Cerebrospinal Fluid Glutamate Levels in Chronic Migraine

Cephalalgia ◽  
2004 ◽  
Vol 24 (9) ◽  
pp. 735-739 ◽  
Author(s):  
MFP Peres ◽  
E Zukerman ◽  
CA Senne Soares ◽  
EO Alonso ◽  
BFC Santos ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Chronic Migraine ◽  
Glutamate Receptors ◽  
Pain Score ◽  
Clinical Data ◽  
Central Sensitization ◽  
Tender Points ◽  
Data Link ◽  
Headache Intensity ◽  
Sensitization Process

Both preclinical and clinical data link glutamate to the migraine pathophisiology. Altered plasma, platelets and cerebrospinal (CSF) glutamate levels have been reported in migraine patients. Chronic migraine is comorbid with several conditions. It has been recently shown chronic migraine comorbidity with fibromyalgia. The objective of this study was to study cerebrospinal fluid glutamate levels in chronic migraine patients with and without fibromyalgia. We studied 20 chronic migraine patients, with and without fibromyalgia, compared to age-sex matched controls. CSF glutamate levels were measured by HPLC. CSF glutamate demonstrated significantly higher levels in patients with fibromyalgia compared to those without fibromyalgia. Patients overall had higher CSF glutamate levels than controls. Mean pain score correlated with glutamate levels in chornic migraine patients. Tender points, the hallmark of fibromyalgia, can be considered as pressure allodynia, and is probably mediated by central sensitization, with increase in CSF glutamate levels. We postulate chronic migraine patients with fibromyalgia, in addition to have more disabling headaches, suffer from a more severe central sensitization process. This subtype of patients may respond to medications modulating glutamate receptors. Headache intensity correlate with glutamate levels in chronic migraine patients.

Cerebrospinal fluid microscopy as an index for predicting the prognosis of cryptococcal meningitis patients with and without HIV

2020 ◽  
Vol 15 (17) ◽  
pp. 1645-1652
Author(s):  
Keming Zhang ◽  
Hang Li ◽  
Lei Zhang ◽  
Wanqing Liao ◽  
Liyan Ling ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Data ◽  
Cryptococcal Meningitis ◽  
Fungal Burden ◽  
Hospital Patients ◽  
Patient Prognosis ◽  
Worse Prognosis ◽  
Fluid Test

Aim: To evaluate the clinical data and quantitative cerebrospinal fluid for associations with the outcome of cryptococcal meningitis (CM) patients in the hospital. Patients & methods: We retrospectively analyzed a total of 139 CM patients comprising 108 without HIV and 31 with HIV admitted in a Jiang Xi hospital. Resμlts: We found that CM patients with the high fungal burden (≥10 yeasts/μl) (26.3%) had a worse prognosis than those with the low fungal burden (<10 yeasts/μl). (4.9%) (p = 0.0007 <0.05). Conclusion: In CM patients, a fungal burden of 10 yeasts/μl in the first cerebrospinal fluid test may be used as an indicator of patient prognosis, and we can personalize patients’ treatment based on the fungal burden to improve prognosis.

Cerebrospinal fluid of chronic osteoarthritic patients induced interleukin-6 release in human glial cell-line T98G

2020 ◽  
Author(s):  
Weiling Liu ◽  
Chunmei Li ◽  
Francis Chee Kuan Tan ◽  
Hong Jye Neo ◽  
Yiong Huak Chan ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Cerebrospinal Fluid ◽  
Cell Line ◽  
Pain Score ◽  
Western Blotting ◽  
Interleukin 6 ◽  
Antibody Array ◽  
T98g Cell ◽  
Cell Lysate ◽  
Tnf Α

