Sensitization Research Articles

Burning Mouth Syndrome Underlying Factors: A Roadmap From a Network Perspective.

To investigate the relationship between biological, psychological, and social factors underlying Burning Mouth Syndrome (BMS). A case (n = 40) and control (n = 42) study containing 80 variables was examined using two network models based on regularized partial correlations (n = 82). The structure of the associative pathways with the BMS was revealed. Direct associations involved Gastrointestinal Alterations (0.23), Vitamin D Deficiency (0.29), Musculoskeletal Alterations (0.29), Symptom Severity Score 2 (SSS2) (0.22), Cortisol Variation (0.10), Interpersonal Sensitivity (0.04), Hostility (0.03). Global Severity Index, Symptom Severity Score 1, Psychoticism, Obsession-Compulsion, Depression, Anxiety, and Somatization were indirectly related. The SSS2 was the most influential on BMS accuracy. Gastrointestinal alterations andvitamin D deficiency show a significant influence on BMS while cortisol mediates in multiple associative pathways between musculoskeletal alterations, gastrointestinal alterations, vitamin D deficiency, non-restorative sleep, fatigue, and cognitive problems. In addition to anxiety and depression, psychoticism, interpersonal sensitivity, and hostility stand out as psychological factors that seem to be related to a lack of vitamin D. None of the factors studied seem to have a relevant predictive potential for BMS, except for nonspecific symptoms of central sensitization.

Nociplastic Pain in Endometriosis: A Scoping Review

Endometriosis is an inflammatory chronic condition associated with nociceptive, neuropathic, and nociplastic pain. Central sensitization (CS) is the primary nociplastic pain mechanism. However, there are currently no standardized methods for detecting CS or nociplastic pain. This review aims to identify available tools for characterizing CS/nociplastic pain in endometriosis-related chronic pelvic pain. Following the PRISMA-P protocol, MEDLINE, Embase, Scopus, and PsychINFO databases were searched on 23 April 2024, for the terms “endometriosis”, “central sensitization”, “nociplastic pain”, “widespread pain”, and “assessment tools”. Publications were selected if they mentioned tool(s) for detecting nociplastic pain or CS in endometriosis patients. Information was extracted on study demographics, assessment types, and the tools used for detection. Of the 379 citations retrieved, 30 papers met the inclusion criteria. When working to identify CS and nociplastic pain, fourteen studies exclusively used patient-reported questionnaires, six used quantitative sensory testing (QST), two used clinical assessments, and eight used multiple approaches combining patient-reported questionnaires and clinical assessment. This review illustrates the diversity of tools currently used to identify CS and nociplastic pain in endometriosis patients. Further research is needed to evaluate their validity and to standardize methods in order to improve the accuracy of nociplastic pain identification and guide treatment.

Effectiveness of a brief multicomponent intervention to improve physical activity level and functional capacity in fibromyalgia and chronic fatigue syndrome (Synchronize+)

IntroductionFibromyalgia (FM) and chronic fatigue syndrome (CFS) are complex central sensitization syndromes that represent an important public health problem. Low cardiorespiratory fitness and muscle function with habitual intolerance to efforts are common characteristics of FM and CFS. This study aimed to examine the effect of a brief multicomponent intervention based on physical activity (PA), nutrition, and chronobiology on movement behaviors (PA, sedentary and sleep time), muscle strength, and cardiorespiratory capacity.Methodsrandomized controlled trial was conducted in primary healthcare in Catalonia. A total of 143 individuals with FM or FM and CFS concomitantly (age 50.8, SD 8.1; 94.4% women) were randomly allocated to the intervention (IG, n = 69) or control (CG, n = 74) groups. The IG participated in a brief multicomponent (PA, nutrition, and chronobiology) group-based intervention (4 sessions, 3 h/session) while the CG received usual primary care practice. Primary outcome measure was PA measured by the REGICOR-Short Physical Activity Questionnaire. Secondary outcomes were sedentary (International Physical Activity Questionnaire) and sleep time (Pittsburgh Sleep Quality Index), upper- and lower-body muscle strength (handgrip and sit-to-stand test, respectively), and aerobic capacity (6-min walk test). Data were collected at baseline and 3 months post-intervention.ResultsThe IG showed positive differences at 3-month follow-up, with highly appreciably PA levels, less sedentary time, and significantly improved sleep time. Significant between-group differences were also observed at 3 months, with better health values in the IG: PA and sleep time (370.3 ± 307.0 vs. 195.9 ± 289.1 min/week and 6.1 ± 1.6 vs. 5.5 ± 1.8 h/night, respectively) and less sedentary time (266.2 ± 153.3 vs. 209.4 ± 199.9 min/day). The IG also showed higher upper limb strength and significant lower-body strength both between and within groups, as well as significantly improved cardiorespiratory capacity.ConclusionThe Synchronize + multicomponent program implemented at primary healthcare has shown short-term effectiveness in improving 24-h movement behaviors and health outcomes in individuals with FM, with or without CFS. This intervention may be a first step in educating and motivating people with FM and CFS to adopt an active lifestyle, leading to improved health. Long-term follow-up will determine whether the changes are maintained over time and their impact on quality of life and healthcare costs.

