Antinociceptive effects induced through the stimulation of spinal cannabinoid type 2 receptors in chronically inflamed mice

2011 ◽  
Vol 668 (1-2) ◽  
pp. 184-189 ◽  
Author(s):  
Verdad Curto-Reyes ◽  
Tamara Boto ◽  
Agustín Hidalgo ◽  
Luis Menéndez ◽  
Ana Baamonde
Keyword(s):  
Antinociceptive Effects ◽  
Stimulation Of

A determination of excitability changes in dorsal spinocerebellar tract neurons from spike-train analysis

1977 ◽  
Vol 40 (3) ◽  
pp. 626-646 ◽  
Author(s):  
C. K. Knox ◽  
S. Kubota ◽  
R. E. Poppele
Keyword(s):  
Spike Train ◽  
Afferent Input ◽  
Complex Interactions ◽  
Group I ◽  
Long Latency ◽  
Cross Correlation Analysis ◽  
Output Spike ◽  
Type 3 ◽  
Stimulation Of

1. Responses of DSCT neurons to random electrical stimulation of peripheral nerves of the hindleg at group I intensity were studied using cross-correlation analysis of the output spike train with the stimulus. Three types of response were found: type 1 was due to monosynaptic activation of DSCT cells, type 2 resulted from inhibition of those cells, and type 3 was due to a long-latency excitation that was probably polysynaptic. 2. Most of the units studied responded to stimulation of both proximal and distal flexor and extensor nerves. The extensive convergence of afferent input on DSCT cells is much greater than has been observed previously, with type 2 and type 3 responses totaling 80% of the observed responses. We attribute this to the sensitivity of the analysis in detecting small changes in postsynaptic excitability. 3. The results of the study, particularly the derivation of postsynaptic excitability changes, generally confirm those of earlier work employing intracellular recording. 4. By varying stimulus rate and stimulus intensity in the group 1 range and simulating the resulting correlations, we conclude that excitability changes in DSCT cells are the net result of complex interactions involving excitation and inhibition. A summary of these findings is presented as a model for the minimum circuitry necessary to account for the observed behavior.

scholarly journals Differential expression and regulation of ryanodine receptor and myo-inositol 1,4,5-trisphosphate receptor Ca2+ release channels in mammalian tissues and cell lines

1997 ◽  
Vol 327 (1) ◽  
pp. 251-258 ◽  
Author(s):  
John J. MACKRILL ◽  
R. A. John CHALLISS ◽  
D. A. O'CONNELL ◽  
F. Anthony LAI ◽  
Stefan R. NAHORSKI
Keyword(s):  
Cell Lines ◽  
Mammalian Cell ◽  
Release Channel ◽  
Chronic Stimulation ◽  
Channel Proteins ◽  
Mammalian Cell Lines ◽  
Rabbit Tissues ◽  
Stimulation Of

Ryanodine receptors (RyRs) and Ins(1,4,5)P3 receptors (Ins(1,4,5)P3Rs) represent two multigene families of channel proteins that mediate the release of Ca2+ ions from intracellular stores. In the present study, the expression patterns of these channel proteins in mammalian cell lines and tissues were investigated by using isoform-specific antibodies. All cell lines examined expressed two or more Ins(1,4,5)P3R isoforms, with the type 1 Ins(1,4,5)P3R being ubiquitous. RyR isoforms were detected in only six out of eight cell lines studied. Similarly, of the nine rabbit tissues examined, RyR protein expression was detected only in brain, heart, skeletal muscle and uterus. Specific [3H]ryanodine binding was found in a number of rabbit tissues, although it was not detected in mammalian cell lines. Subcellular fractionation of SH-SY5Y human neuroblastomas revealed that the type 2 RyR and type 1 Ins(1,4,5)P3R co-localize among the fractions of a sucrose-cushion separation of crude microsomal membrane fractions. Manipulation of SH-SY5Y cells by chronic stimulation of muscarinic acetylcholine receptor (mAChR) results in a decrease in their type 1 Ins(1,4,5)P3R levels but not in the abundance of the type 2 RyR. Differentiation of these neuroblastomas by using retinoic acid did not detectably alter their expression of Ca2+-release channel proteins. Finally, differentiation of BC3H1 cells affects the expression of their Ca2+-release channel proteins in an isoform-specific manner. In summary, this study demonstrates that mammalian cell lines display distinct patterns of Ca2+-release channel protein expression. The abundance of these proteins is differentially regulated during phenotypic modifications of a cell, such as differentiation or chronic stimulation of mAChR.

