Abstract
Prokineticin1 and prokineticin2 belong to a new family of chemokines identified in several species including mammals and characterized by the presence of five disulfide bridges.
These proteins signal through two G-coupled receptors (prokineticin-receptor1 and prokineticin- receptor2) widely expressed in all tissues and involved in a large spectrum of biological activities, including angiogenesis, hematopoiesis, immune processes, inflammation and nociceptive transmission. Prokineticin2 is overexpressed in inflamed tissues and has a crucial role in neutrophil dependent inflammation and hypernociception.
Following tissue inflammation, peripheral nerve injury, cancer, bone metastasis the expression of prokineticin2 and of the prokineticin-receptor2 is increased also within dorsal root ganglia and spinal cord. Prokineticin receptors, highly expressed in nociceptor endings and dorsal root ganglia, exert a tonic activation of TRPV1 and TRPA1 contributing to peripheral sensitization. Prokineticin2-induces activation of the prokineticin receptors in the spinal dorsal horn and in activated astrocytes contributes to central sensitization and maintains chronic and neuropathic pain.
Prokineticin2, acting on prokineticin receptors on monocytes, macrophages and dendritic cells, induces chemotaxis and release of inflammatory and pronociceptive cytokines. Hence, the prokineticin system represents a novel therapeutic target in chronic pain conditions. Evaluation of the mechanism of action of prokineticin2 and the potential effectiveness of its inhibition is discussed.
Keywords: Prokineticin system, chronic pain, inflammation, G-coupled receptors, chemokines, PROK system.
Current Medicinal Chemistry
Title:Targeting the Prokineticin System to Control Chronic Pain and Inflammation
Volume: 25 Issue: 32
Author(s): Lucia Negri*Daniela Maftei
Affiliation:
- Department of Physiology and Pharmacology "Vittorio Erspamer", Faculty of Medicine, Sapienza University of Roma, Roma,Italy
Keywords: Prokineticin system, chronic pain, inflammation, G-coupled receptors, chemokines, PROK system.
Abstract: Prokineticin1 and prokineticin2 belong to a new family of chemokines identified in several species including mammals and characterized by the presence of five disulfide bridges.
These proteins signal through two G-coupled receptors (prokineticin-receptor1 and prokineticin- receptor2) widely expressed in all tissues and involved in a large spectrum of biological activities, including angiogenesis, hematopoiesis, immune processes, inflammation and nociceptive transmission. Prokineticin2 is overexpressed in inflamed tissues and has a crucial role in neutrophil dependent inflammation and hypernociception.
Following tissue inflammation, peripheral nerve injury, cancer, bone metastasis the expression of prokineticin2 and of the prokineticin-receptor2 is increased also within dorsal root ganglia and spinal cord. Prokineticin receptors, highly expressed in nociceptor endings and dorsal root ganglia, exert a tonic activation of TRPV1 and TRPA1 contributing to peripheral sensitization. Prokineticin2-induces activation of the prokineticin receptors in the spinal dorsal horn and in activated astrocytes contributes to central sensitization and maintains chronic and neuropathic pain.
Prokineticin2, acting on prokineticin receptors on monocytes, macrophages and dendritic cells, induces chemotaxis and release of inflammatory and pronociceptive cytokines. Hence, the prokineticin system represents a novel therapeutic target in chronic pain conditions. Evaluation of the mechanism of action of prokineticin2 and the potential effectiveness of its inhibition is discussed.
Export Options
About this article
Cite this article as:
Negri Lucia *, Maftei Daniela, Targeting the Prokineticin System to Control Chronic Pain and Inflammation, Current Medicinal Chemistry 2018; 25 (32) . https://dx.doi.org/10.2174/0929867324666170713102514
DOI https://dx.doi.org/10.2174/0929867324666170713102514 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Innate Immune Surveillance in the Central Nervous System Following Legionella pneumophila Infection
CNS & Neurological Disorders - Drug Targets The Innate Immunity in Alzheimer Disease- Relevance to Pathogenesis and Therapy
Current Pharmaceutical Design Comparative Genomics for the Investigation of Autoimmune Diseases
Current Pharmaceutical Design Potential Crossreactivity of Human Immune Responses Against HCMV Glycoprotein B
Current Drug Discovery Technologies Editorial [Hot topic: Role of Inflammation in Neurological and Psychiatric Disorders (Guest Editor: Mohtashem Samsam)]
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cancer Prevention with Promising Natural Products: Mechanisms of Action and Molecular Targets
Anti-Cancer Agents in Medicinal Chemistry Immunomodulation in Trichinellosis: Does Trichinella Really Escape the Host Immune System?
Endocrine, Metabolic & Immune Disorders - Drug Targets Current Proposed Mechanisms of Action of Intravenous Immunoglobulins in Inflammatory Neuropathies
Current Neuropharmacology Activation and Costimulation of Intestinal T Cells: Independent and Collaborative Involvement of CD43, OX40, and Ly-6C
Current Immunology Reviews (Discontinued) Experimental Strategies in Autoimmunity: Antagonists of Cytokines and their Receptors, Nanocarriers, Inhibitors of Immunoproteasome, Leukocyte Migration and Protein Kinases
Current Pharmaceutical Design An Overview of Notch Signaling in Adult Tissue Renewal and Maintenance
Current Alzheimer Research Nanostructures for Drug Delivery to the Brain
Current Medicinal Chemistry Toll-Like Receptors: Sensor Molecules for Detecting Damage to the Nervous System
Current Protein & Peptide Science Importance of ABC Transporters in Drug Development
Current Pharmaceutical Design Calorie Restriction and Dietary Restriction Mimetics: A Strategy for Improving Healthy Aging and Longevity
Current Pharmaceutical Design The Role of B Cells in Multiple Sclerosis: Implications for B-Cell-Targeted Therapy
Current Medicinal Chemistry Protease-Activated Receptor 2: Are Common Functions in Glial and Immune Cells Linked to Inflammation-Related CNS Disorders?
Current Drug Targets Anticancer Properties of the IL-12 Family - Focus on Colorectal Cancer
Current Medicinal Chemistry Central Nervous System Involvement in Pediatric Rheumatic Diseases: Current Concepts in Treatment
Current Pharmaceutical Design Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms
Anti-Cancer Agents in Medicinal Chemistry