Direct Immunofluorescence in Oral Lichen Planus and Related Lesions: Sensitivity, Specificity, and Diagnostic Accuracy in a Single Diagnostic Center in Poland

Objectives: Our study aimed to establish the basic reliability parameters of direct immunofluorescence test results in patients with oral lichen planus. Methods: We conducted an evaluation of individual antibody classes in the DIF and ELISA (BP180 antigen), comparing these results with the classical histopathological (HP) examination in a group of patients treated within the standard healthcare in our clinic. Results: Among 66 participants with oral changes indicative of LP, only 50% received histopathological confirmation of the LP diagnosis. Among those with a DIF profile entirely typical for LP (C3+, F+), 57.1% had a positive HP result. Fibrinogen deposits were identified in 42.4% and 36.4% of individuals with positive HP results for F1 and F2, respectively; 78.8% of patients with negative HP and 57.6% with positive HP exhibited no fibrinogen deposits. Simultaneous positivity for F1 and F2 occurred in all cases where F1 was positive. HP confirmed positive DIF for C3 in 50% of cases. Fibrinogen deposits demonstrated the highest diagnostic accuracy (61%). Sensitivity and specificity for fibrinogen deposits were 36% and 42% for F1 and 79% and 82% for F2. The positive predictive values were 67% for F1 and 67% for F2, while the negative predictive values were 58% for F1 and 56% for F2. Overall diagnostic accuracy was reported at 61% for F1 and 59% for F2. Conclusions: Our data indicate the complementarity of HP and immunological test results and the necessity of using both methods together in cases of doubt.

Metformin attenuates central sensitization by regulating neuroinflammation through the TREM2-SYK signaling pathway in a mouse model of chronic migraine

BackgroundChronic migraine (CM) is a serious neurological disorder. Central sensitization is one of the important pathophysiological mechanisms underlying CM, and microglia-induced neuroinflammation conduces to central sensitization. Triggering receptor expressed on myeloid cells 2 (TREM2) is presented solely in microglia residing within the central nervous system and plays a key role in neuroinflammation. Metformin has been shown to regulate inflammatory responses and exert analgesic effects, but its relationship with CM remains unclear. In the study, we investigated whether metformin modulates TREM2 to improve central sensitization of CM and clarified the potential molecular mechanisms.MethodsA CM mouse model was induced by administration of nitroglycerin (NTG). Behavioral evaluations were conducted using von Frey filaments and hot plate experiments. Western blot and immunofluorescence techniques were employed to investigate the molecular mechanisms. Metformin and the SYK inhibitor R406 were administered to mice to assess their regulatory effects on neuroinflammation and central sensitization. To explore the role of TREM2-SYK in regulating neuroinflammation with metformin, a lentivirus encoding TREM2 was injected into the trigeminal nucleus caudalis (TNC). In vitro experiments were conducted to evaluate the regulation of TREM2-SYK by metformin, involving interventions with LPS, metformin, R406, siTREM2, and TREM2 plasmids.ResultsMetformin and R406 pretreatment can effectively improve hyperalgesia in CM mice. Both metformin and R406 significantly inhibit c-fos and CGRP expression in CM mice, effectively suppressing the activation of microglia and NLRP3 inflammasome induced by NTG. With the administration of NTG, TREM2 expression gradually increased in TNC microglia. Additionally, we observed that metformin significantly inhibits TREM2 and SYK expression in CM mice. Lv-TREM2 attenuated metformin-mediated anti-inflammatory responses. In vitro experiments, knockdown of TREM2 inhibited LPS-induced SYK pathway activation and alleviated inflammatory responses. After the sole overexpression of TREM2, the SYK signaling pathway is activated, resulting in the activation of the NLRP3 inflammasome and an increased expression of pro-inflammatory cytokines; nevertheless, this consequence can be reversed by R406. The overexpression of TREM2 attenuates the inhibition of SYK activity mediated by metformin, and this effect can be reversed by R406.ConclusionsOur findings suggest that metformin attenuates central sensitization in CM by regulating the activation of microglia and NLRP3 inflammasome through the TREM2-SYK pathway.Graphical

