Analgesia produced by microinjection ofl-glutamate into the rostral ventromedial bulbar nuclei of the rat and its inhibition by intrathecal α-adrenergic blocking agents

Satoh, Masamichi; Oku, Ryoya; Akaike, Akinori

doi:10.1016/0006-8993(83)90646-7

Cited by 97 publications

(34 citation statements)

References 16 publications

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“…Thus, like ON and OFF cells, our data along with these earlier studies show that Neutral cells receive direct input from the PAG and project to the spinal cord. Although electrophysiological analysis reveals no relationship between changes in nociception and activity in Neutral cells [11], pharmacological studies show that blocking serotonin receptors in the spinal cord attenuates antinociception mediated by the RVM [31, 43]. Thus, serotonin does not appear to contribute to antinociception directly but may modulate nociception depending on the situation.…”

Section: Discussionmentioning

confidence: 99%

Periaqueductal gray neurons project to spinally projecting GABAergic neurons in the rostral ventromedial medulla

Morgan

Whittier

Hegarty

et al. 2008

Pain

126

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The analgesic effects of morphine are mediated, in part, by periaqueductal gray (PAG) neurons that project to the rostral ventromedial medulla (RVM). Although much of the neural circuitry within the RVM has been described, the relationship between RVM neurons and PAG input and spinal output is not known. The objective of this study was to determine whether GABAergic output neurons from the PAG target RVM reticulospinal neurons. Immunocytochemistry and confocal microscopy revealed that PAG neurons project extensively to RVM neurons projecting to the spinal cord, and two-thirds of these reticulospinal neurons appear to be GABAergic (contain GAD67 immunoreactivity). The majority (71%) of PAG fibers that contact RVM reticulospinal GAD67-immunoreactive neurons also contained GAD67 immunoreactivity. Thus, there is an inhibitory projection from PAG to inhibitory RVM reticulospinal neurons. However, there also were PAG projections to the RVM that did not contain GAD67 immunoreactivity. Additional experiments were conducted to determine whether the heterogeneity in this projection can be explained by the electrophysiological character of the RVM target neurons. PAG projections to electrophysiologically defined and juxtacellularly filled ON, OFF, and Neutral cells in the RVM were examined. Similar to the pattern reported above, both GAD67- and non-GAD67-immunoreactive PAG neurons project to RVM ON, OFF, and Neutral cells in the RVM. These inputs include a GAD67-immunoreactive projection to a GAD67-immunoreactive ON cell and non-GAD67 projections to GAD67-immunoreactive OFF cells. This pattern is consistent with PAG neurons producing antinociception by direct excitation of RVM OFF cells and inhibition of ON cells.

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Section: Discussionmentioning

confidence: 99%

Periaqueductal gray neurons project to spinally projecting GABAergic neurons in the rostral ventromedial medulla

Morgan

Whittier

Hegarty

et al. 2008

Pain

126

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“…The function of these neurons in the modulation of nociception has been well established (Casey, 1971;Gebhart et al, 1983;Gray and Dostrovsky, 1983;Le Blanc and Gatipon, 1974). Neurons in this region are activated by peripheral noxious stimulation (Casey, 1971;LeBlanc and Gatipon, 1974), whereas stimulation of this area has been reported to alter nociceptive transmission (Basbaum and Fields, 1984;Clark and Proudfit, 1991;Fields and Basbaum, 1978;Satoh et al, 1983;Zhou and Gebhart, 1990). In addition, neurons in this medial portion of the rostral ventral medulla have been shown to respond to chemoreceptor input (Miura et al, 1996), project to medullary respiratory neurons, and innervate phrenic motor neurons, suggesting that these neurons are also involved in the regulation of respiration (Dobbins and Feldman, 1994;Ellenberger and Feldman, 1990;Ellenberger et al, 1992;Hadziefendic and Haxhiu, 1999;Holtman and Speck, 1994;Smith et al, 1989).…”

mentioning

confidence: 96%

Medullary and spinal cord projections from cardiovascular responsive sites in the rostral ventromedial medulla

