Periaqueductal Gray Metabotropic Glutamate Receptor Subtype 7 and 8 Mediate Opposite Effects on Amino Acid Release, Rostral Ventromedial Medulla Cell Activities, and Thermal Nociception

2007 ◽  
Vol 98 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Ida Marabese ◽  
Francesca Rossi ◽  
Enza Palazzo ◽  
Vito de Novellis ◽  
Katarzyna Starowicz ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Gaba Release ◽  
Periaqueductal Gray ◽  
Rostral Ventromedial Medulla ◽  
Tail Flick ◽  
Receptor Subtype ◽  
Thermal Nociception ◽  
Metabotropic Glutamate ◽  
Tail Flick Latency ◽  
Ventromedial Medulla

The current study has investigated the involvement of periaqueductal gray (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-dicarboxyphenylglycine [( S)-3,4-DCPG (2 and 4 nmol/rat)] or N,N I-dibenzhydrylethane-1,2-diamin dihydrochloride (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 (RS)-α-methylserine-o-phosphate (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 behavior 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.

Dorsal striatum metabotropic glutamate receptor 8 affects nocifensive responses and rostral ventromedial medulla cell activity in neuropathic pain conditions

2014 ◽  
Vol 111 (11) ◽  
pp. 2196-2209 ◽  
Author(s):  
Francesca Rossi ◽  
Ida Marabese ◽  
Maria De Chiaro ◽  
Serena Boccella ◽  
Livio Luongo ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Cell Activity ◽  
Dorsal Striatum ◽  
Rostral Ventromedial Medulla ◽  
Tail Flick ◽  
Metabotropic Glutamate ◽  
Withdrawal Threshold ◽  
Ventromedial Medulla ◽  
Stimulation Of

The present study investigated the role of metabotropic glutamate receptor subtype 8 (mGluR8) in the dorsal striatum (DS) in modulating thermonociception and rostral ventromedial medulla (RVM) ON and OFF cell activities in conditions of neuropathic pain induced by spared nerve injury (SNI) of the sciatic nerve in rats. The role of DS mGluR8 on mechanical allodynia was also investigated. Intra-DS ( S)-3,4-dicarboxyphenylglycine [( S)-3,4-DCPG], a selective mGluR8 agonist, did not modify the activity of the ON and OFF cells in sham-operated rats. In SNI rats, which showed a reduction of the mechanical withdrawal threshold, intra-DS microinjection of ( S)-3,4-DCPG inhibited the ongoing and tail flick-evoked activity of the ON cells while increasing the activity of the OFF cells. AZ12216052, a selective mGluR8 positive allosteric modulator (PAM), behaved like ( S)-3,4-DCPG in increasing tail flick latency and OFF cell activity and decreasing ON cell activity in SNI rats only but was less potent. VU0155041, a selective mGluR4 PAM, was ineffective in changing thermal nociception and ON and OFF cell activity in both sham-operated and SNI rats. ( S)-3,4-DCPG did not change mechanical withdrawal threshold in sham-operated rats but increased it in SNI rats. Furthermore, a decreased level of mGluR8 gene and immunoreactivity, expressed on GABAergic terminals, associated with a protein increase was found in the DS of SNI rats. These results suggest that stimulation of mGluR8 inhibits thermoceptive responses and mechanical allodynia. These effects were associated with inhibition of ON cells and stimulation of OFF cells within RVM.

The inhibiting role of periaqueductal gray metabotropic glutamate receptor subtype 8 in a rat model of central neuropathic pain

2020 ◽  
Vol 42 (6) ◽  
pp. 515-521 ◽  
Author(s):  
Marjan Hosseini ◽  
Mohsen Parviz ◽  
Alireza P. Shabanzadeh ◽  
Elham Zamani ◽  
Parvaneh Mohseni-Moghaddam ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Glutamate Receptor ◽  
Rat Model ◽  
Metabotropic Glutamate Receptor ◽  
Periaqueductal Gray ◽  
Receptor Subtype ◽  
Central Neuropathic Pain ◽  
Metabotropic Glutamate

Intraperiaqueductal Gray Glycine and d-Serine Exert Dual Effects on Rostral Ventromedial Medulla on- and off-Cell Activity and Thermoceptive Threshold in the Rat

2009 ◽  
Vol 102 (6) ◽  
pp. 3169-3179 ◽  
Author(s):  
Enza Palazzo ◽  
Francesca Guida ◽  
Annalucia Migliozzi ◽  
Luisa Gatta ◽  
Ida Marabese ◽  
...  
Keyword(s):  
Glycine Receptor ◽  
Cell Activity ◽  
Rostral Ventromedial Medulla ◽  
Tail Flick ◽  
Glycine Site ◽  
Aspartate Receptor ◽  
Tail Flick Latency ◽  
Ventromedial Medulla ◽  
Cell Firing

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.

Circuitry Underlying Antiopioid Actions of Cholecystokinin Within the Rostral Ventromedial Medulla

2001 ◽  
Vol 85 (1) ◽  
pp. 280-286 ◽  
Author(s):  
M. M. Heinricher ◽  
S. McGaraughty ◽  
V. Tortorici
Keyword(s):  
Rostral Ventromedial Medulla ◽  
Tail Flick ◽  
Opioid Analgesia ◽  
Orphanin Fq ◽  
Tail Flick Latency ◽  
Cell Class ◽  
Cell Recording ◽  
Ventromedial Medulla ◽  
Cell Firing ◽  
Opioid Antinociception

It is now well established that the analgesic actions of opioids can be modified by “anti-analgesic” or “antiopioid” peptides, among them cholecystokinin (CCK). Although the focus of much recent work concerned with CCK-opioid interactions has been at the level of the spinal cord, CCK also acts within the brain to modify opioid analgesia. The aim of the present study was to characterize the actions of CCK in a brain region in which the circuitry mediating the analgesic actions of opioids is relatively well understood, the rostral ventromedial medulla (RVM). Single-cell recording was combined with local infusion of CCK in the RVM and systemic administration of morphine in lightly anesthetized rats. The tail-flick reflex was used as a behavioral index of nociceptive responsiveness. Two classes of RVM neurons with distinct responses to opioids have been identified. off cells are activated, indirectly, by morphine and μ-opioid agonists, and there is strong evidence that this activation is crucial to opioid antinociception. on cells, thought to facilitate nociception, are directly inhibited by opioids. Cells of a third class,neutral cells, do not respond to opioids, and whether they have any role in nociceptive modulation is unknown. CCK microinjected into the RVM by itself had no effect on tail flick latency or the firing of any cell class but significantly attenuated opioid activation of off cells and inhibition of the tail flick. Opioid suppression of on-cell firing was not significantly altered by CCK. Thus CCK acting within the RVM attenuates the analgesic effect of systemically administered morphine by preventing activation of the putative pain inhibiting output neurons of the RVM, the offcells. CCK thus differs from another antiopioid peptide, orphanin FQ/nociceptin, which interferes with opioid analgesia by potently suppressing all off-cell firing.

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