Electroencephalographic power ratio and peak frequency difference associate with central sensitization in chronic pain.

Central sensitization, or increased responsiveness of the central nervous system to sensory input, is present in many chronic pain patients. Clinically, it is detected through subjective, patient-reported measures. There is a need for reliable, direct measurements of neural response to controlled stimuli to quantify neuronal dysfunction in pain. The goal of this work is to investigate cortical activity, recorded via electroencephalogram (EEG), during objective and calibrated painful stimulation in chronic pain patients.&#xD;Approach. Chronic pain patients (N=8) and healthy controls (N=8) participated in this study. We recorded electroencephalography (EEG) at rest (baseline) and during evoked pain tasks, including thermal and mechanical stimuli. The evoked pain was applied following the quantitative sensory testing (QST) protocol, which is a research technique that applies objective, calibrated painful stimuli. &#xD;Main results. Peak alpha frequency at rest was significantly lower in chronic pain patients compared to healthy controls (p<0.0002), while EEG alpha/theta and alpha/beta power ratios at rest were higher in patients (p<0.0002). During thermal QST, these power ratios decreased in patients and increased in controls (p<0.0002 for both). During mechanical QST, power ratios decreased or did not change. Furthermore, the peak theta-beta frequency difference at baseline was significantly lower in patients compared to controls (p<0.0002). During thermal QST, this difference increased in patients and decreased in controls; during mechanical QST, this difference increased in both patients and controls (p<0.0002). Functional connectivity analysis showed that controls had greater baseline theta connectivity strength that increased during mechanical QST (p<0.0002).&#xD;Significance. This work demonstrates differential patterns of EEG activity at rest and during acute painful stimulation in chronic pain patients compared to healthy controls. These measures may quantify an individual's tendency to experience chronic pain and central sensitization and serve as diagnostic biomarkers.

Pain characteristics in patients with hip osteoarthritis

PurposeExacerbations of osteoarthritis (OA) pain significantly impair activities of daily living and walking, thereby reducing quality of life. Despite various treatments, persistent pain remains a challenge, particularly in patients with hip OA, where pain perception mechanisms extend beyond nociceptive pain. This study examined the pain characteristics in patients with hip OA, with an emphasis on neuropathic pain and central sensitization (CS). MethodsA total of 421 patients scheduled for unilateral total hip arthroplasty were analyzed using the painDETECT score and Central Sensitization Inventory to classify the pain types as nociceptive (Noc), CS, neuropathic (Neu), or neuropathic with CS (NeuCS). ResultsThe results indicated that 72.9% of patients experienced Noc pain, while 5.0% experienced combined NeuCS pain. The Neu and NeuCS groups exhibited significantly lower modified Harris Hip Score and EuroQol-5 Dimensions Questionnaire (EQ-5D) scores than the Noc group, indicating worse clinical outcomes and quality of life. Neu pain was more intense at rest, and when combined with CS it significantly diminished the quality of life. ConclusionThese findings highlight the need for mechanism-based pain treatment strategies, such as Neu pain and CS components, which independently and cumulatively affect clinical scores and quality of life. This study highlights the importance of early recognition and targeted treatment of these pain mechanisms in patients with hip OA. Future research should focus on evaluating therapeutic interventions for Neu pain and CS to optimize patient outcomes.

