Insular balance of glutamatergic and GABAergic signaling modulates pain processing

Abstract: Neuroimaging studies of patients with chronic pain have shown that neurotransmitter abnormalities, including increases in glutamate and decreases in GABA, could be responsible for the cortical hyperactivity and hyperalgesia/allodynia observed in some pain conditions. These finding are particularly evident in the insula, a brain region known to play a role in both the sensory–discriminative and the affective–motivational aspects of pain processing. However, clinical studies are not entirely able to determine the directionality of these findings, nor whether they are causal or epiphenomenon. Thus, a set of animal studies was performed to determine whether alterations in glutamate and GABA are the result of injury, the cause of augmented pain processing, or both. Compared with controls, the excitatory neurotransmitters glutamate and aspartate are significantly higher in the rat insula after chronic constriction injury of the sciatic nerve (CCI). The CCI also produced significant increases in allodynia (mechanical and cold), thermal hyperalgesia, and nociceptive aversiveness. Unilateral microinjection of ionotropic glutamate receptor antagonists restored these nociceptive behaviors to preinjury values. Increasing endogenous levels of GABA or enhancing signaling at inhibitory glycinergic receptors had similar effects as the glutamate receptor antagonists. In naive rats, increasing endogenous levels of glutamate, decreasing endogenous levels of GABA, or blocki...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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There is little evidence that the use of cannabinoids can improve symptoms of anxiety, attention-deficit/hyperactivity disorder (ADHD), depression, posttraumatic stress disorder (PTSD), psychosis, or Tourette syndrome, according to areport inLancet Psychiatry.“Cannabinoids are often advocated as a treatment for various mental disorders,” wrote Nicola Black, Ph.D., of the University of New South Wales and colleagues. Doctors and patients “need to be aware of the low quality and quantity of evidence for the effectiveness of medicinal cannabinoids in treating mental disorders and the potential risk of advers...
Source: Psychiatr News - Category: Psychiatry Tags: ADHD anxiety cannabinoids cannabis Deepak Cyril D ’Souza depression meta-analysis Nicola Black psychiatric disorders PTSD Tourette syndrome Source Type: research
This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977).Findings83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or withou...
Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
Although joint pain in rheumatoid arthritis (RA) is conventionally thought to result from inflammation, arthritis pain and joint inflammation are at least partially uncoupled. This suggests that additional pain mechanisms in RA remain to be explored. Here we show that FcγRI, an immune receptor for IgG immune complex (IgG-IC), is expressed in a subpopulation of joint sensory neurons and that, under naive conditions, FcγRI cross-linking by IgG-IC directly activates the somata and peripheral terminals of these neurons to evoke acute joint hypernociception without obvious concurrent joint inflammation. These effect...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Rui Yan1, ShiWan Tao1, HaiYan Liu1, Yu Chen1, JiaBo Shi1, YuYin Yang1, RongXin Zhu1, ZhiJian Yao1,2* and Qing Lu3,4*1Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China2Nanjing Brain Hospital, Medical School of Nanjing University, Nanjing, China3School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, China4Child Development and Learning Science, Key Laboratory of Ministry of Education, Nanjing, ChinaBackground: Major depressive disorders often involve somatic symptoms and have been found to have fundamental differences from non-somatic depressi...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Publication date: Available online 25 April 2019Source: NeuronAuthor(s): Karuna S. Meda, Tosha Patel, Joao M. Braz, Ruchi Malik, Marc L. Turner, Helia Seifikar, Allan I. Basbaum, Vikaas S. SohalSummaryHyperexcitability of the anterior cingulate cortex (ACC) is thought to drive aversion associated with chronic neuropathic pain. Here, we studied the contribution of input from the mediodorsal thalamus (MD) to ACC, using sciatic nerve injury and chemotherapy-induced mouse models of neuropathic pain. Activating MD inputs elicited pain-related aversion in both models. Unexpectedly, excitatory responses of layer V ACC neurons to ...
Source: Neuron - Category: Neuroscience Source Type: research
Conclusion: These findings support the hypothesis that in FM a deteriorated function of cortical inhibition, indexed by a higher SICI parameter, a lower function of the DPMS, together with a higher level of BDNF indicate that FM has different pathological substrates from depression. They suggest that an up-regulation phenomenon of intracortical inhibitory networks associated with a disruption of the DPMS function occurs in FM. Introduction Major depressive disorder (MDD) and fibromyalgia (FM) present overlapped symptoms. Although the connection between these two disorders has not been elucidated yet, the disruption...
Source: Frontiers in Human Neuroscience - Category: Neuroscience Source Type: research
Christophe Duret1,2*, Anne-Gaëlle Grosmaire1 and Hermano Igo Krebs3,4,5,6,7,8 1Centre de Rééducation Fonctionnelle Les Trois Soleils, Médecine Physique et de Réadaptation, Unité de Neurorééducation, Boissise-Le-Roi, France 2Centre Hospitalier Sud Francilien, Neurologie, Corbeil-Essonnes, France 3Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States 4Department of Neurology, University of Maryland, Baltimore, MD, United States 5Department of Physical Medicine and Rehabilitation, Fujita Health University, Nago...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
The Monarch external Trigeminal Nerve Stimulation (eTNS) System made history last week after it became the first device to win a nod from FDA to treat attention deficit hyperactivity disorder (ADHD). It should be noted the technology has had CE mark since 2015. Monarch was developed by NeuroSigma and is indicated to help treat 7 to 12-year-olds suffering from ADHD. What makes this de novo clearance from FDA so significant is that typically pharmaceutical solutions are used to treat patients suffering from the neurological disorder. Monarch is about the size of a cellphone. The device generates a low-level electrical pulse ...
Source: MDDI - Category: Medical Devices Authors: Tags: Digital Health Source Type: news
Discussion Human trafficking is estimated to be the second largest criminal activity in the world after illegal arms trafficking. It affects all nations with an estimated 27 million people of all ages worldwide but only a small number are identified. It is defined by the United Nations as “the recruitment, transfer, harboring, or receipt of persons by means of threat or use of force or other forms of coercions, abduction, fraud, deception, the abuse of power, or a position of vulnerability to achieve the consent of a person, having control over another person, for the purpose of exploitation.” It includes comme...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
In this study, a link between mitochondrial changes and infant temperament has also been suggested. Maternal psychosocial stress and lifetime trauma have been associated with decreased mitochondrial DNA copy number in the placenta (115, 116).IndividualityChronic stress links changes in the epigenetic landscape with health conditions (117). Different cell types are characterized by distinct patterns of gene expression due to developmental, environmental, physiological, and pathological reasons (117). Epigenetic mechanisms affect gene function in a dynamic way as a result of different environmental exposures during fetal dev...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
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