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Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin
In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV (ITC) injection. Then, we evaluated the efficacy of gabapentin (GBP), an anticonvulsant that binds the voltage-gated Ca2+ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus result...
Source: Neuroscience Bulletin - November 5, 2014 Category: Neuroscience Source Type: research

Gabapentinoid Insensitivity after Repeated Administration is Associated with Down-Regulation of the α 2 δ-1 Subunit in Rats with Central Post-Stroke Pain Hypersensitivity
Abstract The α2δ-1 subunit of the voltage-gated Ca2+ channel (VGCC) is a molecular target of gabapentin (GBP), which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the α2δ-1 subunit to the presynaptic membrane, resulting in decreased neurotransmitter release. We previously showed that GBP has an anti-allodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated administration in a rat model of central post-stroke pain (CPSP) hypersensitivity induced by intra-thalamic h...
Source: Neuroscience Bulletin - January 19, 2016 Category: Neuroscience Source Type: research

Emerging Role of PD-1 in the Central Nervous System and Brain Diseases
AbstractProgrammed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer ’s disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. PD-1 signaling suppresses the CNS immune responsevia resident microglia and infiltrating peripheral immune cells. Notably, PD-1 is also widely express...
Source: Neuroscience Bulletin - April 20, 2021 Category: Neuroscience Source Type: research

Role of the Voltage-Gated Proton Channel Hv1 in Nervous Systems
We describe the recently discovered functions of Hv1 in various neurological diseases, including brain or spinal cord injury, ischemic stroke, demyelinating diseases, and pain. We also summarize the current advances in the discovery and application of Hv1-targeted small molecules in neurological diseases. Finally, we discuss the current limitations of our understanding of Hv1 and suggest future research directions.
Source: Neuroscience Bulletin - April 8, 2023 Category: Neuroscience Source Type: research