Cross-Cultural Adaptation and Validation of the Central Sensitization Inventory Among Chinese Patients with Chronic Non-Specific Low Back Pain.

This research aims to develop and validate the Chinese version of the Central Sensitization Inventory (CSI-CV) for patients suffering from chronic non-specific low back pain (CNSLBP). The study evaluates both the validity and reliability of the CSI-CV. The cross-cultural adaptation of the scale strictly adhered to the principles of Bombardier and Beaton. Initially, two professors of Chinese-English translation independently translated the original CSI scale into the target language, and then collaborated with an expert in cross-cultural adaptation to merge into a single version. This version was back-translated into English by two professors whose native language is English. Following this, the scale underwent preliminary review by bilingual experts and the research team, and was preliminarily tested, ultimately culminating in the formation of the CSI-CV version. A total of 310 patients with CNSLBP completed the CSI-CV, while 50 of them repeated the survey one week later to test the stability of the scale. The CSI-CV's reliability, validity, and internal consistency were assessed through exploratory factor analysis (EFA), correlation coefficients, and Cronbach's α. EFA revealed five distinct factors from the 25 CSI-CV items, covering physical symptoms, emotional distress, fatigue and sleep disturbances, headaches and jaw symptoms, and urinary issues, with a total explained variance of 60.24%. The Cronbach's α was 0.910, and the intraclass correlation coefficient (ICC) was 0.924, indicating strong reliability. Moderate correlations were observed between CSI-CV scores and Five-Level EuroQol Five-Dimensional Questionnaire (r = -0.515), the Brief Pain Inventory (r = 0.586) and Oswestry Disability Index (r = 0.416), demonstrating significant associations with these measures. The CSI-CV exhibits excellent internal consistency, factor structure, and reliability. Its successful cultural adaptation offers valuable insights for improving treatment approaches for patients with CNSLBP.

Molecular Chaperones to Pain Modulators: Heat Shock Proteins the Emerging Players in Chronic Pain Management.

Chronic pain is the most prevailing complex syndrome among clinical disorders affecting approximately 30% of people globally. Various intricate alterations in nociceptive pathways responsible for chronic pain are linked to long-term tissue damage or injury to the peripheral or central nervous systems. These include remolding in the phenotype of cells and fluctuations in the expression of proteins such as ion channels, neurotransmitters, and receptors. Heat shock proteins are important molecular chaperone proteins in cell responses to stress, including inflammation, neurodegeneration, and pain signaling. They play a key role in activating glial and endothelial cells and in the production of inflammatory mediators and excitatory amino acids in both peripheral and central nervous systems. In particular, they contribute to central sensitization and hyperactivation within the dorsal horn of the spinal cord. The expression of some HSPs plays a remarkable role in upregulating pain response by acting as scavengers of ROS, controlling inflammatory cytokines. Different HSPs act by different mechanisms and several important pathways have been implicated in targeting HSPs for the treatment of neuropathic pain including p38-mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases (ERKs), brain-derived neurotrophic factors (BDNF). We summarize the role of HSPs in various preclinical and clinical studies and the crosstalk of HSPs with various nociceptors and other pain models. We also highlighted some artificial intelligence tools and machine learning-assisted drug discovery methods for rapid screening of HSPs in various diseases. Thus, targeting HSPs may provide new therapeutic opportunities for the management of chronic pain conditions and expand our understanding of pain in neurological disorders and other pathological conditions.

