Long-term pain, neuroinflammation and glial activation

2010 ◽  
Vol 1 (2) ◽  
pp. 67-72 ◽  
Author(s):  
Elisabeth Hansson
Keyword(s):  
Endothelial Cells ◽  
Glial Cells ◽  
Neuronal Excitability ◽  
The Body ◽  
Low Grade ◽  
Pathological State ◽  
Pain Sensation ◽  
Capillary Endothelial Cells ◽  
Low Grade Inflammation

AbstractNociceptive and neuropathic pain signals are known to result from noxious stimuli, which are converted into electrical impulses within tissue nociceptors. There is a complex equilibrium of pain-signalling and pain-relieving pathways connecting PNS and CNS. Drugs against long-term pain are today directed against increased neuronal excitability, mostly with less success.An injury often starts with acute physiological pain, which becomes inflammatory, nociceptive, or neuropathic, and may be transferred into long-term pain. Recently a low-grade inflammation was identified in the spinal cord and along the pain pathways to thalamus and the parietal cortex. This neuroinflammation is due to activation of glial cells, especially microglia, with production of cytokines and other inflammatory mediators within the CNS. Additionally, substances released to the blood from the injured region influence the blood–brain barrier, and give rise to an increased permeability of the tight junctions of the capillary endothelial cells, leading to passage of blood cells into the CNS. These cells are transformed into reactive microglia. If the inflammation turns into a pathological state the astrocytes will be activated. They are coupled into networks and respond to substances released by the capillary endothelial cells, to cytokines released from microglia, and to neurotransmitters and peptides released from neurons. As the astrocytes occupy a strategic position between the vasculature and synapses, they monitor the neuronal activity and transmitter release. Increased release of glutamate and ATP leads to disturbances in Ca2+ signalling, increased production of cytokines and free radicals, attenuation of the astrocyte glutamate transport capacity, and conformational changes in the astrocytic cytoskeleton, the actin filaments, which can lead to formation and rebuilding of new synapses. New neuronal contacts are established for maintaining and spreading pain sensation with the astrocytic networks as bridges. Thereby the glial cells can maintain the pain sensation even after the original injury has healed, and convert the pain into long-term by altering neuronal excitability. It can even be experienced from other parts of the body. As astrocytes are intimate co-players with neurons in the CNS, more knowledge on astrocyte responses to inflammatory activators may give new insight in our understanding of mechanisms of low-grade inflammation underlying long-term pain states and pain spreading. Novel treatment strategies would be to restore glial cell function and thereby attenuate the neuroinflammation.

scholarly journals Effect Long-Term Exposure to Different Doses of Lipopolysaccharides on the Intestinal Mucosal Immune Barrier

2019 ◽  
Author(s):  
Chao Li ◽  
Baoyu Zhao ◽  
Chenchen Wu
Keyword(s):  
Layer Thickness ◽  
Goblet Cells ◽  
The Body ◽  
Low Grade ◽  
Low Doses ◽  
Mucus Layer ◽  
High Doses ◽  
Low Grade Inflammation ◽  
Different Doses

The small intestinal villus is covered with a thick layer of mucus that is secreted by goblet cells and functions primarily to first barrier from damage by toxic substance. Recent studies showed that goblet cells and mucins involved in complex immune function. Lipopolysaccharide (LPS) is widespread in the housing of livestock, which can induce bacterial infection symptoms and immunological stress within a short of time. Therefore, we aimed to study the effects of long-term exposure to different doses of LPS on intestinal mucus layer and immune barrier. The result showed that mucus layer thickness and goblet cell functions were significantly increased after low doses of LPS. The intestinal mucosal barrier can block the bacteria of the lumen, but LPS can penetrate this barrier into the blood, putting the body in a state of chronic low-grade inflammation and reducing the body’s immune function. However, after long-term exposure to high doses of LPS, a large number of lysosomes in goblet cells caused loss of function, and mucus layer thickness was significantly decreased. A large amount of LPS stuck to the mucus, leading to normal LPS and inflammatory cytokines level of plasma. The intestinal tissue morphology was damaged, and a number of immune cells were necrosis in the intestine. Collectively, long-term exposure to low doses of LPS lead to chronic low-grade inflammation in the body. Long-term exposure to high doses of LPS can be directly linked to the severity of the immunosuppression in the body.

