Metabotropic glutamate antagonists alone and in combination with morphine

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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.