Research progress on analgesic mechanism of acupuncture for cancer pain

Cancer pain is one of the common complications in patients with intermediate or advanced cancer, which brings severe sufferings to patients and their families, and also seriously interferes with the anti-tumor process. Acupuncture is an effective method for the treatment of cancer pain, which has the advantages of simple operation, quick effect and fewer side effects, and is widely used in clinic. In this paper, we reviewed the relevant literature on the mechanisms of acupuncture in the treatment of cancer pain both at home and abroad in recent years, and summarized the analgesic mechanisms of acupuncture for cancer pain from the peripheral level and the central level. It is found that acupuncture can relieve cancer pain by regulating immune inflammatory response, expression of ion channels and pain-related receptors, remising central sensitization, activating endogenous pain modulating system and suppressing pain transmission pathways. In addition, we also think that the use of high-throughput multi-omics techniques and neuroimaging methods to detect and analyze the brain areas or body fluids before and after acupuncture should be the focus of acupuncture analgesia research in the future.

Tear Film and Dry Eye Characteristics as Predictors of Photophobia in 374 Patients with Dry Eye Disease

ABSTRACT Purpose To assess the tear film parameters associated with photophobia in dry eye disease (DED). Methods Three hundred seventy-four patients with DED (mean age, 42.2 ± 12.8 years) had their tear film and OSDI scores evaluated using Oculus keratograph 5 M (TMH, NIBUT, Meibography), Lipiview interferometer (LLT), and TearLab osmolarity system. Photophobia scoring from OSDI sheets was used to calculate the odds ratio via multivariate logistic regression analysis. Data from the eye with severely affected NIBUT was used. Results Of 374, 127 had aqueous deficient dry eye disease (ADDE), and 247 had evaporative DED. The mean age, female sex, Schirmer I, TMH, NIBUT, LLT, and tear osmolarity values in patients with photophobia versus no or mild photophobia were 42.2. vs. 40.9 years, 42% vs. 40%, 11.6 vs. 10.5 mm, 0.27 vs. 0.29 mm, 4.6 vs. 4.7s, 60.3 vs. 60.9 nm and 305 vs. 307 mOsm/L, respectively. Multivariate analysis revealed no tear film parameters predictive of photophobia in evaporative DED, whereas tear osmolarity had a weak negative association with photophobia (odds ratio of 0.96, 95% C.I, 0.92–1, p = .04) in ADDE patients. Conclusion Tear film parameters do not predict the presence or absence of photophobia in DED except for a weak inverse association with tear osmolarity in ADDE. This suggests the role of central sensitization in regulating photophobia in DED patients.

Multimodal intervention based on physical exercise, mindfulness, behaviour change and education to improve pain and health in patients with chronic primary low back pain: a study protocol of the HEALTHYBACK randomised controlled trial

The HEALTHYBACK trial is based on a multimodal intervention to determine the effectiveness of a supervised physical exercise, mindfulness, behaviour change and pain neuroscience education programme on several health variables...

Exploring the potential of Fargesin from Chrysanthemum indicum for chronic migraine: in-silico and pharmacokinetic study.

Chronic migraine is recognized by the WHO as one of the most debilitating chronic conditions. It is primarily caused by central sensitization of the trigeminal nucleus caudalis. Key biomarkers associated with migraine include NFkB, IL-1β, CGRP, and iNOS. While CGRP antagonists have proven effective in treating migraines, Chrysanthemum indicum L., a traditional herbal remedy, has not been established as a treatment. To address this, we investigated whether Fargesin, a lignan found in CI, could potentially reduce migraines by targeting these biomarkers. We conducted pharmacokinetic, toxicological, and in-silico studies. Molecular docking studies revealed a strong interaction between Fargesin and CGRP/iNOS. The pharmacokinetic analysis indicated robust intestinal absorption and effective penetration of the blood-brain barrier. In-silico toxicity assessments showed favorable results. Promising interactions with drug targets were observed in bioactivity tests. Fargesin from Chrysanthemum indicum may hold potential as a therapeutic agent for migraines.

