Metabotropic glutamate receptor activation contributes to nociceptive reflex activity in the rat spinal cord in vitro

• Published in: Neuroscience Vol. 74; no. 1; pp. 13 - 20
• Main Authors: BOXALL, S. J, THOMPSON, S. W. N, DRAY, A, DICKENSON, A. H, URBAN, L
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01.09.1996
• Subjects: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; N-Methylaspartate - pharmacology; Nociceptors - drug effects; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate - drug effects; Reflex - physiology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Spinal Cord - drug effects; Spinal Cord - physiology; Vertebrates: nervous system and sense organs; Nociception; Reflex; Vertebrata; Spinal cord; Mammalia; Rat; Metabotropic receptor; Electrical stimulus; Rodentia; Central nervous system; Electrophysiology; Glutamate receptor
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/0306-4522(96)00101-7

The contribution of metabotropic glutamate receptor activation to the spinal segmental reflex response evoked at high-intensity electrical stimulation suggesting a role in nociception, has been examined in an in vitro preparation of neonatal rat spinal cord. Segmental reflex responses were recorded as a ventral root depolarization evoked following drug perfusion to the spinal cord or by electrical activation of high-threshold nociceptive afferent fibres. Superfusion of the selective metabotropic glutamate receptor agonist, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], to the spinal cord produced a dose-dependent, reversible ventral root depolarization (EC50 = 58 +/- 7 microM; n = 4), which was antagonized by the selective metabotropic glutamate receptor antagonist, (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; IC50 = 243 +/- 61 microM; n = 4). MCPG, over the same concentration range (10 microM-5.0 mM) did not affect N-methyl-D-aspartate-induced ventral root depolarizations. In contrast, the specific N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) reduced N-methyl-D-aspartate-evoked ventral root depolarization but did not affect the depolarization evoked by (1S,3R)-ACPD, thus indicating the specificity of the antagonists for these aggregate responses. MCPG significantly reduced the prolonged phase of the single shock C-fibre-evoked ventral root depolarization (IC50 = 2.9 +/- 0.2 mM; n = 3-5). Low frequency high intensity stimulation of the dorsal root evoked a wind-up response, the amplitude of which was attenuated by both D-AP5 and MCPG in a dose-dependent manner. The ventral root depolarization evoked by capsaicin application (1.0 microM, 30 s) was blocked by both MCPG (IC50 = 809 +/- 35 microM; n = 4) and D-AP5 (IC50 = 143 +/- 43 microM; n = 4). These data suggest that both D-AP5 and MCPG reduced C-fibre-induced ventral root responses. In addition to N-methyl-D-aspartate receptor, metabotropic glutamate receptor activation appears to be involved in the generation of the segmental spinal reflex evoked by high-intensity stimulation in the neonatal rat spinal cord in vitro.