Opposing Roles of Corticotropin-Releasing Factor and Neuropeptide Y within the Dorsolateral Bed Nucleus of the Stria Terminalis in the Negative Affective Component of Pain in Rats

Ide, Soichiro; Hara, Taiki; Ohno, Atsushi; Tamano, Ryuta; Koseki, Kana; Naka, Tomonori; Maruyama, Chikashi; Kaneda, Katsuyuki; Yoshioka, Mitsuhiro; Minami, Masabumi

doi:10.1523/jneurosci.4278-12.2013

Cited by 59 publications

(69 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This test, in which mice learn to avoid a chamber where they experienced pain induced by formalin injection to the hind paw, has been used extensively to investigate the affective component of pain in rodents (3,5,6,8). To explore the role of prostaglandins, we first interfered with the cyclooxygenases COX1 and COX2 (also known as PTGS1 and PTGS2), enzymes responsible for prostaglandin synthesis.…”

Section: Resultsmentioning

confidence: 99%

Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain

Singh¹,

Zajdel²,

Mirrasekhian³

et al. 2017

Journal of Clinical Investigation

View full text Add to dashboard Cite

Pain is fundamentally unpleasant and induces a negative affective state. The affective component of pain is mediated by circuits that are distinct from those mediating the sensory-discriminative component. Here, we have investigated the role of prostaglandins in the affective dimension of pain using a rodent pain assay based on conditioned place aversion to formalin injection, an inflammatory noxious stimulus. We found that place aversion induced by inflammatory pain depends on prostaglandin E-2 that is synthesized by cyclooxygenase 2 in neural cells. Further, mice lacking the prostaglandin E-2 receptor EP3 selectively on serotonergic cells or selectively in the area of the dorsal raphe nucleus failed to form an aversion to formalininduced pain, as did mice lacking the serotonin transporter. Chemogenetic manipulations revealed that EP3 receptor activation elicited conditioned place aversion to pain via inhibition of serotonergic neurons. In contrast to their role in inflammatory pain aversion, EP3 receptors on serotonergic cells were dispensable for acute nociceptive behaviors and for aversion induced by thermal pain or a kappa opioid receptor agonist. Collectively, our findings show that prostaglandin-mediated modulation of serotonergic transmission controls the affective component of inflammatory pain.

Funding Agencies|European Research Council; Swedish Medical Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain Foundation; County Council of Ostergotland; National Institute of Neurological Disorders and Stroke (NINDS)

show abstract

Section: Resultsmentioning

confidence: 99%

Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain

Singh¹,

Zajdel²,

Mirrasekhian³

et al. 2017

Journal of Clinical Investigation

View full text Add to dashboard Cite

show abstract

“…Whereas PKC-δ + neurons in the CeA L represent -fear off‖ neurons (Haubensak et al, 2010), perhaps Type II PKC-δ + cells represent -anxiety off‖ neurons in the BNST ( Figure 1D). In addition to inhibition via local GABAergic connections, CRF action and CRF neurons themselves are opposed by NPY (Ide et al, 2013;Kash and Winder, 2006;Pleil et al, 2015). In fact, NPY in the BNST has been shown to block CRF-induced-place aversion (Ide et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to inhibition via local GABAergic connections, CRF action and CRF neurons themselves are opposed by NPY (Ide et al, 2013;Kash and Winder, 2006;Pleil et al, 2015). In fact, NPY in the BNST has been shown to block CRF-induced-place aversion (Ide et al, 2013). More studies on peptides and the local circuitry involved in the regulation of CRF neuron activity are needed to better understand how the BNST modulates anxiety.…”

Section: Introductionmentioning

confidence: 99%

Stress Modulation of Opposing Circuits in the Bed Nucleus of the Stria Terminalis

