Submitted on March 29, 2007
Accepted on May 8, 2007
Periaqueductal grey metabotropic glutamate receptor 7 and 8 mediate opposite effects on amino acid release, rostral ventromedial medulla cell activities and thermal nociception
Ida Marabese1, Francesca Rossi1, Enza Palazzo1, Vito de Novellis1, Katarzyna Starowicz2, Luigia Cristino3, Daniela Vita4, Luisa Gatta4, Francesca Guida1, Vincenzo Di Marzo5, Francesco Rossi4, and Sabatino Maione4*
1 Department of Experimental Medicine, Second University of Naples, Naples, Italy
2 Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy
3 Endocannabinoid Research Group, Institute of Cybernetics "E. Caianiello", Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy
4 Department of Experimental Medicine, Second University of Naples, Italy
5 Endocannabinoid Research Group, Institute of Biomolecular Chemistry, CNR, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy
* To whom correspondence should be addressed. E-mail: sabatino.maione{at}unina2.it.
The current study has investigated the involvement of periaqueductal grey (PAG) metabotropic glutamate subtype 7 and 8 receptors (mGluR7 and mGluR8) in modulating rostral ventromedial medulla (RVM) ongoing and tail flick-related ON and OFF cell activities. Our study has also investigated the role of PAG mGluR7 on thermoceptive threshold and PAG glutamate and GABA release. Intra-ventrolateral PAG (S)-3,4-DCPG (2 and 4 nmol/rat) or AMN082 (1 and 2 nmol/rat), selective mGluR8 and mGluR7 agonists respectively, caused opposite effects on the ongoing RVM ON and OFF cell activities. Tail flick latency was increased or decreased by (S)-3,4-DCPG or AMN082 (2 nmol/rat) respectively. (S)-3,4-DCPG reduced the pause and delayed the onset of the OFF cell pause. Conversely, AMN082 increased the pause and shortened the onset of OFF cell pause. (S)-3,4-DCPG or AMN082 did not change the tail flick-induced onset of ON-cell peak firing. The tail flick latency and its related electrophysiological effects induced by (S)-3,4-DCPG or AMN082 were prevented by MSOP (100 nmol/rat), a group III mGluR antagonist. Intra-ventrolateral PAG perfusion with AMN082 (10 and 25 µM), decreased thermoceptive thresholds and glutamate extracellular levels. A decrease in GABA release was also observed. These results show that stimulation of PAG mGluR8 or mGluR7 could either relieve or worsen pain perception. The opposite effects on pain behaviour correlate with the opposite roles played by mGluR7 and mGluR8 on glutamate and GABA release and the ongoing and tail flick-related activities of the RVM ON and OFF cells.