Associations Between Sensitivity to Thyroid Hormones and Visceral Adiposity in Euthyroid Adults

Abstract Objectives The study aimed to explore the association between thyroid hormone (TH) sensitivity and obesity assessed by body mass index (BMI) and visceral adiposity index (VAI) in euthyroid adults. Methods This cross-sectional study used the Thyroid Feedback Quantile-based Index (TFQI), TSH index (TSHI), and thyrotrophic T4 resistance index (TT4RI) to indicate central TH sensitivity, and VAI to assess visceral obesity. Participants were categorized according to tertiles. We used logistic and linear regressions to explore the associations stratified by sex. Results The study enrolled 5411 men and 5749 women with normal thyroid function. Men with the highest tertile of TT4RI had 1 kg/m2 higher BMI compared with men with the lowest tertile of TT4RI (P = .001) after adjustment for age, hypertension, hyperlipidemia, diabetes, hyperuricemia, and renal function. There was no significant difference in BMI across tertiles of TFQI and TSHI in men, and TFQI, TSHI, and TT4RI in women after adjustment for other risk factors. TH sensitivity indices were positively related to VAI after adjustment for confounders in women but not in men. There were 1.21 (95% CI, 1.02-1.44; P = .03), 1.43 (95% CI, 1.20-1.70; P &amp;lt; .001), and 1.47 (95% CI, 1.23-1.75; P &amp;lt; .001) times higher odds of having high VAI among women in the highest TFQI, TSHI, and TT4RI tertiles, respectively, compared to women in the lowest tertile. Conclusion Reduced central TH sensitivity was associated with increased visceral adiposity in women but not men. Our findings supplemented the evidence of the importance of TH sensitivity to metabolic disorders, especially among women.

Association between per- and polyfluoroalkyl substance exposures and thyroid homeostasis parameters.

Prevailing studies have shown the disruption effect of per- and polyfluoroalkyl substances (PFAS) on thyroid homeostasis. However, most studies focused on individual thyroid hormones. To explore the associations between PFAS exposures and thyroid homeostasis parameters. A total of 2386 adults from NHANES (2007-2008 and 2011-2012) were included. Thyroid homeostasis parameters included central and peripheral thyroid hormone sensitivity, calculated by thyroid hormones. Multivariable survey-weighted linear regressions were performed to determine the association between PFAS exposure and thyroid homeostasis parameters. The weighted quantile sum (WQS) and the quantile g-computation (QGC) models were used to estimate the mixed effects of co-exposures to PFAS. The ratio of free triiodothyronine/free thyroxine (FT3/FT4) and the sum activity of peripheral deiodinases (SPINA-GD) were positively associated with perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid, perfluorononanoic acid and perfluorohexane sulfonic acid, respectively. However, no significant associations were observed between PFAS exposure and central thyroid sensitivity parameters. PFAS co-exposures was positively associated with FT3/FT4 (β = 0.013, P < 0.001) and SPINA-GD (β = 1.230, P < 0.001) in WQS models. Consistently, PFAS concentrations per quantile was linked to an increase in FT3/FT4 (β = 0.004, P = 0.002) and SPINA-GD (β = 0.392, P = 0.008) in GQC models, with PFOA having the highest weight in all models. This study revealed that PFAS exposures may affect peripheral thyroid hormone sensitivity instead of central among U.S. general adults, enhancing our understanding of the correlation between PFAS exposure and thyroid hormones and providing insights into potential health implications.

Tonic Cold Pain Temporal Summation and Translesional Cold Pressor Test-Induced Pronociception in Spinal Cord Injury: Association with Spontaneous and Below-Level Neuropathic Pain.

