The present study examined the effects of the
mGluR1 antagonist
JNJ16259685 (JNJ) and the mGluR5 antagonist 2-methyl-6-phenylethynylpyridine (MPEP) alone and in combination with
morphine in two
acute pain models (hotplate, warm water tail-withdrawal), and a persistent, inflammatory
pain model (
capsaicin). In the hotplate and warm water tail-withdrawal procedures, JNJ and MPEP were ineffective when administered alone. In both procedures, JNJ potentiated
morphine antinociception. In the hotplate procedure, MPEP potentiated
morphine antinociception at the highest dose examined, whereas in the warm water tail-withdrawal procedure MPEP attenuated
morphine antinociception at a moderate dose and potentiated
morphine antinociception at a high dose. For both JNJ and MPEP, the magnitude of this
morphine potentiation was considerably greater in the hotplate procedure. In the
capsaicin procedure, the highest dose of MPEP produced intermediate levels of antihyperalgesia and also attenuated the effects of a dose of
morphine that produced intermediate levels of antihyperalgesia. In contrast, JNJ had no effect when administered alone in the
capsaicin procedure and did not alter
morphine-induced antihyperalgesia. The present findings suggest that the effects produced by
mGluR1 and mGluR5 antagonists alone and in combination with
morphine can be differentiated in models of both acute and persistent
pain.