Induction of long-term potentiation of C fibre-evoked spinal field potentials requires recruitment of group I, but not group II/III metabotropic glutamate receptors.
In superficial layers of the lumbar spinal dorsal horn, N-methyl-D-aspartate-dependent long-term potentiation (LTP) of C fibre-evoked field potentials, a synaptic model of central sensitisation and hyperalgesia, ensues the application of electrical high-frequency, high-intensity conditioning stimulation to the sciatic nerve. In order to investigate the putative involvement of the G protein-coupled metabotropic glutamate receptors (mGluRs) in the induction of this form of LTP, we applied a series of mGluR antagonists exhibiting distinct group-specific activity profiles to the spinal lumbar enlargement, prior to conditioning stimulation. The group I (mGluR1/5) and group II (mGluR2/3) mGluR antagonist (S)-alpha-methyl-4-carboxyphenylglycine or the selective mGluR1/5 antagonist (S)-4-carboxyphenylglycine consistently impaired the development of spinal LTP. However, potentiation occurred in the presence of the inactive enantiomer (R)-alpha-methyl-4-carboxyphenylglycine. LTP proved insensitive to the selective mGluR2/3 antagonists (2S)-alpha-ethylglutamic acid and LY341495, either spinally or intravenously delivered. LTP could also be induced in the presence of the selective group III (mGluR4/mGluR6-mGluR8) mGluR antagonist (RS)-alpha-methylserine-O-phosphate. However, none of the mGluR-active compounds alone noticeably altered the amplitudes of C fibre-evoked field potentials in the absence of conditioning stimulation. These findings suggest that the induction of LTP of C fibre-evoked field potentials in the spinal dorsal horn by high-frequency, high-intensity stimulation of afferent C fibres requires a group-specific mGluR recruitment, activation of mGluR1/5 but not that of mGluR4/6-8 and mGluR2/3 being a requisite step.
Azkue
Jon Jatsu
JJ
School of Medicine and Dentistry, The University of the Basque Country, Sarriena s/n 48940 Leioa, Spain Institute of Physiology and Pathophysiology, Heidelberg University, Im Neuenheimer Feld 326, D-69120 Heidelberg, Germany.
Liu
Xian-Guo
XG
Zimmermann
Manfred
M
Sandkühler
Jürgen
J
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104077:metabotropic glutamate receptor type 1