Background/Objectives: Although increased nociceptive excitability and deficient endogenous pain modulation are considered key features of pronociception and central sensitization, their contribution to neuropathic pain (NP) characteristics in SCI is unclear. The aim of this study was to characterize tonic cold perception and endogenous pain modulation in individuals with and without SCI-NP, considering the stage and severity of SCI and, secondarily, NP phenotype. Methods: Temporal summation of pain (TSP) and neuropathic features were assessed using the numerical rating scale (NRS) and Douleur Neuropathique 4 screening questionnaire (DN4) during the tonic cold pressor test (CPT, 12 °C 60 s) applied to the dominant hand and foot. CPT-induced pronociception was assessed as change in algometer pressure pain thresholds (PPTs) measured at the V2, C6, and L4 dermatomes. Results: A total of 72 individuals were recruited (age-sex-matched noninjured, n = 24; SCI-NP, n = 24; SCI-noNP, n = 24 [AIS A: n = 12, AIS B-D: n = 12; subacute SCI: n = 12, chronic SCI: n = 12]). TSP in response to the foot CPT was higher in subacute compared to chronic incomplete SCI-NP, while TSP to the hand CPT was significantly higher in chronic compared to the subacute complete SCI-NP group. Evoked pain intensity during the hand CPT correlated with duration of below-level SCI-NP. The hand CPT induced widespread pronociception (lower PPT), which correlated with 7-day non-evoked (spontaneous) pain intensity in individuals with incomplete SCI-NP. Individuals with below-level NP, but not at-level NP, showed higher TSP during the foot CPT and greater hand CPT-induced L4 dermatome pronociception. Conclusions: Collectively, measurements of above and below-level temporal summation of pain and translesional-induced pronociception in the SCI-NP group highlight the role of these mechanisms in widespread central sensitization, spontaneous pain intensity, and spinothalamic tract hyperexcitability, especially in individuals diagnosed with below-level NP.

Altered parasympathetic outflow and central sensitization response to continuous pain in cyclic vomiting syndrome: a functional magnetic resonance imaging study.

Cyclic vomiting syndrome (CVS) is a disorder of brain-gut interaction characterized by recurrent episodes of nausea and vomiting interspersed with asymptomatic periods and associated with autonomic nervous system dysfunction. We examined the dysautonomic response to noxious stimuli seen in CVS patients using our previously validated approach to integrate peripheral autonomic outflow metrics, temporal summation of pain, and brain fMRI. BOLD fMRI and ECG were acquired from CVS patients and healthy adults during a rest condition and a sustained cuff pressure pain stimulus at the leg. After the latter scan, participants rated pain for the full 6-minute pain stimulus as well as first, middle, and last two-minutes to calculate temporal summation. During sustained pain, patients (n=13) exhibited greater reduction in heart rate variability within the high-frequency range (HF-HRV) and reduced anticorrelation between HF-HRV and fMRI signal in the anterior insula, pregenual anterior cingulate cortex, and ventrolateral and dorsolateral prefrontal cortex relative to healthy adults (n=13). Compared to healthy adults (n=14), patients (n=14) exhibited increasing pain intensity over the course of sustained cuff pressure. Seed-based functional connectivity analysis revealed for healthy adults (n=13), pain sensitization correlated with pain-induced increases in connectivity between primary somatosensory cortex and regions of interest in both left anterior insula/posterior orbitofrontal cortex and right pre-supplementary motor area, while this correlation was disrupted in CVS (n=10). Our results support altered central coding of nociceptive stimuli and autonomic responsivity of CVS patients in key brain regions implicated in autonomic control and interoception.

Twisted clustered pinhole collimation for improved high-energy preclinical SPECT/PET

Objective.Advanced pinhole collimation geometries optimized for preclinical high-energyɣimaging facilitate applications such asɑandßemitter imaging, simultaneous multi-isotope PET and PET/SPECT, and positron range-free PET. These geometries replace each pinhole with a group of clustered pinholes (CPs) featuring smaller individual pinhole opening angles (POAs), enabling sub-mm resolution imaging up to ∼1 MeV. Further narrowing POAs while retaining field-of-view (FOV) may enhance high-energy imaging but faces geometrical constraints. Here, we detail how the novel twisted CPs (TCPs) address this challenge.Approach.We compared TCP and CP collimator sensitivity at equal system resolution (SR) and SR at matched sensitivity by tuning pinhole diameters for18F (511 keV) and89Zr (909 keV). Additionally, simulated Derenzo phantoms at low activity (LA: 12 MBq ml-1) and high activity (HA: 190 MBq ml-1) levels, along with uniformity images, were compared to assess image resolution and uniformity.Main results.At equal SR, TCP increased average central FOV sensitivity by 15.6% for18F and 29.4% for89Zr compared to CP. Image resolution was comparable, except for89Zr at LA, where TCP resolved 0.80 mm diameter rods compared to 0.90 mm for CP. Image uniformity was equivalent for18F, while for89Zr TCP granted a 10.4% improvement. For collimators with matched sensitivity, TCP improved SR by 6.6% for18F and 17.7% for89Zr while also enhancing image resolution; for18F, rods distinguished were 0.65 mm (CP) and 0.60 mm (TCP) for HA, and 0.70 mm (CP and TCP) for LA. For89Zr, image resolutions were 0.75 mm (CP) and 0.65 mm (TCP) for HA, and 0.90 mm (CP) and 0.80 mm (TCP) for LA. Image uniformity with TCP decreased by 18.3% for18F but improved by 20.1% for89Zr.Significance.This study suggests that the TCP design has potential to improve high-energyɣimaging.