scholarly journals A Sustained Activation of Pancreatic NMDARs Is a Novel Factor of β-Cell Apoptosis and Dysfunction

Endocrinology ◽  
2017 ◽  
Vol 158 (11) ◽  
pp. 3900-3913 ◽  
Author(s):  
Xiao-Ting Huang ◽  
Shao-Jie Yue ◽  
Chen Li ◽  
Yan-Hong Huang ◽  
Qing-Mei Cheng ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Apoptosis ◽  
Cell Function ◽  
Cell Mass ◽  
Nuclear Factor Κb ◽  
Β Cells ◽  
Β Cell ◽  
Stimulation Of ◽  
Sustained Activation

Abstract Type 2 diabetes, which features β-cell failure, is caused by the decrease of β-cell mass and insulin secretory function. Current treatments fail to halt the decrease of functional β-cell mass. Strategies to prevent β-cell apoptosis and dysfunction are highly desirable. Recently, our group and others have reported that blockade of N-methyl-d-aspartate receptors (NMDARs) in the islets has been proposed to prevent the progress of type 2 diabetes through improving β-cell function. It suggests that a sustained activation of the NMDARs may exhibit deleterious effect on β-cells. However, the exact functional impact and mechanism of the sustained NMDAR stimulation on islet β-cells remains unclear. Here, we identify a sustained activation of pancreatic NMDARs as a novel factor of apoptotic β-cell death and function. The sustained treatment with NMDA results in an increase of intracellular [Ca2+] and reactive oxygen species, subsequently induces mitochondrial membrane potential depolarization and a decrease of oxidative phosphorylation expression, and then impairs the mitochondrial function of β-cells. NMDA specifically induces the mitochondrial-dependent pathway of apoptosis in β-cells through upregulation of the proapoptotic Bim and Bax, and downregulation of antiapoptotic Bcl-2. Furthermore, a sustained stimulation of NMDARs impairs β-cell insulin secretion through decrease of pancreatic duodenal homeobox-1 (Pdx-1) and adenosine triphosphate synthesis. The activation of nuclear factor–κB partly contributes to the reduction of Pdx-1 expression induced by overstimulation of NMDARs. In conclusion, we show that the sustained stimulation of NMDARs is a novel mediator of apoptotic signaling and β-cell dysfunction, providing a mechanistic insight into the pathological role of NMDARs activation in diabetes.

Control of pain initiation by endogenous cannabinoids

2018 ◽  
Author(s):  
Andrea G. Hohmann
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peripheral Mechanism ◽  
Antinociceptive Effects ◽  
The Central Nervous System ◽  
Cns Side Effects ◽  
Endogenous Cannabinoids ◽  
Redundant Functions

The landmark paper discussed in this chapter, published by Calignano et al. in 1998, focuses on the control of pain initiation by endogenous cannabinoids. In the paper, analgesic lipid mediators are shown to be present in peripheral paw tissue where they control the ability of pain signals to ascend to the central nervous system (CNS). Anandamide acts through a peripheral mechanism to suppress inflammatory pain via cannabinoid type 1 receptors. Palmitoylethanolamine, subsequently identified as an endogenous ligand for peroxisome proliferator-activated receptor-α‎, produces peripheral antinociceptive effects via a mechanism similar to that for the cannabinoid type 2 receptor. These lipids do not serve redundant functions and, in combination, produce synergistic antinociceptive effects. These observations suggested that drug-development efforts targeting peripheral control of pain may elucidate improved pharmacotherapies that lack the unwanted CNS side effects of current treatments.

