PMID- 19776366 OWN - NLM STAT- MEDLINE DCOM- 20100222 LR - 20131121 IS - 1522-1598 (Electronic) IS - 0022-3077 (Linking) VI - 102 IP - 6 DP - 2009 Dec TI - Intraperiaqueductal gray glycine and D-serine exert dual effects on rostral ventromedial medulla ON- and OFF-cell activity and thermoceptive threshold in the rat. PG - 3169-79 LID - 10.1152/jn.00124.2009 [doi] AB - We have studied the involvement of the N-methyl-D-aspartate receptor (NMDAR) glycine site and the strychnine-sensitive glycine receptor (GlyR) in the ventrolateral periaqueductal gray (VL-PAG) on nociceptive behavior (tail flick) and pain-related changes on neuronal activity in the rostral ventromedial medulla (RVM). Glycine or D-serine increased the tail-flick latency, reduced OFF-cell pause, and delayed its onset and increased the time between the onset of the OFF-cell pause and the tail withdrawal. Conversely, they decreased the ongoing activity of the ON cell, the tail-flick-induced ON-cell firing, whereas they delayed the onset of increased tail-flick-induced ON-cell firing. Also, glycine or D-serine reduced the interval between the onset of the increased ON-cell firing and tail withdrawal. Whereas 7-Cl-kynurenic acid (7-Cl-KYN) prevented such effects, strychnine did not do so. A higher dose of 7-Cl-KYN or strychnine was per se able to reduce or increase tail-flick latency and increase or reduce ON-cell activities, respectively. A higher dose of glycine was hyperalgesic in the presence of 7-Cl-KYN, whereas such an effect was prevented by strychnine. These data suggest 1) a dual role of glycine in producing hyperalgesia or analgesia by stimulating the GlyR or the NMDARs within the VL-PAG, respectively; 2) consistently that RVM ON and OFF cells display opposite firing patterns to the stimulation of the VL-PAG NMDAR glycine site and GlyR activation; and 3) a tonic role of these receptors within the VL-PAG-RVM antinociceptive descending pathway. FAU - Palazzo, Enza AU - Palazzo E AD - Department of Experimental Medicine, Second University of Naples, Naples, Italy. FAU - Guida, Francesca AU - Guida F FAU - Migliozzi, Annalucia AU - Migliozzi A FAU - Gatta, Luisa AU - Gatta L FAU - Marabese, Ida AU - Marabese I FAU - Luongo, Livio AU - Luongo L FAU - Rossi, Claudia AU - Rossi C FAU - de Novellis, Vito AU - de Novellis V FAU - Fernandez-Sanchez, Enrique AU - Fernandez-Sanchez E FAU - Soukupova, Marie AU - Soukupova M FAU - Zafra, Francisco AU - Zafra F FAU - Maione, Sabatino AU - Maione S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090923 PL - United States TA - J Neurophysiol JT - Journal of neurophysiology JID - 0375404 RN - 0 (Drug Combinations) RN - 0 (Excitatory Amino Acid Antagonists) RN - 452VLY9402 (Serine) RN - H030S2S85J (Kynurenic Acid) RN - H9Y79VD43J (Strychnine) RN - TE7660XO1C (Glycine) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Dose-Response Relationship, Drug MH - Drug Combinations MH - Excitatory Amino Acid Antagonists/pharmacology MH - Glycine/*pharmacology MH - Kynurenic Acid/pharmacology MH - Male MH - Medulla Oblongata/*cytology MH - Microinjections/methods MH - Neural Pathways/physiology MH - Neurons/cytology/*physiology MH - Pain Measurement/methods MH - Pain Threshold/drug effects MH - Periaqueductal Gray/*drug effects MH - Rats MH - Rats, Wistar MH - Reaction Time/drug effects MH - Serine/*pharmacology MH - Strychnine/pharmacology MH - Tail EDAT- 2009/09/25 06:00 MHDA- 2010/02/23 06:00 CRDT- 2009/09/25 06:00 PHST- 2009/09/25 06:00 [entrez] PHST- 2009/09/25 06:00 [pubmed] PHST- 2010/02/23 06:00 [medline] AID - 00124.2009 [pii] AID - 10.1152/jn.00124.2009 [doi] PST - ppublish SO - J Neurophysiol. 2009 Dec;102(6):3169-79. doi: 10.1152/jn.00124.2009. Epub 2009 Sep 23.