scholarly journals Dietary Fiber's Effect on High Sensitivity C-reactive Protein Serum in Sedentary Workers

2021 ◽  
Vol 5 (1) ◽  
pp. 40
Author(s):  
Livia Kurniati Saputra ◽  
Dian Novita Chandra ◽  
Ninik Mudjihartini
Keyword(s):  
Body Weight ◽  
High Sensitivity ◽  
The Body ◽  
Low Grade ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Dietary Fiber Intake ◽  
Anti Inflammatory ◽  
Low Grade Inflammation ◽  
Inflammatory Effect

Low grade inflammation has been recognized of being involved in the pathogenesis of chronic disease pandemic. Individual lifestyle plays a major role in the development of low grade inflammation. Sedentary workers are at risk of low grade inflammation due to the nature of their work. Dietary habit also contributes to inflammatory status in the body. Dietary fiber intake indirectly affects the immune system. It has been hypothesized that fiber has anti-inflammatory effects, both body weight-related and body weight-unrelated This review will focus more on body weight-unrelated anti-inflammatory effect of fiber, especially through fiber’s fermentation metabolites, the short chain fatty acid (SCFA). Its anti-inflammatory effect can be seen by monitoring a biomarker of inflammation in the body, the high sensitivity C-reactive protein (hsCRP). This review’s objective is to cover the mechanisms and role of dietary fiber intake on serum hsCRP level as a marker of low grade inflammation on sedentary workers. 

scholarly journals Selenium and Inflammation— Potential Use and Future Perspectives

2015 ◽  
Vol 11 (02) ◽  
pp. 97 ◽  
Author(s):  
Leonidas H Duntas ◽  
Alicja Hubalewska-Dydejczyk ◽  
◽  
Keyword(s):  
Trace Element ◽  
Thioredoxin Reductase ◽  
The Body ◽  
Low Grade ◽  
Toll Like Receptor ◽  
Future Perspectives ◽  
Low Grade Inflammation ◽  
Light Chain Enhancer ◽  
Potential Use ◽  
Se Status

The essential trace element selenium (Se) is constitutively incorporated as selenocysteine, in proteins, among others in antioxidative selenoproteins, such as glutathione peroxidase(s) and thioredoxin reductase. Since chronic inflammation is thought to deplete Se stores in the body, Se supplementation should be considered in prolonged inflammatory states, Se being the trace element the most affected in chronic or low-grade inflammation. Se administration might also be beneficial in bacterial and viral diseases as well as metabolic and autoimmune diseases. In order to maintain a Se steady state, or “selenostasis,” Se supplementation, via either diet or compounds, is required to preserve the activity of selenoproteins in antioxidative and redox processes. Importantly, Se could play a pivotal role in the maintenance of homeostasis in infected tissues by inhibiting the proinflammatory toll-like receptor nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway and counteracting proinflammatory cytokine action. Finally, while Se status shows considerable promise as a valid marker of inflammatory and autoimmune disease, new functional Se nanoparticles and highly bioavailable selenomethionine compounds will in all probability provide a more efficacious and reliable intervention tool in both preventive and therapeutic disease management.

scholarly journals Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
◽  
Heli Julkunen ◽  
Anna Cichońska ◽  
P Eline Slagboom ◽  
Peter Würtz
Keyword(s):  
General Population ◽  
Disease Onset ◽  
Severe Pneumonia ◽  
Blood Sampling ◽  
Low Grade ◽  
Healthy Individuals ◽  
Metabolic Biomarkers ◽  
Low Grade Inflammation ◽  
Increased Susceptibility

Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007–2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7–11 years after blood sampling (2.6 [1.7–3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1–15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population.

scholarly journals Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-Albuminuric Diabetic Kidney Disease

