Antinociception produced by microinjection ofl-glutamate into the ventromedial medulla of the rat: mediation by spinal GABAA receptors

McGowan, Malcolm K.; Hammond, Donna L.

doi:10.1016/0006-8993(93)90274-q

Cited by 66 publications

(26 citation statements)

References 45 publications

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“…Reichling and Basbaum (1990) have reported that, although GABA-immunoreactive neurons are abundant in the RVM, those sending axons to the spinal dorsal horn are unevenly distributed in the RVM; i.e., only 2% of retrogradely labeled neurons are in the NRM, whereas 6 -15 and 15-30% of retrogradely labeled neurons are in the pararaphe nuclei (NGC and NGC␣, respectively). Furthermore, it has been suggested that chemical activation of bulbospinal GABAergic neurons in the NGC␣ is more likely to induce antinociceptive effects than those in the NRM (McGowan and Hammond, 1993). In the present study, because we aimed mainly at the raphe nuclei in the RVM, 21 of 23 (Ͼ90%) of the stimulating sites were located in the raphe nuclei (NRM and NRP) and only 2 were in the NGC␣.…”

Section: Discussionmentioning

confidence: 72%

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

et al. 2006

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Stimulation of the rostral ventromedial medulla (RVM) is believed to exert analgesic effects through the activation of the serotonergic system descending to the spinal dorsal horn; however, how nociceptive transmission is modulated by the descending system has not been fully clarified. To investigate the inhibitory mechanisms affected by the RVM, an in vivo patch-clamp technique was used to record IPSCs from the substantia gelatinosa (SG) of the spinal cord evoked by chemical (glutamate injection) and electrical stimulation (ES) of the RVM in adult rats. In the voltage-clamp mode, the RVM glutamate injection and RVM-ES produced an increase in both the frequency and amplitude of IPSCs in SG neurons that was not blocked by glutamate receptor antagonists. Serotonin receptor antagonists were unexpectedly without effect, but a GABA A receptor antagonist, bicuculline, or a glycine receptor antagonist, strychnine, completely suppressed the RVM stimulation-induced increase in IPSCs. The RVM-ES-evoked IPSCs showed fixed latency and no failure at 20 Hz stimuli with a conduction velocity of Ͼ3 m/s (3.1-20.7 m/s), suggesting descending monosynaptic GABAergic and/or glycinergic inputs from the RVM to the SG through myelinated fibers. In the current-clamp mode, action potentials elicited by noxious mechanical stimuli applied to the receptive field of the ipsilateral hindlimb were suppressed by the RVM-ES in more than half of the neurons tested (63%; 10 of 16). These findings suggest that the RVM-mediated antinociceptive effects on noxious inputs to the SG may be exerted preferentially by the direct GABAergic and glycinergic pathways to the SG.

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Section: Discussionmentioning

confidence: 72%

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

et al. 2006

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“…Lamina I1 (particularly LII,), also displayed strong pz/ p3-subunit immunoreactivity; this area contains the arborizations of some nociceptive small afferents (Sugiura et al, 1987) which are labeled here by GSA-IB4 binding. Pharmacological evidence also suggests an involvement of GABAA receptors (for reviews, see Sawynok, 1987;McGowan and Hammond, 1993) and, in particular, benzodiazepine modulation (Goodchild and Serrao, 1987;Clavier et al, 1992) in the control of nociceptive transmission at spinal cord levels. However, this proposal is controversial, because the sedative and myorelaxant properties of enhanced GABAA activation make it difficult to evaluate specific effects on sensory input (see Sosnowski and Yaksh, 1990).…”

Section: Functional Implications Of Gaband Receptor Distribution In Thementioning

confidence: 97%

Distribution of immunoreactivity for the β ₂ and β ₃ subunits of the GABA _A receptor in the mammalian spinal cord

