Abstract
Orexin A and B (also named hypocretin 1 and 2) are 33 and 28 amino acid-containing neuropeptides, respectively, derived from prepro-orexin (prepro-hypocretin) which is localized in the lateral and perifonical areas of the hypothalamus. Two G-protein coupled receptor subtypes, OX1 and OX2, were identified. Orexin-containing fibers and OX receptors are widely distributed in the central nervous system. Orexins have been implicated in the arousal, rewarding, energy homeostasis, autonomic central control and antinociceptive systems. Subtype-selective peptide agonists and antagonists and non-peptide antagonists, but not non-peptide agonists, have been developed. This review summarizes the studies investigating the antinociceptive effects of orexins in various animal models of pain, including trigeminovascular pain, and their cellular mechanisms. Orexins are antinociceptive at both spinal and supraspinal levels. The antinociceptive effect of orexin A is comparable to opioids but orexin B is less or not effective. This effect is opioid-independent and mainly mediated through OX1 receptors. Some animal studies suggest that endogenous orexins may be released during postoperative and inflammatory, but not acute, pain states, or during some stress conditions, which may contribute to stress-induced analgesia. Purinergic P2X and glycine receptors are proposed to be involved in orexin-induced spinal antinociception. The supraspinal sites of actions might involve the posterior hypothalamus, which contributes to the trigeminovascular nociception, and the ventrolateral periaqueductal gray, which mediates descending pain inhibition. Endocannobinoids and nociceptin/orphanin FQ were found to interplay with orexins in nocicpetive processing. Further studies are required to elucidate the receptor subtype-specific mechanism(s) and clinical implications of orexin-induced antinociception.
Keywords: Orexins/Hypocretins, OX1/OX2 receptors, Nociceptin/Orphanin FQ, Pain, Endocannabinoids, Migraine, Cluster headache
Current Pharmaceutical Design
Title: Orexins/Hypocretins: Pain Regulation and Cellular Actions
Volume: 16 Issue: 28
Author(s): Lih-Chu Chiou, Hsin-Jung Lee, Yu-Cheng Ho, Shih-Pin Chen, Yan-Yu Liao, Chia-Hau Ma, Pi-Chuan Fan, Jong-Ling Fuh and Shuu-Jiun Wang
Affiliation:
Keywords: Orexins/Hypocretins, OX1/OX2 receptors, Nociceptin/Orphanin FQ, Pain, Endocannabinoids, Migraine, Cluster headache
Abstract: Orexin A and B (also named hypocretin 1 and 2) are 33 and 28 amino acid-containing neuropeptides, respectively, derived from prepro-orexin (prepro-hypocretin) which is localized in the lateral and perifonical areas of the hypothalamus. Two G-protein coupled receptor subtypes, OX1 and OX2, were identified. Orexin-containing fibers and OX receptors are widely distributed in the central nervous system. Orexins have been implicated in the arousal, rewarding, energy homeostasis, autonomic central control and antinociceptive systems. Subtype-selective peptide agonists and antagonists and non-peptide antagonists, but not non-peptide agonists, have been developed. This review summarizes the studies investigating the antinociceptive effects of orexins in various animal models of pain, including trigeminovascular pain, and their cellular mechanisms. Orexins are antinociceptive at both spinal and supraspinal levels. The antinociceptive effect of orexin A is comparable to opioids but orexin B is less or not effective. This effect is opioid-independent and mainly mediated through OX1 receptors. Some animal studies suggest that endogenous orexins may be released during postoperative and inflammatory, but not acute, pain states, or during some stress conditions, which may contribute to stress-induced analgesia. Purinergic P2X and glycine receptors are proposed to be involved in orexin-induced spinal antinociception. The supraspinal sites of actions might involve the posterior hypothalamus, which contributes to the trigeminovascular nociception, and the ventrolateral periaqueductal gray, which mediates descending pain inhibition. Endocannobinoids and nociceptin/orphanin FQ were found to interplay with orexins in nocicpetive processing. Further studies are required to elucidate the receptor subtype-specific mechanism(s) and clinical implications of orexin-induced antinociception.
Export Options
About this article
Cite this article as:
Chiou Lih-Chu, Lee Hsin-Jung, Ho Yu-Cheng, Chen Shih-Pin, Liao Yan-Yu, Ma Chia-Hau, Fan Pi-Chuan, Fuh Jong-Ling and Wang Shuu-Jiun, Orexins/Hypocretins: Pain Regulation and Cellular Actions, Current Pharmaceutical Design 2010; 16 (28) . https://dx.doi.org/10.2174/138161210793292483
DOI https://dx.doi.org/10.2174/138161210793292483 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Myocardial Infarction Following Atherosclerosis in Murine Models
Current Drug Targets Therapeutic Strategies for Treatment of Inflammation-related Depression
Current Neuropharmacology Inhibition of Aurora A Kinase by Alisertib Induces Autophagy and Cell Cycle Arrest and Increases Chemosensitivity in Human Hepatocellular Carcinoma HepG2 Cells
Current Cancer Drug Targets Genetic Variants in Diseases of the Extrapyramidal System
Current Genomics Proteomic Analysis of Alzheimers Disease Cerebrospinal Fluid from Neuropathologically Diagnosed Subjects
Current Alzheimer Research The Nature of Immunological Reaction in the Peripheral Airways of Cigarette Smokers
Current Respiratory Medicine Reviews Comparative Analysis of In Vitro Rat Liver Metabolism of the Antimalarial Primaquine and a Derived Imidazoquine
Drug Metabolism Letters Current Management of Vascular Tumors in the Neonate
Current Pediatric Reviews Meet Our Editorial Board Member
Current Neuropharmacology Potential Advantages of Using Synchrotron X-ray Based Techniques in Pediatric Research
Current Medicinal Chemistry Diabetic Theory in Anti-Alzheimer’s Drug Research and Development - Part 1: Therapeutic Potential of Antidiabetic Agents
Current Medicinal Chemistry Synthetic and Biological Aspects of Thiadiazoles and their Condensed Derivatives: An Overview
Current Topics in Medicinal Chemistry Neurogenesis as a New Target for the Development of Antidepressant Drugs
Current Pharmaceutical Design Working Memory in ADHD: Prefrontal/Parietal Connections
Current Drug Targets Editorial (Thematic Issue: Health Impact and Management of a Disrupted Circadian Rhythm and Sleep in Critical Illnesses)
Current Pharmaceutical Design NF-κ B and Rheumatic Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Neurodegeneration in Niemann-Pick Type C Disease and Huntingtons Disease: Impact of Defects in Membrane Trafficking
Current Drug Targets Inflammatory Aspects of Depression
Inflammation & Allergy - Drug Targets (Discontinued) Editorial [Hot topic: An Overview on the Design, Development, Characterization and Applications of Novel Nanomedicines for Brain Targeting (Guest Editor: Eliana B. Souto)]
Current Nanoscience Ether Glycerophospholipids and Their Potential as Therapeutic Agents
Current Organic Chemistry