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
-
In Vitro and In Vivo Neuroprotective Effects of Etifoxine in β-Amyloidinduced Toxicity Models
CNS & Neurological Disorders - Drug Targets Alzheimers Disease Drug Development: Old Problems Require New Priorities
CNS & Neurological Disorders - Drug Targets Nicotinic Acetylcholine Receptor Interaction with β -Amyloid: Molecular, Cellular, and Physiological Consequences
Current Alzheimer Research <i>Ammoides verticillata</i> Essential Oil as Biocontrol Agent of Selected Fungi and Pest of Olive Tree
Recent Patents on Food, Nutrition & Agriculture Homology Modeling Inspired Synthesis of 5-HT2A Receptor Inhibitors: A Diazepine Analogue of the Atypical Antipsychotic JL13
Central Nervous System Agents in Medicinal Chemistry Diabetic Theory in Anti-Alzheimer’s Drug Research and Development - Part 1: Therapeutic Potential of Antidiabetic Agents
Current Medicinal Chemistry Axonopathy Likely Initiates Neuropathological Processes Via a Mechanism of Axonal Leakage in Alzheimer's Mouse Models
Current Molecular Medicine A Survey of Recent Patents on CB2 Agonists in the Management of Pain
Recent Patents on CNS Drug Discovery (Discontinued) Progress and Prospects of Stem Cells in Treatment of Drug Resistant Tuberculosis
Current Respiratory Medicine Reviews Peganum harmala L. Differentially Modulates Cytochrome P450 Gene Expression in Human Hepatoma HepG2 Cells
Drug Metabolism Letters Current Progresses on Nanodelivery Systems for the Treatment of Neuropsychiatric Diseases: Alzheimer’s and Schizophrenia
Current Pharmaceutical Design Hippocampal and Amygdalar Morphological Abnormalities in Alzheimer’s Disease Based on Three Chinese MRI Datasets
Current Alzheimer Research The Gene Expression Profiles of Medulloblastoma Cell Lines Resistant to Preactivated Cyclophosphamide
Current Cancer Drug Targets Antioxidant Therapy Alters Brain MAPK-JNK and BDNF Signaling Path-ways in Experimental Diabetes Mellitu s
Current Neurovascular Research In the Rush for Green Gold: Can Green Tea Delay Age-Progressive Brain Neurodegeneration?
Recent Patents on CNS Drug Discovery (Discontinued) Editorial [ Monitoring Drugs of Abuse in Wastewater and Air ]
Current Drug Abuse Reviews Therapeutic Benefit and Biological Importance of Ginkgetin in the Medicine: Medicinal Importance, Pharmacological Activities and Analytical Aspects
Current Bioactive Compounds Change in Body Mass Index Before and After Alzheimer’s Disease Onset
Current Alzheimer Research The Role of MRI and PET/SPECT in Alzheimers Disease
Current Topics in Medicinal Chemistry Protein Aggregation in Alzheimers Disease and Other Neoropathological Disorders
Current Alzheimer Research