Abstract:Orexin is a neuropeptide that is primarily synthesized and secreted by the lateral hypothalamus (LH) and includes two substances derived from the same precursor (orexin A [OXA] and orexin B [OXB]). Studies have shown that orexin is not only involved in the regulation of eating, the sleep–wake cycle, and energy metabolism, but also closely associated with various physiological functions, such as cardiovascular control, reproduction, stress, reward, addiction, and the modulation of pain transmission. At present,… Show more
“…In addition, dense projections from Ox neurons in other spinal, diencephalic and cortical regions are involved in regulating diverse behavioral and physiological functions [ 34 ]. Therefore, Ox is not only implicated in the regulation of eating, the sleep-wake cycle, and energy metabolism, but also closely associated with cardiovascular control, reproduction, stress, reward, addiction, cognition and mood, and the modulation of pain transmission [ 37 , 38 ].…”
Section: Place Of Orexin Neurons In Sleep-wake Regulationmentioning
confidence: 99%
“…In addition, because specific sleep parameters, particularly slow-wave sleep intensity, are considered predictive of the magnitude of an antigen-specific immune response [ 21 ], the impact of reactogenic sleep on immunogenicity of COVID-19 vaccines should be studied. Nevertheless, considering the multifunctionality of Ox neurons in the modulation of vital physiological processes, this assumption could also be valid to explain other transient reactogenic symptoms such as general weakness, loss of appetite, headache, myalgia and joint pain after COVID vaccination [ 15 , 37 , 38 ]. Fig.…”
Section: Inflammatory Regulation Of the Arousal A Possible Implicatio...mentioning
confidence: 99%
“…In addition to SARS-CoV-2 or other virus infections, vaccination can also cause autoimmune reactions by mechanisms such as molecular mimicry and bystander activation of T cells [ 89 ]. In this context, a dysfunction of the orexinergic system may trigger sleep disorders and different pathological conditions, including obesity, depression, cognitive disorders, and chronic pain, among others [ 37 , 38 ]. Subsequently, these antecedents should be an alert of special interest to be monitored in pharmacovigilance studies, like others, not a reason why some individuals choose to refuse protective vaccines.…”
Section: Alerting Elements To Consider In Pharmacovigilance Studies I...mentioning
“…In addition, dense projections from Ox neurons in other spinal, diencephalic and cortical regions are involved in regulating diverse behavioral and physiological functions [ 34 ]. Therefore, Ox is not only implicated in the regulation of eating, the sleep-wake cycle, and energy metabolism, but also closely associated with cardiovascular control, reproduction, stress, reward, addiction, cognition and mood, and the modulation of pain transmission [ 37 , 38 ].…”
Section: Place Of Orexin Neurons In Sleep-wake Regulationmentioning
confidence: 99%
“…In addition, because specific sleep parameters, particularly slow-wave sleep intensity, are considered predictive of the magnitude of an antigen-specific immune response [ 21 ], the impact of reactogenic sleep on immunogenicity of COVID-19 vaccines should be studied. Nevertheless, considering the multifunctionality of Ox neurons in the modulation of vital physiological processes, this assumption could also be valid to explain other transient reactogenic symptoms such as general weakness, loss of appetite, headache, myalgia and joint pain after COVID vaccination [ 15 , 37 , 38 ]. Fig.…”
Section: Inflammatory Regulation Of the Arousal A Possible Implicatio...mentioning
confidence: 99%
“…In addition to SARS-CoV-2 or other virus infections, vaccination can also cause autoimmune reactions by mechanisms such as molecular mimicry and bystander activation of T cells [ 89 ]. In this context, a dysfunction of the orexinergic system may trigger sleep disorders and different pathological conditions, including obesity, depression, cognitive disorders, and chronic pain, among others [ 37 , 38 ]. Subsequently, these antecedents should be an alert of special interest to be monitored in pharmacovigilance studies, like others, not a reason why some individuals choose to refuse protective vaccines.…”
Section: Alerting Elements To Consider In Pharmacovigilance Studies I...mentioning
