scholarly journals The Central Role of Glia in Pathological Pain and the Potential of Targeting the Cannabinoid 2 Receptor for Pain Relief

2011 ◽  
Vol 2011 ◽  
pp. 1-19 ◽  
Author(s):  
Jenny L. Wilkerson ◽  
Erin D. Milligan
Keyword(s):  
Pain Relief ◽  
Cannabinoid Receptor ◽  
Receptor Subtype ◽  
Pain Processing ◽  
Neuronal Mechanisms ◽  
Cannabinoid Compounds ◽  
The Central Nervous System ◽  
Pathological Pain ◽  
Novel Therapeutic

Under normal conditions, acute pain processing consists of well-characterized neuronal signaling events. When dysfunctional pain signaling occurs, pathological pain ensues. Glial activation and their released factors participate in the mediation of pathological pain. The use of cannabinoid compounds for pain relief is currently an area of great interest for both basic scientists and physicians. These compounds, bind mainly either the cannabinoid receptor subtype 1 (CB1R) or cannabinoid receptor subtype 2 (CB2R) and are able to modulate pain. Although cannabinoids were initially only thought to modulate pain via neuronal mechanisms within the central nervous system, strong evidence now supports that CB2R cannabinoid compounds are capable of modulating glia, (e.g. astrocytes and microglia) for pain relief. However, the mechanisms underlying cannabinoid receptor-mediated pain relief remain largely unknown. An emerging body of evidence supports that CB2R agonist compounds may prove to be powerful novel therapeutic candidates for the treatment of chronic pain.

scholarly journals Social Isolation: How Can the Effects on the Cholinergic System Be Isolated?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jaromir Myslivecek
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Isolation ◽  
Cholinergic System ◽  
System Response ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Cholinergic Signaling ◽  
The Central Nervous System

Social species form organizations that support individuals because the consequent social behaviors help these organisms survive. The isolation of these individuals may be a stressor. We reviewed the potential mechanisms of the effects of social isolation on cholinergic signaling and vice versa how changes in cholinergic signaling affect changes due to social isolation.There are two important problems regarding this topic. First, isolation schemes differ in their duration (1–165 days) and initiation (immediately after birth to adulthood). Second, there is an important problem that is generally not considered when studying the role of the cholinergic system in neurobehavioral correlates: muscarinic and nicotinic receptor subtypes do not differ sufficiently in their affinity for orthosteric site agonists and antagonists. Some potential cholinesterase inhibitors also affect other targets, such as receptors or other neurotransmitter systems. Therefore, the role of the cholinergic system in social isolation should be carefully considered, and multiple receptor systems may be involved in the central nervous system response, although some subtypes are involved in specific functions. To determine the role of a specific receptor subtype, the presence of a specific subtype in the central nervous system should be determined using search in knockout studies with the careful application of specific agonists/antagonists.

Osteocalcin: A Protein Hormone Connecting Metabolism, Bone and Testis Function

2020 ◽  
Vol 27 (12) ◽  
pp. 1268-1275
Author(s):  
Luca De Toni ◽  
Kenda Jawich ◽  
Maurizio De Rocco Ponce ◽  
Andrea Di Nisio ◽  
Carlo Foresta
Keyword(s):  
Experimental Data ◽  
Male Fertility ◽  
Endocrine Function ◽  
Protective Effects ◽  
Original Function ◽  
Endocrine Organ ◽  
The Central Nervous System ◽  
Depressive States ◽  
Novel Therapeutic

