The role of trigeminal nucleus caudalis orexin 1 receptor in orofacial pain-induced anxiety in rat

Bahaaddini, Mehri; Khatamsaz, Saeed; Esmaeili‐Mahani, Saeed; Abbasnejad, Mehdi; Raoof, Maryam

doi:10.1097/wnr.0000000000000660

Cited by 18 publications

(9 citation statements)

References 24 publications

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“…Intracerebroventricular injection of SB-334867 decreases seizures and anxiety in pentylenetetrazol-kindled rats [97]. Systemic SB-334867 administration has no effect on anxietylike behavior in the open field, whereas microinjection of SB-334867 into the trigeminal nucleus caudalis reduces orofacial pain-induced anxiety-like behavior in rats [98,99]. SB-334867 treatment also attenuates FG-7142induced anxiety-like behavior, increases heart rate, and increases neuronal activation in anxiety-and stress-related brain regions, such as the CeA and BNST [100].…”

Section: Mood Disordersmentioning

confidence: 99%

Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders

et al. 2019

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Orexins comprise two neuropeptides produced by orexin neurons in the lateral hypothalamus and are released by extensive projections of these neurons throughout the central nervous system. Orexins bind and activate their associated G protein-coupled orexin type 1 receptors (OX1Rs) and OX2Rs and act on numerous physiological processes, such as sleep-wake regulation, feeding, reward, emotion, and motivation. Research on the development of orexin receptor antagonists has dramatically increased with the approval of suvorexant for the treatment of primary insomnia. In the present review, we discuss recent findings on the involvement of the orexin system in the pathophysiology of psychiatric disorders, including sleep disorders, depression, anxiety, and drug addiction. We discuss the actions of orexin receptor antagonists, including selective OX1R antagonists (SORA1s), selective OX2R antagonists (SORA2s), and dual OX1/2R antagonists (DORAs), in the treatment of these disorders based on both preclinical and clinical evidence. SORA2s and DORAs have more pronounced efficacy in the treatment of sleep disorders, whereas SORA1s may be promising for the treatment of anxiety and drug addiction. We also discuss potential challenges and opportunities for the application of orexin receptor antagonists to clinical interventions.

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Section: Mood Disordersmentioning

confidence: 99%

Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders

et al. 2019

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“…The open field consists of a 60 cm square of dark gray Formica floor surrounded by 50 cm high walls. During the test, each animal was placed in the center of the apparatus and allowed to freely explore for 5 min, as described previously 79 , 80 . After the end of the test, the open field was cleaned with 5% ethanol and subsequently dried with a dry cloth.…”

Section: Methodsmentioning

confidence: 99%

The critical role of amygdala subnuclei in nociceptive and depressive-like behaviors in peripheral neuropathy

Seno

Assis

Gouveia

et al. 2018

Sci Rep

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The amygdala is an important component of the limbic system that participates in the control of the pain response and modulates the affective-motivational aspect of pain. Neuropathic pain is a serious public health problem and has a strong affective-motivational component that makes it difficult to treat. The central (CeA), basolateral (BLA) and lateral (LA) nuclei of the amygdala are involved in the processing and regulation of chronic pain. However, the roles of these nuclei in the maintenance of neuropathic pain, anxiety and depression remain unclear. Thus, the main objective of this study was to investigate the role of amygdala subnuclei in the modulation of neuropathic pain, including the affective-motivational axis, in an experimental model of peripheral neuropathy. The specific goals were as follows: (1) To evaluate the nociceptive responses and the patterns of activation of the CeA, BLA and LA in neuropathic rats; and (2) To evaluate the effect of inactivating the amygdala nuclei on the nociceptive response, anxiety and depressive behaviors, motor activity, and plasma stress hormones in animals with neuropathic pain. Thus, mechanical hyperalgesia and allodynia, and the pattern of c-Fos staining in the amygdala subnuclei were evaluated in rats with chronic constriction of the sciatic nerve, as well as sham-operated and naïve rats. Once the amygdala subnuclei involved in neuropathic pain response were defined, those subnuclei were pharmacological inactivated. The effect of muscimol inactivation on the nociceptive response (hyperalgesia and allodynia), anxiety (elevated plus-maze), depressive-like behavior (forced swim test), motor activity (open field), and plasma stress hormone levels (corticosterone and adrenocorticotropic hormone) were evaluated in sham-operated and neuropathic animals. The results showed that the anterior and posterior portions of the BLA and the central portion of the CeA are involved in controlling neuropathic pain. The inactivation of these nuclei reversed hyperalgesia, allodynia and depressive-like behavior in animals with peripheral neuropathy. Taken together, our findings improve our understanding of the neurocircuitry involved in persistent pain and the roles of specific amygdala subnuclei in the modulation of neuropathic pain, including the neurocircuitry that processes the affective-motivational component of pain.

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“…Examples of behavior tests for animals (e.g. Wistar rats) are open-field-based or maze-based tests (Bahaaddini et al, 2016;Chrousos and Gold, 1992), and these tests are applicable to numerous species, including invertebrates such as planarians and C. elegans (Hagstrom et al, 2016;Qin and Wheeler, 2006). While these tests are easily performed and are normally the starting point for functional studies (Chu et al, 2016), behavioral studies are based on observations, meaning that data misinterpretation or choice of test to monitor changes can produce misleading data.…”

Section: Altering Neuropeptide Contentmentioning

confidence: 99%

New techniques, applications and perspectives in neuropeptide research

DeLaney

Buchberger

Atkinson

et al. 2018

Journal of Experimental Biology

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Neuropeptides are one of the most diverse classes of signaling molecules and have attracted great interest over the years owing to their roles in regulation of a wide range of physiological processes. However, there are unique challenges associated with neuropeptide studies stemming from the highly variable molecular sizes of the peptides, low concentrations, high degree of structural diversity and large number of isoforms. As a result, much effort has been focused on developing new techniques for studying neuropeptides, as well as novel applications directed towards learning more about these endogenous peptides. The areas of importance for neuropeptide studies include structure, localization within tissues, interaction with their receptors, including ion channels, and physiological function. Here, we discuss these aspects and the associated techniques, focusing on technologies that have demonstrated potential in advancing the field in recent years. Most identification and structural information has been gained by mass spectrometry, either alone or with confirmations from other techniques, such as nuclear magnetic resonance spectroscopy and other spectroscopic tools. While mass spectrometry and bioinformatic tools have proven to be the most powerful for large-scale analyses, they still rely heavily on complementary methods for confirmation. Localization within tissues, for example, can be probed by mass spectrometry imaging, immunohistochemistry and radioimmunoassays. Functional information has been gained primarily from behavioral studies coupled with tissue-specific assays, electrophysiology, mass spectrometry and optogenetic tools. Concerning the receptors for neuropeptides, the discovery of ion channels that are directly gated by neuropeptides opens up the possibility of developing a new generation of tools for neuroscience, which could be used to monitor neuropeptide release or to specifically change the membrane potential of neurons. It is expected that future neuropeptide research will involve the integration of complementary bioanalytical technologies and functional assays.

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The role of trigeminal nucleus caudalis orexin 1 receptor in orofacial pain-induced anxiety in rat

Cited by 18 publications

References 24 publications

Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders

Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders

The critical role of amygdala subnuclei in nociceptive and depressive-like behaviors in peripheral neuropathy

New techniques, applications and perspectives in neuropeptide research

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