Neuroinflammation and Central Sensitization in Chronic and Widespread Pain

Anesthesiology, Journal Year: 2018, Volume and Issue: 129(2), P. 343 - 366

Published: Feb. 16, 2018

Abstract Chronic pain is maintained in part by central sensitization, a phenomenon of synaptic plasticity, and increased neuronal responsiveness pathways after painful insults. Accumulating evidence suggests that sensitization also driven neuroinflammation the peripheral nervous system. A characteristic feature activation glial cells, such as microglia astrocytes, spinal cord brain, leading to release proinflammatory cytokines chemokines. Recent studies suggest chemokines are powerful neuromodulators play sufficient role inducing hyperalgesia allodynia system administration. Sustained increase promotes chronic widespread affects multiple body sites. Thus, drives via sensitization. We discuss sex-dependent glial/immune signaling new therapeutic approaches control for resolution pain.

Language: Английский

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Purinergic Signalling: Therapeutic Developments

Frontiers in Pharmacology, Journal Year: 2017, Volume and Issue: 8

Published: Sept. 25, 2017

Purinergic signalling, i.e. the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept not well accepted until early 1990's when receptor subtypes for purines and pyrimidines were cloned characterised, which includes 4 P1 (adenosine) receptor, 7 P2X ion channel receptors 8 P2Y G protein-coupled receptor. Early studies largely concerned with physiology, pharmacology biochemistry purinergic signalling. More recently, focus has been on pathophysiology therapeutic potential. There recognition use agonists treatment supraventicular tachycardia A2A antagonists are promising Parkinson's disease. Clopidogrel, a P2Y¬12 antagonist, is widely used thrombosis stroke, blocking receptor-mediated platelet aggregation. Diquafasol, long acting P2Y¬2 agonist, being dry eye. P2X3 have developed that orally bioavailable stable vivo currently clinical trials chronic cough, bladder incontinence, visceral pain hypertension. Antagonists to P2X7 investigated inflammatory disorders, including neurodegenerative diseases. Other investigations progress agents osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes cancer.

Language: Английский

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Cortical Potentiation in Chronic Neuropathic Pain and the Future Treatment

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 363 - 363

Published: March 4, 2025

Pain, or the ability to feel pain and express unpleasantness caused by peripheral injuries, are functions of central nervous system. From sensory nerve terminals certain cortical regions brain, activation related neural networks underlies process. Recently, our knowledge has been increasing dramatically, due advancement scientific approaches. We no longer see brain as a random matrix for but, rather, we able identify step-by-step selective signaling proteins, neurons, that preferentially contribute process chronic its negative emotions, like anxiety fear. However, there is still lacking effective drugs methods treatment clinically. While first-line acute mental diseases also applied clinical management pain, their prolonged usage always causes serious side effects. In this short review, will update summarize recent progress in field mainly focus on roles synaptic mechanisms neuropathic pain. Furthermore, potential drug targets (such plasticity-related molecules, ionic channels, cytokines, neuropeptides) be discussed well. hope review can provide new, valuable insight into

Language: Английский

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A new perspective on the anterior cingulate cortex and affective pain

Neuroscience & Biobehavioral Reviews, Journal Year: 2018, Volume and Issue: 90, P. 200 - 211

Published: April 24, 2018

Language: Английский

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The Medial Prefrontal Cortex as a Central Hub for Mental Comorbidities Associated with Chronic Pain

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(10), P. 3440 - 3440

Published: May 13, 2020

Chronic pain patients frequently develop and suffer from mental comorbidities such as depressive mood, impaired cognition, other significant constraints of daily life, which can only insufficiently be overcome by medication. The emotional cognitive components are processed the medial prefrontal cortex, comprises anterior cingulate prelimbic, infralimbic cortex. All three subregions significantly affected chronic pain: magnetic resonance imaging has revealed gray matter loss in all these areas conditions. While cortex appears hyperactive, regions show reduced activity. receives ascending, nociceptive input, but also exerts important top-down control sensation: its projections main cortical input periaqueductal gray, is part descending inhibitory system at spinal level. A multitude neurotransmitter systems contributes to fine-tuning local circuitry, cholinergic GABAergic signaling particularly emerging relevant affective processing within Accordingly, factors distraction, positive anticipation relief placebo ameliorate affecting mPFC function, making this area a promising target region for medical well psychosocial interventions therapy.

