Objective It has been revealed that peripheral persistent nociception results in spatial and temporal synaptic plasticity in rat hippocampal formation (HF), however, the underlying mechanisms are still unknown.In the present report, we present a line of evidence implicating opposing roles of metabotropic glutamate receptor (mGluR) subtype 1 and 5 in mediation of pain-related spatial and temporal synaptic plasticity in the HF.Methods Inhibitors targeting mGluR1 and mGluR5 were used, respectively.Spatial and temporal components of entorhinal-hippocampal synaptic connections and efficacy of rats were recorded by using a newly developed 64-channels (8 × 8) multi-electrode array technique (Med64 system).Results (1) Pharmacological inhibition ofmGluR5 activation, at the plateau phase of the long-term potentiation (LTP), effectively decreased pain-enhanced hippocampal long-term potentiation (LTP) maintenance, while similar blockade of mGluR1 resulted in an even higher level of potentiation.(2) The mGluR subtype-related difference was also detected when analyzing effects of these two drugs on the spatial amplification of pain, with no clear involvement of mGluR5 and a negative modulation exerted by mGluR1.Conclusion These findings suggest differential and even contradictory roles of mGluR1 and mGluR5 in pain-associated spatial and temporal plasticity of synaptic responses.More importantly, this maybe the first demonstration for a subtype-linked functional separation/opposition regarding roles of group Ⅰ mGluRs in higher levels of abnormal pain processing in the HF.