2020 ◽  
Vol 9 (9) ◽  
pp. 3006
Author(s):  
Vadim V. Klimontov ◽  
Anton I. Korbut ◽  
Nikolai B. Orlov ◽  
Maksim V. Dashkin ◽  
Vladimir I. Konenkov
Keyword(s):  
Growth Factors ◽  
Kidney Disease ◽  
Low Grade ◽  
Hs Crp ◽  
Low Grade Inflammation ◽  
Egfr Decline ◽  
Multiplex Bead ◽  
Circulating Cytokines

A panel of cytokines and growth factors, mediating low-grade inflammation and fibrosis, was assessed in patients with type 2 diabetes (T2D) and different patterns of chronic kidney disease (CKD). Patients with long-term T2D (N = 130) were classified into four groups: no signs of CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 without albuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m2; albuminuria and eGFR <60 mL/min/1.73 m2. Thirty healthy subjects were acted as control. Twenty-seven cytokines and growth factors were assessed in serum by multiplex bead array assay. Serum hs-CRP, urinary nephrin, podocine, and WFDC2 were measured by ELISA. Patients with T2D showed elevated IL-1Ra, IL-6, IL-17A, G-CSF, IP-10, MIP-1α, and bFGF levels; concentrations of IL-4, IL-12, IL-15, INF-γ, and VEGF were decreased. IL-6, IL-17A, G-CSF, MIP-1α, and bFGF correlated negatively with eGFR; IL-10 and VEGF demonstrated negative associations with WFDC2; no relationships with podocyte markers were found. Adjusted IL-17A and MIP-1α were predictors of non-albuminuric CKD, IL-13 predicted albuminuria with preserved renal function, meanwhile, IL-6 and hsCRP were predictors of albuminuria with eGFR decline. Therefore, albuminuric and non-albuminuric CKD in T2D patients are associated with different pro-inflammatory shifts in the panel of circulating cytokines.

scholarly journals Serum Calprotectin and Chemerin Concentrations as Markers of Low-Grade Inflammation in Prepubertal Children with Obesity

2020 ◽  
Vol 17 (20) ◽  
pp. 7575 ◽  
Author(s):  
Grażyna Rowicka ◽  
Hanna Dyląg ◽  
Magdalena Chełchowska ◽  
Halina Weker ◽  
Jadwiga Ambroszkiewicz
Keyword(s):  
Low Grade ◽  
Serum Concentrations ◽  
C Reactive Protein ◽  
Prepubertal Children ◽  
Reactive Protein ◽  
Study Population ◽  
Normal Body Weight ◽  
Wbc Count ◽  
Low Grade Inflammation

In adults, obesity is associated with chronic low-grade inflammation, which may cause long-term adverse health consequences. We evaluated whether obesity in prepubertal children also generates this kind of inflammation and whether calprotectin and chemerin may be useful markers for early detection of such inflammation in this group of children. The study population included 83 children aged 2 to 10 years; 62 with obesity and without components of metabolic syndrome and 21 healthy controls with normal body weight. White blood cell (WBC) count, concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), calprotectin, and chemerin were determined in peripheral blood. Our study showed that in the group with obesity, serum concentrations of calprotectin and chemerin, as well as CRP were significantly higher as compared with the controls. We found a significant positive correlation between serum chemerin concentrations and BMI z-score (r = 0.33, p < 0.01) in children with obesity. Chemerin concentration was also positively correlated with CRP level (r = 0.36, p < 0.01) in the whole group of children. These findings suggest that obesity may generate chronic low-grade inflammation as early as in the prepubertal period which can be indicated by significantly higher serum concentrations of calprotectin and chemerin. Calprotectin and especially chemerin seem to be promising indicators of this type of inflammation in children with obesity, but the correlation between these markers requires further research.

scholarly journals TRPV1 Responses in the Cerebellum Lobules V, VIa and VII Using Electroacupuncture Treatment for Inflammatory Hyperalgesia in Murine Model

