Control of neuropathic pain by lateral parabrachial nucleus

AbstractThe lateral parabrachial nucleus (LPBN) is known to relay noxious information to the amygdala for processing affective responses. However, it is unclear whether the LPBN actively processes neuropathic pain characterized by persistent hyperalgesia with aversive emotional responses. Here we report that neuropathic pain-like hypersensitivity induced by common peroneal nerve (CPN) ligation increases nociceptive stimulation-induced responses in glutamatergic LPBN neurons. Optogenetic activation of GABAergic LPBN neurons does not affect basal nociception, but alleviates neuropathic pain-like behavior. Optogenetic activation of glutamatergic or inhibition of GABAergic LPBN neurons induces neuropathic pain-like behavior in naïve mice. Inhibition of glutamatergic LPBN neurons alleviates both basal nociception and neuropathic pain-like hypersensitivity. Repetitive pharmacogenetic activation of glutamatergic or GABAergic LPBN neurons respectively mimics or prevents the development of CPN ligation-induced neuropathic pain-like hypersensitivity. These findings indicate that a delicate balance between excitatory and inhibitory LPBN neuronal activity governs the development and maintenance of neuropathic pain.

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GLP-1 Receptor Stimulation of the Lateral Parabrachial Nucleus Reduces Food Intake: Neuroanatomical, Electrophysiological, and Behavioral Evidence

Endocrinology ◽

10.1210/en.2014-1248 ◽

2014 ◽

Vol 155 (11) ◽

pp. 4356-4367 ◽

Cited By ~ 46

Author(s):

Jennifer E. Richard ◽

Imre Farkas ◽

Fredrik Anesten ◽

Rozita H. Anderberg ◽

Suzanne L. Dickson ◽

...

Keyword(s):

Feeding Behavior ◽

Fluorescent Protein ◽

Yellow Fluorescent Protein ◽

Parabrachial Nucleus ◽

Lateral Parabrachial Nucleus ◽

Electrophysiological Studies ◽

Glucagon Like Peptide 1 ◽

Behavioral Evidence ◽

Stimulation Of

Abstract The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role in the normal maintenance of feeding behavior, because their loss leads to starvation. Viscerosensory stimuli result in neuronal activation of the PBN. However, the origin and neurochemical identity of the excitatory neuronal input to the PBN remain largely unexplored. Here, we hypothesize that hindbrain glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN, activation of which may lead to a reduction in feeding behavior. Our data, obtained from mice expressing the yellow fluorescent protein in GLP-1-producing neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of chow and palatable food and decreased body weight in rats. It also activated lPBN neurons, reflected by an increase in the number of c-Fos-positive cells in this region. Further support for an excitatory role of GLP-1 in the PBN is provided by electrophysiological studies showing a remarkable increase in firing of lPBN neurons after Exendin-4 application. We show that within the PBN, GLP-1R activation increased gene expression of 2 energy balance regulating peptides, calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application resulted in anorexia. Collectively, our molecular, anatomical, electrophysiological, pharmacological, and behavioral data provide evidence for a functional role of the GLP-1R for feeding control in the PBN.

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Rapid stimulation of sodium intake combining aldosterone into the 4th ventricle and the blockade of the lateral parabrachial nucleus

Neuroscience ◽

10.1016/j.neuroscience.2017.01.005 ◽

2017 ◽

Vol 346 ◽

pp. 94-101 ◽

Cited By ~ 1

Author(s):

S. Gasparini ◽

M.R. Melo ◽

G.F. Leite ◽

P.A. Nascimento ◽

G.M.F. Andrade-Franzé ◽

...

Keyword(s):

Sodium Intake ◽

Parabrachial Nucleus ◽

Lateral Parabrachial Nucleus ◽

Rapid Stimulation ◽

4Th Ventricle ◽

Stimulation Of

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Activation of P2X‐purinergic receptors in the lateral parabrachial nucleus increases renal sympathetic nerve discharge and mean arterial pressure in anesthetized rats (686.13)

The FASEB Journal ◽

10.1096/fasebj.28.1_supplement.686.13 ◽

2014 ◽

Vol 28 (S1) ◽

Author(s):

Miguel Menezes ◽

Michele Favero ◽

Kenta Yamamoto ◽

Jose Menani ◽

Patricia Paula ◽

...

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Sympathetic Nerve ◽

Purinergic Receptors ◽

Parabrachial Nucleus ◽

Renal Sympathetic Nerve ◽

Anesthetized Rats ◽

Lateral Parabrachial Nucleus ◽

Renal Sympathetic ◽

Nerve Discharge

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Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response

10.1101/602466 ◽

2019 ◽

Cited By ~ 1

Author(s):

Michael C. Chiang ◽

Eileen K. Nguyen ◽

Andrew E. Papale ◽

Sarah E. Ross

Keyword(s):

