Intraperiaqueductal gray glycine and D-serine exert dual effects on rostral ventromedial medulla ON- and OFF-cell activity and thermoceptive threshold in the rat.
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.
Department of Experimental Medicine, Second University of Naples, Naples, Italy.
Enza
E
Palazzo
Francesca
F
Guida
Annalucia
A
Migliozzi
Luisa
L
Gatta
Ida
I
Marabese
Livio
L
Luongo
Claudia
C
Rossi
Vito
V
de Novellis
Enrique
E
Fernández-Sánchez
Marie
M
Soukupova
Francisco
F
Zafra
Sabatino
S
Maione
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology*; D008845:Microinjections / Q000379:methods; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012694:Serine / Q000494:pharmacology*; D013331:Strychnine / Q000494:pharmacology; D013623:Tail
D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D012694:Serine; D007736:Kynurenic Acid; D013331:Strychnine; D005998:Glycine