Brain research
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N-methyl-d-aspartate (NMDA) receptor and protein kinase C (PKC) play important roles in the induction and maintenance of central sensitization during pain states. It has been shown that spinal NMDA receptor-dependent activation of PKCgamma facilitates nociception during neuropathic and inflammatory pain, but its involvement in bone cancer pain has not previously been established. The aim of this study was to examine the potential role of the spinal NMDA receptor/PKCgamma signaling pathway in the development of bone cancer pain. ⋯ At day 14, intrathecal administration of 5 microg of NR2B subunit-specific NMDA receptor antagonist ifenprodil attenuated the up-regulation of PKCgamma mRNA in the spinal cord as well as bone cancer-evoked thermal hyperalgesia and mechanical allodynia. Furthermore, intrathecal injection of 10 microg of PKC inhibitor H-7 attenuated cancer-evoked thermal hyperalgesia and mechanical allodynia at day 14. These results suggest that the NMDA receptor/PKCgamma signaling pathway may participate in the development of bone cancer pain, and ifenprodil may be a useful alternative or adjunct therapy for bone cancer pain.
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Working memory capacity (WMC) represents proficiency in allocating limited attentional resources. Previous studies on individual differences in WMC have shown that high WMC subjects have a superior ability to inhibit goal-irrelevant information, while low WMC subjects have difficulty in inhibiting such information. The present study aimed to reveal the neural structure that differentiates the inhibitory ability between subjects with high and low WMC. ⋯ As expected, the bilateral IFG showed greater activation in the stronger distraction condition; however, the magnitude did not differ between WMC groups, suggesting that the IFG functions to inhibit intensive distractors, but appears to be independent of the individual differences in inhibitory ability. On the other hand, the activation of the bilateral FFG in the low WMC group was stronger than in the high WMC group, while the activation of the left MFG was stronger in the high WMC group than in the low WMC group. These results indicate that the superior inhibitory ability in high WMC subjects may depend on the efficient top-down modulation from the left MFG to the posterior perceptual areas.
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Glutamate is the main excitatory neurotransmitter in the brain, while gamma-aminobutyric acid (GABA) is a primary inhibitory neuromodulator. Both amino acids act through ionotropic and metabotropic receptors that are widely distributed in the central nervous system. There are at least eight subtypes of metabotropic glutamate receptors (mGlu), which have been divided into three groups (mGlu I, II, and III). ⋯ The protein levels of GAD65 was lowered in mGlu7-/- animals only, while GAD67 and GABA(B) receptor number were decreased in both mGlu7+/- and mGlu7-/- mice when measured in the whole hippocampus. In contrast, reelin was shown to be increased both in mGlu7-/+ and mGlu7-/- mice. The results suggest that mGlu7 receptor is involved in the regulation of GABAergic system activity at the level of GABA synthesised enzymes, specific proteins expressed by GABAergic neurons and metabotropic receptor for GABA.