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.

Abstract

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.