Abstract
Long-term potentiation (LTP), referring to a lasting increase in efficacy of synaptic transmission, is a common mechanism of memory storage in central nervous system (CNS). LTP at C-fiber synapses in spinal dorsal horn is considered as a synaptic model of pathological pain, as the spinal LTP is only induced by noxious electrical and natural stimuli but not by innoxious ones and LTPinducible stimulation is capable of leading to lasting behavioral signs of pathological pain in human and in animals. The molecular mechanisms of spinal LTP at C-fiber synapses are similar to hippocampal LTP in following aspects. Induction of LTP depends on postsynaptic Ca2+ rise resulting from opening of N-methyl-D-aspartate channels (NMDA) and voltage-gated calcium channels (VGCCs), and Ca2+ release from intracellular store; Early-phase LTP (<3h) needs activation of intracellular protein kinase A (PKA), protein kinase C (PKC), calcium/calmodulin-dependent protein kinase II (CaMKII), phospholipase C (PLC) and release of nitric oxide (NO); Late-phase LTP (>3h) is dependent on de novo protein synthesis; Activation of either dopamine D1 receptors or PKA, and extrogenous brain-derived neurotrophic factor (BDNF) or ATP directly induces late-phase LTP. Therefore, the drugs targeting at the above molecules may impair memory function of hippocampus. The striking difference between hippocampal LTP and spinal LTP at C-fiber synapses is that activation of glial cells and the over–expression of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin– beta (IL-1β), inhibit LTP in hippocampus, but promote LTP in spinal dorsal horn. The drugs targeting at the neuroinflammatory process may not only attenuate pathological pain but also improve memory in hippocampus.
Keywords: Long-term potentiation, C-fiber, spinal dorsal horn, pathological pain, hippocampus, proinflammatory cytokine.
Current Pharmaceutical Design
Title:Long-term Potentiation at Spinal C-fiber Synapses: A Target for Pathological Pain
Volume: 21 Issue: 7
Author(s): Xian-Guo Liu and Li-Jun Zhou
Affiliation:
Keywords: Long-term potentiation, C-fiber, spinal dorsal horn, pathological pain, hippocampus, proinflammatory cytokine.
Abstract: Long-term potentiation (LTP), referring to a lasting increase in efficacy of synaptic transmission, is a common mechanism of memory storage in central nervous system (CNS). LTP at C-fiber synapses in spinal dorsal horn is considered as a synaptic model of pathological pain, as the spinal LTP is only induced by noxious electrical and natural stimuli but not by innoxious ones and LTPinducible stimulation is capable of leading to lasting behavioral signs of pathological pain in human and in animals. The molecular mechanisms of spinal LTP at C-fiber synapses are similar to hippocampal LTP in following aspects. Induction of LTP depends on postsynaptic Ca2+ rise resulting from opening of N-methyl-D-aspartate channels (NMDA) and voltage-gated calcium channels (VGCCs), and Ca2+ release from intracellular store; Early-phase LTP (<3h) needs activation of intracellular protein kinase A (PKA), protein kinase C (PKC), calcium/calmodulin-dependent protein kinase II (CaMKII), phospholipase C (PLC) and release of nitric oxide (NO); Late-phase LTP (>3h) is dependent on de novo protein synthesis; Activation of either dopamine D1 receptors or PKA, and extrogenous brain-derived neurotrophic factor (BDNF) or ATP directly induces late-phase LTP. Therefore, the drugs targeting at the above molecules may impair memory function of hippocampus. The striking difference between hippocampal LTP and spinal LTP at C-fiber synapses is that activation of glial cells and the over–expression of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin– beta (IL-1β), inhibit LTP in hippocampus, but promote LTP in spinal dorsal horn. The drugs targeting at the neuroinflammatory process may not only attenuate pathological pain but also improve memory in hippocampus.
Export Options
About this article
Cite this article as:
Liu Xian-Guo and Zhou Li-Jun, Long-term Potentiation at Spinal C-fiber Synapses: A Target for Pathological Pain, Current Pharmaceutical Design 2015; 21 (7) . https://dx.doi.org/10.2174/1381612820666141027115949
DOI https://dx.doi.org/10.2174/1381612820666141027115949 |
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
-
Melatonin, its Metabolites and its Synthetic Analogs as Multi-Faceted Compounds: Antioxidant, Prooxidant and Inhibitor of Bioactivation Reactions
Current Medicinal Chemistry Drugs Treatment of Pain in Multiple Sclerosis
Current Clinical Pharmacology Functional Neuroproteomics: An Imperative Approach for Unravelling Protein Implicated Complexities of Brain
CNS & Neurological Disorders - Drug Targets Triamcinolone Acetonide Inhibits p38MAPK Activation and Neuronal Apoptosis in Early Diabetic Retinopathy
Current Molecular Medicine 5-HT3 Receptors: A Potential Therapeutic Target for Epilepsy
Current Neuropharmacology Hematopoietic Stem Cells Therapies
Current Stem Cell Research & Therapy Targeted Drug Delivery and Imaging Using Mobile Milli/Microrobots: A Promising Future Towards Theranostic Pharmaceutical Design
Current Pharmaceutical Design Spastin Interacts with CRMP2 to Regulate Neurite Outgrowth by Controlling Microtubule Dynamics through Phosphorylation Modifications
CNS & Neurological Disorders - Drug Targets The Neurotrophic and Antiangiogenic Functions of PEDF: A Reflection of its Variable Phosphorylation States
Current Genomics Mesenchymal Stem Cells in the Umbilical Cord: Phenotypic Characterization, Secretome and Applications in Central Nervous System Regenerative Medicine
Current Stem Cell Research & Therapy Pituitary Adenylate Cyclase-Activating Polypeptide: Focus on Structure- Activity Relationships of a Neuroprotective Peptide
Current Medicinal Chemistry Induced Pluripotent Stem Cells in Regenerative Medicine and Disease Modeling
Current Stem Cell Research & Therapy Peripheral TRPV1 Receptors As Targets for Drug Development: New Molecules and Mechanisms
Current Pharmaceutical Design Natural Products for the Treatment of Neurodegenerative Diseases
Current Medicinal Chemistry Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19
Current Neuropharmacology Neural Differentiation and Therapeutic Potential of Adipose Tissue Derived Stem Cells
Current Stem Cell Research & Therapy The Peri-operative Management of the Rheumatoid Patient Undergoing Total Knee Arthroplasty: A Review of Literature
Current Rheumatology Reviews VIP in Neurological Diseases: More Than A Neuropeptide
Endocrine, Metabolic & Immune Disorders - Drug Targets Management of Spasticity in Progressive Multiple Sclerosis: Efficacy of Repeated Intrathecal Triamcinolone Acetonide Administration
Current Pharmaceutical Design Free Fatty Acids: Circulating Contributors of Metabolic Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry