Glutamate uptake inhibition modulates dorsal horn neurotransmission: a comparison between normal and arthritic rats

This study determined the effects of glutamate uptake inhibition on primary-afferent excitatory postsynaptic potentials (DR-EPSPs) in spinal dorsal horn neurones in vitro from naive rats and rats with localised arthritis. The glutamate uptake inhibitor L-PDC (1 mM) significantly reduced DR-EPSP amplitude and duration with a greater reduction in arthritic than in naive rats. The group II/III selective metabotropic glutamate receptor antagonist CPPG (100 microM) reversed L-PDC-induced DR-EPSP inhibition in naive but not arthritic rats. L-AP4 (30 microM), a group III metabotropic agonist, inhibited DR-EPSPs with no difference between naive and arthritic rats. These data suggest the existence of an autoregulatory feedback mechanism that limits spinal postsynaptic excitation especially during inflammation. The putative contribution of metabotropic glutamate receptors to this phenomenon is discussed.