scholarly journals Long-Lasting Anti-Inflammatory and Antinociceptive Effects of Acute Ammonium Glycyrrhizinate Administration: Pharmacological, Biochemical, and Docking Studies

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2453 ◽  
Author(s):  
Francesco Maione ◽  
Paola Minosi ◽  
Amalia Di Giannuario ◽  
Federica Raucci ◽  
Maria Giovanna Chini ◽  
...  
Keyword(s):  
Animal Models ◽  
Antinociceptive Effect ◽  
Binding Pocket ◽  
Docking Studies ◽  
Prostaglandin E ◽  
Single Administration ◽  
Antinociceptive Effects ◽  
Anti Inflammatory

The object of the study was to estimate the long-lasting effects induced by ammonium glycyrrhizinate (AG) after a single administration in mice using animal models of pain and inflammation together with biochemical and docking studies. A single intraperitoneal injection of AG was able to produce anti-inflammatory effects in zymosan-induced paw edema and peritonitis. Moreover, in several animal models of pain, such as the writhing test, the formalin test, and hyperalgesia induced by zymosan, AG administered 24 h before the tests was able to induce a strong antinociceptive effect. Molecular docking studies revealed that AG possesses higher affinity for microsomal prostaglandin E synthase type-2 compared to type-1, whereas it seems to locate better in the binding pocket of cyclooxygenase (COX)-2 compared to COX-1. These results demonstrated that AG induced anti-inflammatory and antinociceptive effects until 24–48 h after a single administration thanks to its ability to bind the COX/mPGEs pathway. Taken together, all these findings highlight the potential use of AG for clinical treatment of pain and/or inflammatory-related diseases.

scholarly journals Cannabinoid Modulation of Cutaneous Aδ Nociceptors During Inflammation

2008 ◽  
Vol 100 (5) ◽  
pp. 2794-2806 ◽  
Author(s):  
Carl Potenzieri ◽  
Thaddeus S. Brink ◽  
Cholawat Pacharinsak ◽  
Donald A. Simone
Keyword(s):  
Receptor Antagonist ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Evoked Responses ◽  
Intraplantar Injection ◽  
Withdrawal Threshold ◽  
Antinociceptive Effects ◽  
Electrophysiological Studies ◽  
Stimulation Of

Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB1 and CB2). However, it is currently unknown if cannabinoids alter the response properties of nociceptors. In the present study, correlative behavioral and in vivo electrophysiological studies were conducted to determine if peripheral administration of the cannabinoid receptor agonists arachidonyl-2′-chloroethylamide (ACEA) or (R)-(+)-methanandamide (methAEA) could attenuate mechanical allodynia and hyperalgesia, and decrease mechanically evoked responses of Aδ nociceptors. Twenty-four hours after intraplantar injection of complete Freund's adjuvant (CFA), rats exhibited allodynia (decrease in paw withdrawal threshold) and hyperalgesia (increase in paw withdrawal frequency), which were attenuated by both ACEA and methAEA. The antinociceptive effects of these cannabinoids were blocked by co-administration with the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) but not with the CB2 receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-y l](4-methoxyphenyl)methanone (AM630). ACEA and methAEA did not produce antinociception under control, non-inflamed conditions 24 h after intraplantar injection of saline. In parallel studies, recordings were made from cutaneous Aδ nociceptors from inflamed or control, non-inflamed skin. Both ACEA and methAEA decreased responses evoked by mechanical stimulation of Aδ nociceptors from inflamed skin but not from non-inflamed skin, and this decrease was blocked by administration of the CB1 receptor antagonist AM251. These results suggest that attenuation of mechanically evoked responses of Aδ nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB1 receptors during inflammation.

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