During the last decade, the disclosure of systemic effects of osteocalcin (OCN) in its undercarboxylated form contributed to switch the concept of bone from a merely structural apparatus to a fully endocrine organ involved in the regulation of systemic functions. Since that time, the role of OCN as osteokine has been more and more widened appreciated and detailed by the major use of animal models, starting from the original function in the bone extracellular matrix as Gla-protein and spanning from the protective effects towards weight gain, insulin sensitivity and glucose homeostasis, to the anabolic and metabolic roles in skeletal muscle, to the stimulating effects on the testis endocrine function and male fertility, to the most recent preservation from anxious and depressive states through a direct activity on the central nervous system. In this review, experimental data supporting the inter-organ communication roles of this protein are discussed, together with the available data supporting the consistency between experimental data obtained in animals and those reported in humans. In addition, a specific session has been devoted to the possible significance the OCN as a template agonist on its receptor GPRC6A, for the development of novel therapeutic and pharmacological approaches for the treatment of dismetabolic states and male infertility.

scholarly journals Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Seung-In Choi ◽  
Ji Yeon Lim ◽  
Sungjae Yoo ◽  
Hyun Kim ◽  
Sun Wook Hwang
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Pain Mechanisms ◽  
Historical Perspectives ◽  
Pain Pathway ◽  
Central Regions ◽  
The Central Nervous System ◽  
Pathological Pain ◽  
Synaptic Mechanisms

TRPV1 is well known as a sensor ion channel that transduces a potentially harmful environment into electrical depolarization of the peripheral terminal of the nociceptive primary afferents. Although TRPV1 is also expressed in central regions of the nervous system, its roles in the area remain unclear. A series of recent reports on the spinal cord synapses have provided evidence that TRPV1 plays an important role in synaptic transmission in the pain pathway. Particularly, in pathologic pain states, TRPV1 in the central terminal of sensory neurons and interneurons is suggested to commonly contribute to pain exacerbation. These observations may lead to insights regarding novel synaptic mechanisms revealing veiled roles of spinal cord TRPV1 and may offer another opportunity to modulate pathological pain by controlling TRPV1. In this review, we introduce historical perspectives of this view and details of the recent promising results. We also focus on extended issues and unsolved problems to fully understand the role of TRPV1 in pathological pain. Together with recent findings, further efforts for fine analysis of TRPV1’s plastic roles in pain synapses at different levels in the central nervous system will promote a better understanding of pathologic pain mechanisms and assist in developing novel analgesic strategies.

S100B raises the alert in subarachnoid hemorrhage

2016 ◽  
Vol 27 (7) ◽  
pp. 745-759 ◽  
Author(s):  
Zhao Zhong Chong
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Calcium Binding ◽  
Intracellular Signaling ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
Protein S100b ◽  
Novel Therapeutic

AbstractSubarachnoid hemorrhage (SAH) is a devastating disease with high mortality and mobility, the novel therapeutic strategies of which are essentially required. The calcium binding protein S100B has emerged as a brain injury biomarker that is implicated in pathogenic process of SAH. S100B is mainly expressed in astrocytes of the central nervous system and functions through initiating intracellular signaling or via interacting with cell surface receptor, such as the receptor of advanced glycation end products. The biological roles of S100B in neurons have been closely associated with its concentrations, resulting in either neuroprotection or neurotoxicity. The levels of S100B in the blood have been suggested as a biomarker to predict the progress or the prognosis of SAH. The role of S100B in the development of cerebral vasospasm and brain damage may result from the induction of oxidative stress and neuroinflammation after SAH. To get further insight into mechanisms underlying the role of S100B in SAH based on this review might help us to find novel therapeutic targets for SAH.

scholarly journals Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities

2021 ◽  
Vol 22 (11) ◽  
pp. 6126
Author(s):  
Magdalena Groblewska ◽  
Barbara Mroczko
Keyword(s):  
Normal Development ◽  
Malignant Tumors ◽  
Antiangiogenic Therapy ◽  
Primary Tumors ◽  
Pubmed Database ◽  
Multistep Process ◽  
The Central Nervous System ◽  
Antiangiogenic Factors ◽  
Novel Therapeutic