2020 ◽  
Vol 21 (9) ◽  
pp. 3312 ◽  
Author(s):  
Chanya Inprasit ◽  
Yi-Wen Lin
Keyword(s):  
Inflammatory Pain ◽  
The Body ◽  
Pain Sensation ◽  
Inflammatory Hyperalgesia ◽  
Protein Levels ◽  
Important Symptom ◽  
Zusanli Acupoint ◽  
Transient Receptor ◽  
Electroacupuncture Treatment

Inflammatory pain sensation is an important symptom which protects the body against additional tissue damage and promotes healing. Discovering long-term and effective treatments for pain remains crucial in providing efficient healthcare. Electroacupuncture (EA) is a successful therapy used for pain relief. We aimed to investigate effects and mechanisms of Complete Freund’s Adjuvant (CFA)-inducing inflammatory pain in the cerebellum, and the inhibition of this inflammatory hyperalgesia using EA at Zusanli acupoint (ST36). The results display a significant increase in mechanical and thermal sensitivities in the CFA and CFA + SHAM groups, which was significantly reduced in the CFA+EA and CFA + KO groups. This evidence was substantiated in the protein levels observed using immunoblotting, and presented with significant escalations after CFA inducing inflammatory hyperalgesia in CFA and CFA + SHAM groups. Then, they were significantly attenuated by EA in the CFA + EA group. Furthermore, the CFA + transient receptor vanilloid member 1 (TRPV1)−/− group indicated similar significant decreases of protein expression. Additionally, a concomitant overexpression in lobule VIa was also observed in immunofluorescence. These consequences suggest that CFA-induced inflammatory pain provokes modifications in cerebellum lobules V, VIa and VII, which can subsequently be regulated by EA treatment at the ST36 through its action on TRPV1 and related molecular pathways.

scholarly journals Increased Serum and Musculotendinous Fibrogenic Proteins following Persistent Low-Grade Inflammation in a Rat Model of Long-Term Upper Extremity Overuse

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71875 ◽  
Author(s):  
Helen G. L. Gao ◽  
Paul W. Fisher ◽  
Alex G. Lambi ◽  
Christine K. Wade ◽  
Ann E. Barr-Gillespie ◽  
...  
Keyword(s):  
Upper Extremity ◽  
Rat Model ◽  
Low Grade ◽  
Low Grade Inflammation

scholarly journals Osteopontin: The Molecular Bridge between Fat and Cardiac–Renal Disorders

2020 ◽  
Vol 21 (15) ◽  
pp. 5568
Author(s):  
Elena Vianello ◽  
Marta Kalousová ◽  
Elena Dozio ◽  
Lorenza Tacchini ◽  
Tomáš Zima ◽  
...  
Keyword(s):  
Molecular Interactions ◽  
Visceral Fat ◽  
Current Knowledge ◽  
Common Factor ◽  
Cell Types ◽  
The Body ◽  
Matricellular Protein ◽  
Low Grade ◽  
Renal Disorders ◽  
Low Grade Inflammation

Osteopontin (OPN) is a multifaceted matricellular protein, with well-recognized roles in both the physiological and pathological processes in the body. OPN is expressed in the main organs and cell types, in which it induces different biological actions. During physiological conditioning, OPN acts as both an intracellular protein and soluble excreted cytokine, regulating tissue remodeling and immune-infiltrate in adipose tissue the heart and the kidney. In contrast, the increased expression of OPN has been correlated with the severity of the cardiovascular and renal outcomes associated with obesity. Indeed, OPN expression is at the “cross roads” of visceral fat extension, cardiovascular diseases (CVDs) and renal disorders, in which OPN orchestrates the molecular interactions, leading to chronic low-grade inflammation. The common factor associated with OPN overexpression in adipose, cardiac and renal tissues seems attributable to the concomitant increase in visceral fat size and the increase in infiltrated OPN+ macrophages. This review underlines the current knowledge on the molecular interactions between obesity and the cardiac–renal disorders ruled by OPN.

Sign in / Sign up

Export Citation Format

Share Document