Language: Английский

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Anti-inflammatory protein TSG-6 secreted by bone marrow mesenchymal stem cells attenuates neuropathic pain by inhibiting the TLR2/MyD88/NF-κB signaling pathway in spinal microglia

Journal of Neuroinflammation, Journal Year: 2020, Volume and Issue: 17(1)

Published: May 11, 2020

Abstract Background Neuroinflammation plays a vital role in the development and maintenance of neuropathic pain. Recent evidence has proved that bone marrow mesenchymal stem cells (BMSCs) can inhibit pain possess potent immunomodulatory immunosuppressive properties via secreting variety bioactive molecules, such as TNF-α-stimulated gene 6 protein (TSG-6). However, it is unknown whether BMSCs exert their analgesic effect against by TSG-6. Therefore, present study aimed to evaluate effects TSG-6 released from on induced chronic constriction injury (CCI) rats explored possible underlying mechanisms vitro vivo. Methods were isolated rat characterized flow cytometry functional differentiation. One day after CCI surgery, about 5 × 10 intrathecally injected into spinal cerebrospinal fluid. Behavioral tests, including mechanical allodynia, thermal hyperalgesia, motor function, carried out at 1, 3, 5, 7, 14 days surgery. Spinal cords processed for immunohistochemical analysis microglial marker Iba-1. The mRNA levels pro-inflammatory cytokines (IL-1β, TNFα, IL-6) detected real-time RT-PCR ELISA. activation TLR2/MyD88/NF-κB signaling pathway was evaluated Western blot immunofluorescence staining. exogenous recombinant CCI-induced allodynia heat hyperalgesia observed behavioral tests. In experiments, primary cultured microglia stimulated with TLR2 agonist Pam3CSK4, then co-cultured or expression TLR2, MyD88, p-p65 blot. IL-1β, IL-6 transfected TSG-6-specific shRNA fluid vivo Pam3CSK4-treated investigate participated therapeutic neuroinflammation. Results We found ameliorated intrathecal injection BMSCs. Moreover, administration inhibited neuroinflammation cord tissues. anti-inflammatory property attenuated when silenced. also ipsilateral dorsal horn Meanwhile, we effectively Furthermore, experiments showed downregulated reduced production cytokines, IL-6, TNF-α, treated specific Pam3CSK4. Conclusions demonstrated paracrine mechanism which targets elicit neuroprotection sustained relief secretion.

Language: Английский

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Different exercise modalities relieve pain syndrome in patients with knee osteoarthritis and modulate the dorsolateral prefrontal cortex: A multiple mode MRI study

Brain Behavior and Immunity, Journal Year: 2019, Volume and Issue: 82, P. 253 - 263

Published: Aug. 28, 2019

Language: Английский

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Current Understanding of the Neural Circuitry in the Comorbidity of Chronic Pain and Anxiety

Neural Plasticity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 13

Published: Feb. 15, 2022

Chronic pain patients often develop mental disorders, and anxiety disorders are common. We hypothesize that the comorbid results from an imbalance between reward antireward system due to persistent pain, which leads dysfunction of regulatory system. In this review, we will focus on changes in neuroplasticity, especially neural circuits, during chronic as observed animal studies. Several circuits within specific regions brain, including nucleus accumbens, lateral habenular, parabrachial nucleus, medial septum, anterior cingulate cortex, amygdala, hippocampus, prefrontal bed stria terminalis, be discussed based novel findings after chemogenetic or optogenetic manipulation. believe these studies provide insights into human conditions can guide clinical practice.

Language: Английский

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Therapeutic Efficacy of Intranasal N-Acetyl-L-Cysteine with Cell-Penetrating Peptide-Modified Polymer Micelles on Neuropathic Pain in Partial Sciatic Nerve Ligation Mice

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 44 - 44

Published: Jan. 1, 2025

Background/Objectives: We previously demonstrated that the intranasal administration of cell-penetrating Tat peptide-modified carrier, PEG-PCL-Tat, improves drug delivery to central nervous system. This study aimed evaluate potential post-onset N-acetyl-L-cysteine (NAC) combined with PEG-PCL-Tat (NAC/PPT) for neuropathic pain. Methods: Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) in mice. Mechanical allodynia assessed using von Frey test on days 11–14 post-ligation. NAC or NAC/PPT intranasally administered after onset. Western blotting and immunohistochemistry were conducted ionized calcium-binding adapter molecule 1 (Iba-1) expression microglial activation spinal cord. Results: exacerbated 11 PSNL The alone prevented exacerbation but failed provide a therapeutic effect against In contrast, ameliorated PSNL-induced tactile allodynia, maximum efficacy seen 13 14 ligation. Iba-1 levels tended increase mice compared controls. trend increased attenuated NAC/PPT, not alone. Immunohistochemistry revealed an number Iba-1-stained microglia ipsilateral cord mice, which significantly suppressed NAC/PPT. Conclusions: These results suggest ameliorates mechanical suppressing induction might be useful tool pharmacological management

Language: Английский

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Acute and Chronic Pain Processing in the Thalamocortical System of Humans and Animal Models

Neuroscience, Journal Year: 2017, Volume and Issue: 387, P. 58 - 71

Published: Oct. 1, 2017

Language: Английский

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