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- W2253256002 abstract "The α2δ-1 subunit of the voltage-gated Ca(2+) 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 hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the α2δ-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the α2δ-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of α2δ-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the α2δ-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor α2δ-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use." @default.
- W2253256002 created "2016-06-24" @default.
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- W2253256002 date "2016-01-19" @default.
- W2253256002 modified "2023-10-17" @default.
- W2253256002 title "Gabapentinoid Insensitivity after Repeated Administration is Associated with Down-Regulation of the α2δ-1 Subunit in Rats with Central Post-Stroke Pain Hypersensitivity" @default.
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- W2253256002 doi "https://doi.org/10.1007/s12264-015-0008-3" @default.
- W2253256002 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5563753" @default.
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