Active Neurodynamic Technique at Home in Patients with Knee Osteoarthritis: An Open Single Arm Clinical Trial.

Background and Objectives: Knee osteoarthritis (KO) stands as the third leading cause of disability among the elderly, causing pain, reduced quality of life, and decreased functionality. The objective of this study is to assess the effects of an active neurodynamic technique programme at home on pain, quality of life, and function among individuals with KO. Materials and Methods: Thirty-five participants (69.7% women) aged ≥50 years with KO (Kellgren-Lawrence grades I-II) performed a femoral nerve mobilization programme at home for 6-8 weeks (20 repetitions per day). Pain intensity, using the numerical rating scale (NRS), pressure pain thresholds (PPTs), central sensitization inventory (CSI), temporal assessment, pain modulation, Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 12-item Short Form Survey questionnaire (SF-12) were collected before, after the intervention, and at one, three, six, and twelve months. Results: Participants improved significantly in pain (p < 0.05), with the improvement maintained throughout the follow-up in the NRS and for at least one month in the PPT. There were also statistically significant (p < 0.05) improvements in all subscales of the KOOS, which were maintained throughout the follow-up. Improvements were also found in the CSI and CPM. Conclusions: A home-based active neurodynamic programme for the femoral nerve has been demonstrated to yield positive effects on pain and function in patients with KO.

Exploring signs of central sensitization in adolescents with hypermobility Spectrum disorder or hypermobile Ehlers-Danlos syndrome.

Hypermobility Spectrum Disorder (HSD) and Hypermobile Ehlers-Danlos Syndrome (hEDS) are two overlapping heritable connective tissue disorders characterized by joint hypermobility, chronic pain, impaired body perception, and musculoskeletal symptoms. Central sensitization has been proposed as a plausible explanation for symptoms like widespread pain, fatigue, mood disorders, and sleep disturbances in patients with HSD/hEDS. The aim of this study was to investigate signs of central sensitization, including exercise-induced hypoalgesia (EIH), and fatigue severity in adolescents with HSD/hEDS. In this prospective, experimental, case-control study, thirty-seven adolescents with HSD/hEDS and 47 healthy adolescents (all aged 13-17 years) were included. Pressure pain thresholds (PPTs) were measured at four muscle groups using a pressure algometer. EIH was evaluated by measuring PPTs on two muscle groups immediately after an exercise test on a bicycle ergometer. Participants also completed questionnaires on fatigue and cognitive/emotional factors. The study demonstrated significantly lower PPTs in four different muscle groups in adolescents with HSD/hEDS compared to the healthy control group. Both groups achieved a significantly higher PPTs after exercise in the muscle involved in the activity. Adolescents with HSD/hEDS reported higher fatigue levels and more cognitive/emotional difficulties than the control group. Adolescents with HSD/hEDS showed generalized hyperalgesia measured through PPTs at different body sites. EIH was partly affected in adolescents with HSD/hEDS, presenting as unchanged pain sensitivity in the remote muscle. Pain should be considered as a phenomenon that is influenced by different biopsychosocial factors, including possible central sensitization, which increase its complexity. This study breaks new ground by showing signs of central sensitization, including diminished EIH, in adolescents with HSD or hEDS. Given that exercise is a key element in pain management, these findings offer valuable insights when developing treatment plans for adolescents with HSD or hEDS.