Abstract Background Chronic osteoarthritic pain is not well understood in terms of its pathophysiological mechanism. Activated glial cells are thought to play a role in the maintenance of chronic pain. T98G glioblastoma cell line was previously observed to release higher amounts of interleukin-6 (IL-6) when treated with cerebrospinal fluid (CSF) from patients with another chronic pain condition, post-herpetic neuralgia. In this study, we investigated the ability of CSF from patients diagnosed with knee osteoarthritis suffering from chronic pain, to trigger the release of pro-inflammatory cytokines, IL-6, IL-1beta and tumour necrosis factor alpha (TNF-α) from T98G. Characterization of upstream signalling was also explored. Methods 15 osteoarthritis patients undergoing total knee replacement due to chronic knee pain and 15 patients without pain undergoing other surgeries with spinal anaesthesia were prospectively recruited. CSF was collected during anaesthesia. CSF were added to cultured T98G cells in the presence of lipopolysaccharide. IL-6, IL-1β and TNF-α release from T98G cells were measured using enzyme immunoassay. Antibody array and western blotting were performed using CSF-triggered T98G cell lysates to identify possible signalling targets. Age, gender and pain scores were recorded. Mann-Whitney U test was used to compare IL-6 release and protein expression between groups. Association between IL-6 and pain score was analysed using linear regression. Results Significant higher levels of IL-6 were released by T98G cells when induced by osteoarthritis patients' CSF in presence of lipopolysaccharide. IL-6 levels showed positive association with pain score (adjusted B estimate= 10.1 (95% Confidence Interval 4.3-15.9); p= 0.001). Antibody array conducted with 6 pooled T98G cell lysate induced with osteoarthritis pain patient CSF identified greater than 2-fold proteins including STE20-related kinase adaptor protein and spleen tyrosine kinase. Further validation done using western blotting of individual CSF-triggered T98G cell lysate showed non-significant increase. Conclusion Higher IL-6 release from T98G when triggered by OA CSF, in the presence of lipopolysaccharide, suggest presence of "unknown molecule" in CSF that may be crucial in the maintenance phase of chronic pain in our osteoarthritis population. Further studies on the signalling pathways involved in pain and relevance of IL-6 release from T98G in other pain models are needed.

Groups II and III Metabotropic Glutamate Receptors Differentially Modulate Brief and Prolonged Nociception in Primate STT Cells

2000 ◽  
Vol 84 (6) ◽  
pp. 2998-3009 ◽  
Author(s):  
Volker Neugebauer ◽  
Ping-Sun Chen ◽  
William D. Willis
Keyword(s):  
Glutamate Receptors ◽  
Dorsal Horn ◽  
Central Sensitization ◽  
Metabotropic Glutamate Receptors ◽  
Background Activity ◽  
Mechanical Stimuli ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii

The heterogeneous family of G-protein-coupled metabotropic glutamate receptors (mGluRs) provides excitatory and inhibitory controls of synaptic transmission and neuronal excitability in the nervous system. Eight mGluR subtypes have been cloned and are classified in three subgroups. Group I mGluRs can stimulate phosphoinositide hydrolysis and activate protein kinase C whereas group II (mGluR2 and 3) and group III (mGluR4, 6, 7, and 8) mGluRs share the ability to inhibit cAMP formation. The present study examined the roles of groups II and III mGluRs in the processing of brief nociceptive information and capsaicin-induced central sensitization of primate spinothalamic tract (STT) cells in vivo. In 11 anesthetized male monkeys ( Macaca fascicularis), extracellular recordings were made from 21 STT cells in the lumbar dorsal horn. Responses to brief (15 s) cutaneous stimuli of innocuous (brush), marginally and distinctly noxious (press and pinch, respectively) intensity were recorded before, during, and after the infusion of group II and group III mGluR agonists into the dorsal horn by microdialysis. Different concentrations were applied for at least 20 min each (at 5 μl/min) to obtain cumulative concentration-response relationships. Values in this paper refer to the drug concentrations in the microdialysis fibers; actual concentrations in the tissue are about three orders of magnitude lower. The agonists were also applied at 10–25 min after intradermal capsaicin injection. The group II agonists (2S,1′S,2′S)-2-(carboxycyclopropyl)glycine (LCCG1, 1 μM-10 mM, n = 6) and (−)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268; 1 μM-10 mM, n = 6) had no significant effects on the responses to brief cutaneous mechanical stimuli (brush, press, pinch) or on ongoing background activity. In contrast, the group III agonist L(+)-2-amino-4-phosphonobutyric acid (LAP4, 0.1 μM-10 mM, n = 6) inhibited the responses to cutaneous mechanical stimuli in a concentration-dependent manner, having a stronger effect on brush responses than on responses to press and pinch. LAP4 did not change background discharges significantly. Intradermal injections of capsaicin increased ongoing background activity and sensitized the STT cells to cutaneous mechanical stimuli (ongoing activity > brush > press > pinch). When given as posttreatment, the group II agonists LCCG1 (100 μM, n = 5) and LY379268 (100 μM, n = 6) and the group III agonist LAP4 (100 μM, n = 6) reversed the capsaicin-induced sensitization. After washout of the agonists, the central sensitization resumed. Our data suggest that, while activation of both group II and group III mGluRs can reverse capsaicin-induced central sensitization, it is the actions of group II mGluRs in particular that undergo significant functional changes during central sensitization because they modulate responses of sensitized STT cells but have no effect under control conditions.