Babic

Ciriello

2004

J of Comparative Neurology

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The rostral ventromedial medulla (RVMM) is a sympathoexcitatory area. However, little is known about its efferent projections. In this study, biotinylated dextran amine (BDA) or Phaseolus vulgaris leucoagglutinin (PHA-L) were used to investigate the medullary and spinal cord projections from pressor sites in RVMM. Initially, RVMM was systematically explored in urethane-anesthetized rats using microinjection of L-glutamate for sites that elicited increases in arterial pressure. A pressor area was identified that included the rostral magnocellular reticular and rostral lateral paragigantocellular reticular nuclei. In the second series of experiments, BDA or PHA-L was iontophoretically injected into RVMM pressor sites. Anterograde labeling was observed throughout the brainstem and spinal cord, bilaterally, but with an ipsilateral predominance. Dense labeling was observed within the nucleus of the solitary tract (NTS); the greatest density of labeling was observed in the caudal dorsolateral, medial, and ventrolateral subnuclei. Additionally, light to moderately dense labeling was found within the nucleus substantia gelatinosus and commissural nucleus. In the nucleus ambiguus/ventrolateral medullary (Amb/VLM) region, the density of labeling was greatest in caudal regions. Within Amb, most of the labeling was localized to its external formation. Anterograde labeling was also found throughout the spinal cord. In the thoracolumbar segments, dense axonal labeling was observed within the dorsolateral funiculus. These labeled axons innervated the intermediolateral nucleus and the central autonomic area. Taken together, these data suggest that RVMM neurons elicit increases in sympathetic activity by likely providing a direct excitatory input to spinal sympathetic preganglionic neurons, and by a direct inhibitory input to medullary cardioinhibitory and depressor areas.

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“…Excitatory amino acid (EAA) receptors in the RVM have been implicated in antinociceptive processes given the actions of glutamate and NMDA [42,75]. EAA antagonists in the RVM significantly reduce antinociception elicited by either electrical or opioid stimulation of the vlPAG [2, 91].…”

Section: Opioid Agonists In the Vlpag And Excitatory Amino Acid Antagmentioning

confidence: 99%

Supraspinal Circuitry Mediating Opioid Antinociception: Antagonist and Synergy Studies in Multiple Sites

Bodnar¹

2000

J Biomed Sci

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Supraspinal opioid antinociception is mediated by sensitive brain sites capable of supporting this response following microinjection of opioid agonists. These sites include the ventrolateral periaqueductal gray (vIPAG), the rostral ventromedial medulla (RVM), the locus coeruleus and the amygdala. Each of these sites comprise an interconnected anatomical and physiologically relevant system mediating antinociceptive responses through regional interactions. Such interactions have been identified using two pharmacological approaches: (1) the ability of selective antagonists delivered to one site to block antinociception elicited by opioid agonists in a second site, and (2) the presence of synergistic antinociceptive interactions following simultaneous administration of subthreshold doses of opioid agonists into pairs of sites. Thus, the RVM has essential serotonergic, opioid, cholinergic and NMDA synapses that are necessary for the full expression of morphine antinociception elicited from the vIPAG, and the vIPAG has essential opioid synapses that are necessary for the full expression of opioid antinociception elicited from the amygdala. Further, the vIPAG, RVM, locus coeruleus and amygdala interact with each other in synergistically supporting opioid antinociception.

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Analgesia produced by microinjection ofl-glutamate into the rostral ventromedial bulbar nuclei of the rat and its inhibition by intrathecal α-adrenergic blocking agents

Cited by 97 publications

References 16 publications

Periaqueductal gray neurons project to spinally projecting GABAergic neurons in the rostral ventromedial medulla

Periaqueductal gray neurons project to spinally projecting GABAergic neurons in the rostral ventromedial medulla

Medullary and spinal cord projections from cardiovascular responsive sites in the rostral ventromedial medulla

Supraspinal Circuitry Mediating Opioid Antinociception: Antagonist and Synergy Studies in Multiple Sites

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