Metabotropic glutamate subtype 7 and 8 receptors oppositely modulate cardiac nociception in the rat nucleus tractus solitarius

Recent study from our laboratory has indicated that microinjection of glutamate into the nucleus tractus solitarius (NTS) facilitates the cardiac-somatic reflex induced by pericardial capsaicin. Further, N-methyl-d-aspartate (NMDA) receptors and metabotropic glutamate receptors (mGluRs) mediate this function. However, the roles of the individual receptor subtypes or subunits in modulating cardiac nociception are unknown. Among the three groups of mGluRs, group III mGluRs are the primary mGluR subtype expressed in visceral afferent neurons in the NTS. The present study examined the roles of group III mGluRs and their subtype 7 and 8 receptors (mGluR7 and mGluR8) in modulating the cardiac-somatic reflex induced by pericardial capsaicin, which was monitored by recording electromyogram (EMG) activity from the spinotrapezius muscle in anesthetized rats. Intra-NTS microinjection of a group III mGluR agonist, l-(+)-2-Amino-4-phosphonobutyric acid (l-AP4, at 1, 10, and 20 nmol) or a selective mGluR7 agonist, N,N'-diphenylmethyl-1,2-ethanediamine dihydrochloride (AMN082, at 1, 2, and 4 nmol) both decreased the EMG response in a dose-dependent manner. This decrease was inhibited by the group III mGluR antagonist (RS)-α-Methylserine-O-phosphate (MSOP, at 20 nmol). In contrast, intra-NTS microinjection of a selective mGluR8 agonist, (S)-3, 4-dicarboxyphenylglycine (DCPG, at 6 and 8 nmol), significantly increased the EMG response above control levels. This effect was eliminated by intra-NTS MSOP and by vagal deafferentation. These data suggest that group III mGluRs and mGluR7 in the NTS display an inhibitory effect, while mGluR8 displays a facilitatory effect in modulating cardiac nociception, and this facilitatory effect is dependent on vagal afferents.