Daniel

Rainnie

2015

Neuropsychopharmacol

175

191

View full text Add to dashboard Cite

The anterior bed nucleus of the stria terminalis (BNST) has been recognized as a critical structure in regulating trait anxiety, contextual fear memory, and appetitive behavior, and is known to be sensitive to stress manipulations. As one of the most complex structures in the central nervous system, the intrinsic circuitry of the BNST is largely unknown; however, recent technological developments have allowed researchers to begin to untangle the internal connections of the nucleus. This research has revealed the possibility of two opposing circuits, one anxiolytic and one anxiogenic, within the BNST, the relative strength of which determines the behavioral outcome. The balance of these pathways is critical in maintaining a normal physiological and behavioral state; however, stress and drugs of abuse can differentially affect the opposing circuitry within the nucleus to shift the balance to a pathological state. In this review, we will examine how stress interacts with the neuromodulators, corticotropin-releasing factor, norepinephrine, dopamine, and serotonin to affect the circuitry of the BNST as well as how synaptic plasticity in the BNST is modulated by stress, resulting in long-lasting changes in the circuit and behavioral state.

show abstract

“…receptor antagonists, BIBP-3226 and L-152,804, respectively (Ide et al, 2013). Although many studies have found that NPY typically reduces synaptic transmission, it is interesting to note that NPY can also enhance inhibitory transmission.…”

mentioning

confidence: 99%

The role of Neuropeptide Y in fear conditioning and extinction

et al. 2016

View full text Add to dashboard Cite

While anxiety disorders are the brain disorders with the highest prevalence and constitute a major burden for society, a considerable number of affected people are still treated insufficiently. Thus, in an attempt to identify potential new anxiolytic drug targets, neuropeptides have gained considerable attention in recent years. Compared to classical neurotransmitters they often have a regionally restricted distribution and may bind to several distinct receptor subtypes. Neuropeptide Y (NPY) is a highly conserved neuropeptide that is specifically concentrated in limbic brain areas and signals via at least 5 different G-protein-coupled receptors. It is involved in a variety of physiological processes including the modulation of emotional-affective behaviors. An anxiolytic and stress-reducing property of NPY is supported by many preclinical studies. Whether NPY may also interact with processing of learned fear and fear extinction is comparatively unknown. However, this has considerable relevance since pathological, inappropriate and generalized fear expression and impaired fear extinction are hallmarks of human post-traumatic stress disorder and a major reason for its treatment-resistance. Recent evidence from different laboratories emphasizes a fear-reducing role of NPY, predominantly mediated by exogenous NPY acting on Y1 receptors. Since a reduction of fear expression was also observed in Y1 receptor knockout mice, other Y receptors may be equally important. By acting on Y2 receptors, NPY promotes fear extinction and generates a long-term suppression of fear, two important preconditions that could support cognitive behavioral therapies in human patients. A similar effect has been demonstrated for the closely related pancreatic polypeptide (PP) when acting on Y4 receptors. Preliminary evidence suggests that NPY modulates fear in particular by activation of Y1 and Y2 receptors in the basolateral and central amygdala, respectively. In the basolateral amygdala, NPY signaling activates inhibitory G protein-coupled inwardly-rectifying potassium channels or suppresses hyperpolarization-induced I(h) currents in a Y1 receptor-dependent fashion, favoring a general suppression of neuronal activity. A more complex situation has been described for the central extended amygdala, where NPY reduces the frequency of inhibitory and excitatory postsynaptic currents. In particular the inhibition of long-range central amygdala output neurons may result in a Y2 receptor-dependent suppression of fear. The role of NPY in processes of learned fear and fear extinction is, however, only beginning to emerge, and multiple questions regarding the relevance of endogenous NPY and different receptor subtypes remain elusive. Y2 receptors may be of particular interest for future studies, since they are the most prominent Y receptor subtype in the human brain and thus among the most promising therapeutic drug targets when translating preclinical evidence to potential new therapies for human anxiety disorders.

show abstract

Opposing Roles of Corticotropin-Releasing Factor and Neuropeptide Y within the Dorsolateral Bed Nucleus of the Stria Terminalis in the Negative Affective Component of Pain in Rats

Cited by 59 publications

References 43 publications

Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain

Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain

Stress Modulation of Opposing Circuits in the Bed Nucleus of the Stria Terminalis

The role of Neuropeptide Y in fear conditioning and extinction

Contact Info

Product

Resources

About