“… 116 Psychiatric conditions' underlying pathophysiology could be elucidated by a better understanding of pain processing in them, particularly due to the psychobiological overlap between these pathways. 116 Pain regulation closely associates with the Orx-S. 117 , 118 Manipulation of orexin neurons influences pain-related behaviors; therefore, activation of the Orx-S has been proposed as a novel approach to analgesic treatment. 28 In addition, suvorexant has shown efficacy in improving sleep time and reducing next-day pain sensitivity, such as in patients with fibromyalgia and comorbid insomnia.…”
Section: Orx-s Dysfunction and Main Symptom Domain Of Essence Within ...mentioning
Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations (ESSENCE) is an umbrella term covering a wide range of neurodevelopmental difficulties and disorders. Thus, ESSENCE includes attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and other neurodevelopmental disorders (NDDs) and difficulties, with a variety of symptoms in cognitive, motor, sensory, social, arousal, regulatory, emotional, and behavioral developmental domains, frequently co-occurring and likely having partly common neurobiological substrates. The ESSENCE concept is a clinical paradigm that promotes organizing NDDs in everyday clinical practice according to their coexistence, symptom dimensions overlapping, and treatment possibilities. Despite increased knowledge regarding NDDs, the neurobiological mechanisms that underlie them and other ESSENCE-related problems, are not well understood. With its wide range of neural circuits and interactions with numerous neurotransmitters, the orexin/hypocretin system (Orx-S) is possibly associated with a variety of neurocognitive, psychobiological, neuroendocrine, and physiological functions and behaviors. Dysfunction of Orx-S has been implicated in various psychiatric and neurological disorders. This article provides an overview of Orx-S dysfunctions' possible involvement in the development, presentation, and maintenance of ESSENCE. We provide a focused review of current research evidence linking orexin neuropeptides with specific clinical NDDs symptoms, mostly in ADHD and ASD, within the Research Domain Criteria (RDoC) framework. We propose that Orx-S dysfunction might have an important role in some of these neurodevelopmental symptom domains, such as arousal, wakefulness, sleep, motor and sensory processing, mood and emotional regulation, fear processing, reward, feeding, attention, executive functions, and sociability. Our perspective is presented from a clinical point of view. Further, more thorough systematic reviews are needed as well as planning of extensive new research into the Orx-S’s role in ESSENCE, especially considering RDoC elements.
“…Neurons containing orexin are localized exclusively in the lateral hypothalamus (LH), and their projections are widely distributed in multiple brain regions such as the limbic system, locus coeruleus, periaqueductal gray matter, reticular formation, and trigeminal caudate nucleus [for review see (Kang et al, 2021)]. Chemical stimulation of LH attenuated the nociceptive responses in several animal pain models such as acute and chronic, as well as orofacial pain [for review see (Razavi and Hosseinzadeh, 2017)].…”
Chemical stimulation of the lateral hypothalamus (LH) induces analgesia by formation neural circuitries with multiple brain regions. The involvement of hippocampal dopaminergic receptors in the LH stimulation-induced antinociception in certain animal models of pain has been documented, however, considering the fact that the neural circuitries involved in the mediation of orofacial pain are not the same as those that mediate the other types of pain, the present study aims to detect the role of dopamine receptors within the dentate gyrus (DG) in the antinociceptive responses induced by LH stimulation in an animal model of orofacial pain. Male Wistar rats (220-250 g) were implanted with two separate cannulae into the LH and DG on the same side. D1- or D2-like dopamine receptor antagonist, SCH23390 or Sulpiride (0.25, 1, and 4 μg) were microinjected into the DG, five minutes prior to intra-LH injection of carbachol (250 nM). The animals were then injected with formalin 1% (50 μl; sc) into the upper lip lateral to the nose and subjected to the orofacial formalin test. Intra-DG administration of SCH23390 or Sulpiride attenuated the antinociceptive responses induced by intra-LH microinjection of carbachol during orofacial formalin test. The findings of the current study suggest that chemical stimulation of the LH modulates the orofacial pain possibly through activation of the DG dopaminergic neurons. Due to the high incidence and prevalence of orofacial pain in the general population, understanding how such neuronal circuitry modulates nociceptive processing will advance the search for novel therapeutics.
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