Dr. Hayashida's Research Projects
Mechanisms of gabapentin analgesia in the locus coeruleus (LC).
1. Gabapentin (GBP) inhibits GABA release to increase the influence/release of glutamate. Glutamate induces Ca2+ influx through AMPA receptors to result in activation of LC neurons. GABA induces hyperpolarization of cell membrane via Cl- influx through GABA-A receptors and inhibits cell excitation. GABA also inhibits glutamate release via GABA-B receptors activation.
2. GBP induces spinal noradrenaline release as a consequence of activation of LC neurons.
Roles of glial glutamate transporters on the activation of locus coeruleus neurons.
In the central nervous system, glial glutamate transporters (GLT-1 and GLAST) regulate extracellular glutamate, which stimulates various neurons via AMPA/NMDA receptors. We are now examining the functions of GLT-1 and GLAST in the locus coeruleus in normal and neuropathic pain conditions.