genetic and lifestyle risk factors for AD-the ε4 allele of the Apolipoprotein (APOE) gene, and physical activity-can together produce this reduction in cerebral blood flow which leads eventually to AD. Using in vivo two-photon microscopy and haemodynamic measures, we record neurovascular function from the visual cortex of physically active or sedentary mice expressing APOE3 and APOE4 in place of murine APOE.
View Article and Find Full Text PDFJ Neurosci
January 2025
Department of Neuroscience, Brown University, Providence RI, USA.
Voltage-gated potassium conductances [Formula: see text] play a critical role not only in normal neural function, but also in many neurological disorders and related therapeutic interventions. In particular, in an important animal model of epileptic seizures, 4-aminopyridine (4-AP) administration is thought to induce seizures by reducing [Formula: see text] in cortex and other brain areas. Interestingly, 4-AP has also been useful in the treatment of neurological disorders such as multiple sclerosis (MS) and spinal cord injury, where it is thought to improve action potential propagation in axonal fibers.
View Article and Find Full Text PDFJ Neurosci
January 2025
Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada
Action potentials (spikes) are regenerated at each node of Ranvier during saltatory transmission along a myelinated axon. The high density of voltage-gated sodium channels required by nodes to reliably transmit spikes increases the risk of ectopic spike generation in the axon. Here we show that ectopic spiking is avoided because K1 channels prevent nodes from responding to slow depolarization; instead, axons respond selectively to rapid depolarization because K1 channels implement a high-pass filter.
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