Angiogenesis, a complex, multistep process of forming new blood vessels, plays crucial role in normal development, embryogenesis, and wound healing. Malignant tumors characterized by increased proliferation also require new vasculature to provide an adequate supply of oxygen and nutrients for developing tumor. Gliomas are among the most frequent primary tumors of the central nervous system (CNS), characterized by increased new vessel formation. The processes of neoangiogenesis, necessary for glioma development, are mediated by numerous growth factors, cytokines, chemokines and other proteins. In contrast to other solid tumors, some biological conditions, such as the blood–brain barrier and the unique interplay between immune microenvironment and tumor, represent significant challenges in glioma therapy. Therefore, the objective of the study was to present the role of various proangiogenic factors in glioma angiogenesis as well as the differences between normal and tumoral angiogenesis. Another goal was to present novel therapeutic options in oncology approaches. We performed a thorough search via the PubMed database. In this paper we describe various proangiogenic factors in glioma vasculature development. The presented paper also reviews various antiangiogenic factors necessary in maintaining equilibrium between pro- and antiangiogenic processes. Furthermore, we present some novel possibilities of antiangiogenic therapy in this type of tumors.

scholarly journals The Emerging Role of Microglia in Neuromyelitis Optica

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingjun Chen ◽  
Dale B. Bosco ◽  
Yanlu Ying ◽  
Dai-Shi Tian ◽  
Long-Jun Wu
Keyword(s):  
Animal Models ◽  
Neuromyelitis Optica ◽  
Microglial Activation ◽  
Molecular Mechanisms ◽  
Water Channel ◽  
Therapeutic Approaches ◽  
The Central Nervous System ◽  
Water Channel Protein ◽  
Novel Therapeutic

Neuromyelitis optica (NMO) is an autoantibody-triggered neuro-inflammatory disease which preferentially attacks the spinal cord and optic nerve. Its defining autoantibody is specific for the water channel protein, aquaporin‐4 (AQP4), which primarily is localized at the end-feet of astrocytes. Histopathology studies of early NMO lesions demonstrated prominent activation of microglia, the resident immune sentinels of the central nervous system (CNS). Significant microglial reactivity is also observed in NMO animal models induced by introducing AQP4-IgG into the CNS. Here we review the potential roles for microglial activation in human NMO patients as well as different animal models of NMO. We will focus primarily on the molecular mechanisms underlying microglial function and microglia-astrocyte interaction in NMO pathogenesis. Understanding the role of microglia in NMO pathology may yield novel therapeutic approaches for this disease.

scholarly journals Investigating the Function of Adult DRG Neuron Axons Using an In Vitro Microfluidic Culture System

Micromachines ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1317
Author(s):  
Rahul Atmaramani ◽  
Srivennela Veeramachaneni ◽  
Liz Valeria Mogas ◽  
Pratik Koppikar ◽  
Bryan J. Black ◽  
...  
Keyword(s):  
Action Potentials ◽  
Critical Role ◽  
Mrna Translation ◽  
In Vitro Models ◽  
Drg Neuron ◽  
Genetic Perturbations ◽  
The Central Nervous System ◽  
Pathological Pain

A critical role of the peripheral axons of nociceptors of the dorsal root ganglion (DRG) is the conduction of all-or-nothing action potentials from peripheral nerve endings to the central nervous system for the perception of noxious stimuli. Plasticity along multiple sites along the pain axis has now been widely implicated in the maladaptive changes that occur in pathological pain states such as neuropathic and inflammatory pain. Notably, increasing evidence suggests that nociceptive axons actively participate through the local expression of ion channels, receptors, and signal transduction molecules through axonal mRNA translation machinery that is independent of the soma component. In this report, we explore the sensitization of sensory neurons through the treatment of compartmentalized axon-like structures spanning microchannels that have been treated with the cytokine IL-6 and, subsequently, capsaicin. These data demonstrate the utility of isolating DRG axon-like structures using microfluidic systems, laying the groundwork for constructing the complex in vitro models of cellular networks that are involved in pain signaling for targeted pharmacological and genetic perturbations.

Sign in / Sign up

Export Citation Format

Share Document