| Popis: |
Publisher Summary This chapter discusses the role of the N -methyl- D -aspartate (NMDA) receptor in pain transmission. The NMDA receptor antagonist (DL-CPP) is a piperazine derivative that acts competitively at the glutamate recognition site. The NMDA receptor-mediated increase in intracellular calcium initiates a cascade of intracellular events, responsible for the development of neuronal plasticity. While neuropeptides and excitatory amino acids (EAAs) acting at the non-NMDA receptors lower the threshold for neuron activation, the NMDA receptor activation amplifies and prolongs the response to depolarization. A case study, where the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (DL-CPP) was given intrathecally at the lumbar level for the treatment of a severe, intractable, chronic pain state, is summarized: DL-CPP, administered intrathecally in a dose of 200 nmol, completely eliminated the spread of pain sensation from the territory of the injured nerve to the left body half, and it abolished after discharge. Molecular cloning of the genes for the NMDA receptor as well as for other EAA receptors has revealed that the receptors consist of a number of subunits, and the variability in the way these subunits combine, at different anatomical locations, may represent a molecular basis for the functional diversity of the receptors. |