et al. 1996

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The localization of GABAA receptors in cat and rat spinal cord was analyzed using two monoclonal antibodies specific for an epitope shared by the beta 2 and beta 3 subunits of the receptor. beta 2/beta 3-subunit immunoreactivity was the most intense in inner lamina II, lamina III, and lamina X, and it was the least intense in lamina IX. In laminae I-III, generally, the staining had a rather diffuse appearance, but the surfaces of small cell bodies in these laminae were outlined clearly by discrete labeling, as were many cell bodies and dendrites in deeper laminae. Rhizotomy experiments and ultrastructural observations indicated that beta 2/beta 3-subunit immunoreactivity in the dorsal horn was largely localized in intrinsic neuropil elements rather than in the terminals of primary afferent fibers, even though labeling overlapped with the terminal fields of different types of primary afferents and was also detected on the membranes of dorsal root ganglion neurons. With few exceptions (most notably, a highly immunoreactive group of dorsolaterally located cells in the cat lumbar ventral horn), motoneurons expressed low levels of beta 2/beta 3-subunit immunoreactivity. Labeling of neuronal membranes was fairly continuous, but focal accumulations of beta 2/beta 3-subunit immunoreactivity were also detected using immunofluorescence. Focal "hot spots" correlated ultrastructurally with the presence of synaptic junctions. Dual-color immunofluorescence revealed that focal accumulations of beta 2/beta 3-subunit immunoreactivity were frequently apposed by glutamic acid decarboxylase (GAD)-immunoreactive terminals. However, the density of continuous-membrane beta 2/beta 3 immunolabeling and GAD terminal density were not correlated in many individual neurons. The results suggest the existence of "classical" (synaptic) and "nonclassical" (paracrine) actions mediated via spinal cord GABAA receptors. The study also revealed the relative paucity of beta 2/beta 3-subunit immunoreactivity postsynaptic to certain GABAergic terminals, particularly those presynaptic to motoneurons or primary afferent terminals.

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“…This pathway typically includes the PAG and its projection to the RVM, which in turn sends terminals to modulate nociceptive inputs at the level of the spinal dorsal horn (Basbaum and Fields, 1984;Manning, 1998). Activation of this pathway, by glutamate, opioids, or electrical stimulation, results in profound antinociception (Basbaum and Fields, 1984;McGowan and Hammond, 1993). Although the CeA is important for opioid analgesia (Manning and Mayer, 1995b;Manning, 1998), the cellular mechanisms underlying the opioid action in the CeA are little known.…”

mentioning

confidence: 99%

Effect of the μ Opioid on Excitatory and Inhibitory Synaptic Inputs to Periaqueductal Gray-Projecting Neurons in the Amygdala

Finnegan

Chen

Pan

2005

The Journal of Pharmacology and Experimental Therapeutics

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Opioids are potent analgesics, but the sites of their action and cellular mechanisms are not fully understood. The central nucleus of the amygdala (CeA) is important for opioid analgesia through the projection to the periaquaductal gray (PAG). In this study, we examined the effects of opioid receptor stimulation on inhibitory and excitatory synaptic inputs to PAG-projecting CeA neurons retrogradely labeled with a fluorescent tracer injected into the ventrolateral PAG of rats. Whole-cell voltageclamp recordings were performed on labeled CeA neurons in brain slices. The specific opioid receptor agonist, [D-Ala 2 ,NMe-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO, 1 M), significantly reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs) without altering the amplitude and decay constant of mIPSCs in 47.6% (10 of 21) of cells tested. DAMGO also significantly decreased the peak amplitude of evoked IPSCs in 69% (9 of 13) of cells examined. However, DAMGO did not significantly alter the frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitude of evoked EPSCs in 69% (9 of 13) and 83% (10 of 12) of labeled cells, respectively. The IPSCs were blocked by the GABA A receptor antagonist bicuculline, whereas the EPSCs were largely abolished by the non-N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. The immunoreactivity of opioid receptors was colocalized with synaptophysin, a presynaptic marker, in close appositions to labeled CeA neurons. These results suggest that activation of opioid receptors on presynaptic terminals primarily attenuates GABAergic synaptic inputs to PAG-projecting neurons in the CeA.

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Antinociception produced by microinjection ofl-glutamate into the ventromedial medulla of the rat: mediation by spinal GABAA receptors

Cited by 66 publications

References 45 publications

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

Distribution of immunoreactivity for the β ₂ and β ₃ subunits of the GABA _A receptor in the mammalian spinal cord

Effect of the μ Opioid on Excitatory and Inhibitory Synaptic Inputs to Periaqueductal Gray-Projecting Neurons in the Amygdala

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Antinociception produced by microinjection ofl-glutamate into the ventromedial medulla of the rat: mediation by spinal GABAA receptors

Cited by 66 publications

References 45 publications

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

Distribution of immunoreactivity for the β 2 and β 3 subunits of the GABA A receptor in the mammalian spinal cord

Effect of the μ Opioid on Excitatory and Inhibitory Synaptic Inputs to Periaqueductal Gray-Projecting Neurons in the Amygdala

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Distribution of immunoreactivity for the β ₂ and β ₃ subunits of the GABA _A receptor in the mammalian spinal cord