scholarly journals Effects of Botulinum Toxin on Migraine Attack Features in Chronic Migraine: A Six-Month Open-Label Observation Study through Electronic Diary Smartphone Application

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 668 ◽  
Author(s):  
Antonio Santoro ◽  
Marianna Delussi ◽  
Maurizio Leone ◽  
Anna Maria Miscio ◽  
Laura De Rocco ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Central Sensitization ◽  
Smartphone Application ◽  
Electronic Diary ◽  
Open Label ◽  
Observation Study ◽  
Nociceptive Transmission ◽  
Headache Diary ◽  
Application Data

OnobotulintoxinA (OBT-A) is a treatment option for Chronic Migraine (CM). It works on central sensitization and pain but its mode of action is still unknown. To observe how OBT-A treatment works on single migraine attacks, this paper covers an over-6-month observation period through self-reported smartphone application data. This was an observational, open-label cohort study conducted on 34 CM patients under OBT-A treatment, selected between December 2016 and December 2017, who agreed to download a smartphone headache diary application (Aid Diary) according to the study instructions. The analysis was conducted using the smartphone application data reports on allodynia, intensity and extension of pain, and vegetative symptoms. We analysed a total of 707 records of single migraine attacks reported by compliant users (n = 34) in real-time. OBT-A significantly reduced allodynia, the number of vegetative symptoms, pain extension and intensity in single migraine attacks. Pain intensity was correlated with pain extension. In single migraine attacks, OBT-A improved symptoms of central sensitization. This action could be exerted by modulating nociceptive transmission and reducing the burden of single migraine episodes and improving the overall quality of life.

scholarly journals NR2B-Tyr phosphorylation regulates synaptic plasticity in central sensitization in a chronic migraine rat model

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Xue-Ying Wang ◽  
Hui-Ru Zhou ◽  
Sha Wang ◽  
Chao-Yang Liu ◽  
Guang-Cheng Qin ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Chronic Migraine ◽  
Rat Model ◽  
Central Sensitization

scholarly journals P2X7R-mediated Autophagic Impairment Contributes to Central Sensitization in a chronic Migraine Model with Recurrent Nitroglycerin Stimulation in Mice

2020 ◽  
Author(s):  
Li Jiang ◽  
Yixin Zhang ◽  
Feng Jing ◽  
Ting Long ◽  
Guangcheng Qin ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Central Sensitization ◽  
Cellular Localization ◽  
Microglial Activation ◽  
Purinergic Receptor ◽  
Radiant Heat ◽  
Underlying Mechanism ◽  
Autophagic Flux ◽  
Pathophysiological Mechanism

