title: Dorsal striatum metabotropic glutamate receptor 8 affects nocifensive responses and rostral ventromedial medulla cell activity in neuropathic pain conditions.
abstract: 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.
authors.affiliation: Department of Woman, Child and Specialist Surgery, The Second University of Naples, Naples, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, Naples, Italy; and.
authors.forename: Ida
authors.initials: I
authors.lastname: Marabese
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, Naples, Italy; and.
authors.forename: Maria
authors.initials: M
authors.lastname: De Chiaro
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, Naples, Italy; and.
authors.forename: Serena
authors.initials: S
authors.lastname: Boccella
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, Naples, Italy; and.
authors.forename: Livio
authors.initials: L
authors.lastname: Luongo
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, Naples, Italy; and.
authors.forename: Francesca
authors.initials: F
authors.lastname: Guida
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, Naples, Italy; and.
authors.forename: Danilo
authors.initials: D
authors.lastname: De Gregorio
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, Naples, Italy; and.
authors.forename: Catia
authors.initials: C
authors.lastname: Giordano
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, Naples, Italy; and.
authors.forename: Vito
authors.initials: V
authors.lastname: de Novellis
authors.affiliation: Department of Anesthesiology, Surgery and Emergency, The Second University of Naples, Naples, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Palazzo
authors.affiliation: Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, Naples, Italy; and sabatino.maione@unina2.it.
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D003342:Corpus Striatum / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000503:physiopathology*; D009437:Neuralgia / Q000503:physiopathology*; D059225:Nociception; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012018:Reflex; D013697:Thermosensing; D014110:Touch
chemical_list: D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8
keywords: dorsal striatum; mechanical allodynia; metabotropic glutamate receptor subtype 8; rostral ventromedial medulla; spared nerve injury