Molecular interaction in the mouse PAG between NMDA and opioid receptors in morphine induced acute thermal nociception

Autor: George B. Stefano, Wei Zhu, Monica Norcini, Massimo Guarna, Nicoletta Galeotti, E. Vivoli, Carla Ghelardini, Enrica Bianchi
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Popis: Previous evidence demonstrates that low dose morphine systemic administration induces acute thermal hyperalgesia in normal mice through microOR stimulation of the inositol signaling pathway. We investigated the site of action of morphine and the mechanism of action of microOR activation by morphine to NMDA receptor as it relates to acute thermal hyperalgesia. Our experiments show that acute thermal hyperalgesia is blocked in periaqueductal gray with the microOR antagonist CTOP, the NMDA antagonist MK801 and the protein kinase C inhibitor chelerythrine. Therefore, a site of action of systemically administered morphine low dose on acute thermal hyperalgesic response appears to be located at the periaqueductal gray. At this supraspinal site, microOR stimulation by systemically morphine low dose administration leads to an increased phosphorylation of specific subunit of NMDA receptor. Our experiments show that the phosphorylation of subunit 1 of NMDA receptor parallels the acute thermal hyperalgesia suggesting a role for this subunit in morphine-induced hyperalgesia. Protein kinase C appears to be the key element that links microOR activation by morphine administration to mice with the recruitment of the NMDA/glutamatergic system involved in the thermal hyperalgesic response.
Databáze: OpenAIRE