Ventromedial Hypothalamus ◽

Parabrachial Nucleus ◽

Projection Neurons ◽

Pain Response ◽

Neural Pathways ◽

Bed Nucleus ◽

Lateral Parabrachial Nucleus ◽

Efferent Projections ◽

Efferent Neurons ◽

Nociceptive Input

ABSTRACTThe lateral parabrachial nucleus (lPBN) is a major target of spinal projection neurons conveying nociceptive input into supraspinal structures. However, the functional role of distinct lPBN efferents for diverse nocifensive responses have remained largely uncharacterized. Here, we show that two populations of efferent neurons from different regions of the lPBN collateralize to distinct targets. Activation of efferent projections to the ventromedial hypothalamus (VMH) or lateral periaqueductal gray (lPAG) drive escape behaviors, whereas the activation of lPBN efferents to the bed nucleus stria terminalis (BNST) or central amygdala (CEA) generates an aversive memory. Finally, we provide evidence that dynorphin expressing neurons span cytoarchitecturally distinct domains of the lPBN to coordinate these distinct aspects of the nocifensive response.HIGHLIGHTSSpatially segregated neurons in the lPBN collateralize to distinct targets.Distinct output pathways give rise to separate aspects of the pain response.Dynorphin neurons within the lPBN convey noxious information across subdivisions.eTOC BLURBChiang et al. reveal that neurons in spatially segregated regions of the lateral parabrachial nucleus collateralize to distinct targets, and that activation of distinct efferents gives rise to separate components of the nocifensive response.

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Lateral parabrachial nucleus and opioid mechanisms of the central nucleus of the amygdala in the control of sodium intake

Behavioural Brain Research ◽

10.1016/j.bbr.2016.08.035 ◽

2017 ◽

Vol 316 ◽

pp. 11-17 ◽

Cited By ~ 10

Author(s):

Gláucia M.F. Andrade-Franzé ◽

Silvia Gasparini ◽

Laurival A. De Luca ◽

Patrícia M. De Paula ◽

Débora S.A. Colombari ◽

...

Keyword(s):

Sodium Intake ◽

Central Nucleus ◽

Parabrachial Nucleus ◽

Lateral Parabrachial Nucleus ◽

Opioid Mechanisms

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The lateral parabrachial nucleus controls hypertonic, not isotonic, NaCl intake

Appetite ◽

10.1016/j.appet.2008.04.072 ◽

2008 ◽

Vol 51 (2) ◽

pp. 362

Author(s):

L.A. De Luca ◽

R.B. David ◽

A. Godino ◽

L.M. Vivas ◽

J. Antunes-Odrigues ◽

...

Keyword(s):

Parabrachial Nucleus ◽

Lateral Parabrachial Nucleus

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Enhancement of meal-associated hypertonic NaCl intake by moxonidine into the lateral parabrachial nucleus

Behavioural Brain Research ◽

10.1016/j.bbr.2007.06.003 ◽

2007 ◽

Vol 183 (2) ◽

pp. 156-160 ◽

Cited By ~ 9

Author(s):

C ANDRADE ◽

L DELUCAJR ◽

D COLOMBARI ◽

J MENANI

Keyword(s):

Parabrachial Nucleus ◽

Lateral Parabrachial Nucleus

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Adrenomedullin acts in the lateral parabrachial nucleus to increase arterial blood pressure through mechanisms mediated by glutamate and nitric oxide

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00172.2008 ◽

2008 ◽

Vol 295 (1) ◽

pp. R38-R44 ◽

Cited By ~ 1

Author(s):

Adrian Geambasu ◽

Teresa L. Krukoff

Keyword(s):

Nitric Oxide ◽

Calcium Channel ◽

Male Rats ◽

Parabrachial Nucleus ◽

Dependent Manner ◽

Pressor Effect ◽

Arterial Blood ◽

Lateral Parabrachial Nucleus ◽

Nos Inhibitors

Adrenomedullin (ADM) acts in a site-specific manner within autonomic centers of the brain to modulate mean arterial pressure (MAP). To determine the role of ADM in the pontine autonomic center, the lateral parabrachial nucleus (LPBN), we used urethane-anesthetized adult Sprague-Dawley male rats to test the hypothesis that ADM increases MAP at this site through glutamate- and nitric oxide (NO)-dependent mechanisms. ADM microinjected into the LPBN increased MAP in a dose-dependent manner. The pressor effect of ADM (0.01 pmol) had a peak value of 11.9 ± 1.9 mmHg at 2 min and lasted for 7 min. We demonstrated that ADM's effect is receptor mediated by blocking the effect with the ADM receptor antagonist, ADM22-52. We showed that glutamate mediates ADM's pressor response, as this response was blocked using coinjections of ADM with dizolcipine hydrogen maleate or 6-cyano-7-nitroquinoxaline-2,3-dione, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptor antagonists, respectively. We tested the roles of NO with coinjections of ADM with either N5-(1-iminoethyl)-l-ornithine or 7-nitroindazole monosodium salt, nonspecific and neuronal NO synthase (NOS) inhibitors, respectively; both inhibitors blocked ADM's pressor effect. Finally, we studied the role of calcium influx in ADM's pressor effect, as intracellular calcium is important in both glutamate and NO neurotransmission. ADM's effect was blocked when nifedipine, an L-type calcium channel blocker, was coinjected with ADM into the LPBN. This study is the first to show that ADM acts in the LPBN to increase MAP through mechanisms dependent on activation of ionotropic glutamate receptors, neuronal and endothelial NOS-mediated NO synthesis, and L-type calcium channel activation.

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