Abstract Background: Central sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to the central sensitization. The P2X7 receptor (P2X7R) is a purinergic receptor expressed in microglia and participates in central sensitization in chronic pain, but its role in CM is unclear. Numerous studies have shown that P2X7R regulates the level of autophagy and that autophagy affects the microglial activation and inflammation. Recently, autophagy has been shown to be involved in neuropathic pain, but there is no information about autophagy in CM. Therefore, the current study investigated the role of P2X7R in CM and its underlying mechanism, focusing on autophagy regulation.Methods: The CM model was established by repeated intraperitoneal injection of nitroglycerin (NTG) in mice. A Von Frey filament and radiant heat were used to assess the mechanical and thermal hypersensitivity. Western blotting and immunofluorescence assays were performed to detect the expression of P2X7R, autophagy-related proteins, and the cellular localization of P2X7R. To determine the role of P2X7R and autophagy in CM, we detected the effects of the autophagy inducer, rapamycin (RAPA) and P2X7R antagonist, Brilliant Blue G (BBG), on pain behavior and the expression of calcitonin gene-related peptide (CGRP) and c-fos. In addition, the effect of RAPA and BBG on microglial activation and subsequent inflammation were investigated.Results: The expression of P2X7R was increased and was mainly colocalized with microglia in the TNC following recurrent NTG administration. The autophagic flux was blocked in CM, which was characterized by up-regulated LC3-II, and accumulated autophagy substrate protein, p62. RAPA significantly improved the basal rather than acute hyperalgesia. BBG alleviated both basal and acute hyperalgesia. BBG activated the level of autophagic flux. RAPA and BBG inhibited the activation of microglia, limited the inflammatory response, and reduced the expression of CGRP and c-fos. Conclusions: Our results demonstrate the dysfunction of the autophagic process in CM. Activated autophagy may have a preventive effect on migraine chronification. P2X7R contributes to central sensitization through mediating autophagy regulation and might become a potential target for CM.

scholarly journals Pain at Rest as a Predictive Factor of Chronic Pain Related to Central Sensitization in Patients With Hip Osteoarthritis

2020 ◽  
Author(s):  
Yoshihisa Ohashi ◽  
Kensuke Fukushima ◽  
Gen Inoue ◽  
Kentaro Uchida ◽  
Tomohisa Koyama ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Score ◽  
Predictive Factor ◽  
Central Sensitization ◽  
Hip Osteoarthritis ◽  
Clinical Results ◽  
Harris Hip Score ◽  
Knee Oa ◽  
The Mean ◽  
Pain At Rest

Abstract Background Central sensitization (CS) has been identified as a factor that induces chronic pain in patients with osteoarthritis (OA). Although there are some reports of CS in knee OA, studies on CS in hip OA are lacking. We aimed to evaluate chronic pain related to CS in patients with hip OA using the CS Inventory (CSI). Additionally, we aimed to clarify the characteristics of patients with pain related to CS. Methods A total of 100 patients scheduled to undergo total hip arthroplasty (THA) for hip OA were retrospectively reviewed. We investigated the CSI score as an assessment of the extent to which the patients had pain related to CS. Additionally, we assessed the relationships between the CSI score and clinical factors, including age, duration of pain, degree of pain at rest and on activity, by using the visual analogue scale (VAS) and the Harris Hip Score. Results The mean CSI score was 19.54 ± 11.25 points. Twenty-one percent of the patients with a score of ≥ 30 were diagnosed as having chronic pain related to CS. The CSI score correlated significantly only with the VAS pain score at rest (r = 0.348, P < 0.001). Fifteen patients were diagnosed with CS syndromes (CSSs) in the assessment of CSI Part B. The mean CSI score was significantly higher in patients diagnosed with CSSs (30.00 ± 12.50) than in patients without a CSS (17.70 ± 10.00; P < 0.001). Conclusion Twenty-one percent of the patients scheduled to undergo THA for hip OA were diagnosed with chronic pain related to CS, which might influence the clinical results after THA. As the VAS pain score at rest was significantly correlated with the CSI score, pain at rest might be a predictive factor of chronic pain related to CS in patients with hip OA.

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