Sensitization Research Articles

The profile beyond leg pain: In basis of central sensitization, kinesiophobia, and body awareness in patients with chronic venous disease.

Objective: Leg pain has long been underestimated despite being one of the most important symptoms of chronic venous disease (CVD). Studies investigating leg pain and psychosocial profile in CVD are limited. The study aimed to investigate leg pain, central sensitization, kinesiophobia, and body awareness in patients with CVD. Methods: The ninety-eight patients (80 female, 18 male) diagnosed with CVD were included in the study. The severity of leg pain was evaluated with the Visual Analog Scale (VAS). The patients were assessed with the Central Sensitization Inventory (CSI-A and B) for central sensitization-related symptoms and -positivity, the Body Awareness Questionnaire (BAQ) for body awareness, and the Tampa Kinesiophobia Scale (TKS) for kinesiophobia. The cut-off score was admitted as 41 for TKS. Results: The leg pain (mean (SD) = 4.3 ± 2) and body awareness (mean (SD) = 82.4 ± 22) were moderate levels in patients with CVD. Nearly half of the patients (n = 46, 46.9%) had both central sensitization positivity and elevated kinesiophobia (n = 46, 47%). The CSI was correlated with the VAS (r = 0.32, p = .001), TKS (r = 0.40, p < .001), and BAQ (r = 0.20, p = .048). Significant correlations were determined between Body Mass Index and TKS (r = 0.48, p < .001) and BAQ (r = -0.31, p = .002). Also, the patients with a TKS score ≥41-points had higher CSI-A scores (p = .002) than those with a TKS score< 41. Conclusions: Leg pain, central sensitization, and kinesiophobia are commonly seen in patients with CVD, and central sensitization seems to have a negative effect on leg pain, kinesiophobia, and body awareness. The profile beyond pain should be evaluated in detail, and various rehabilitation strategies need to be developed to manage central sensitization, interoception, kinesiophobia, and weight control in patients with CVD.

Assessing signs of central sensitization: A critical review of physiological measures in experimentally induced secondary hyperalgesia.

Central sensitization (CS) is believed to play a role in many chronic pain conditions. Direct non-invasive recording from single nociceptive neurons is not feasible in humans, complicating CS establishment. This review discusses how secondary hyperalgesia (SHA), considered a manifestation of CS, affects physiological measures in healthy individuals and if these measures could indicate CS. It addresses controversies about heat sensitivity changes, the role of tactile afferents in mechanical hypersensitivity and detecting SHA through electrical stimuli. Additionally, it reviews the potential of neurophysiological measures to indicate CS presence. Four databases, PubMed, ScienceDirect, Scopus and Cochrane Library, were searched using terms linked to 'hyperalgesia'. The search was limited to research articles in English conducted in humans until 2023. Evidence for heat hyperalgesia in the SHA area is sparse and seems to depend on the experimental method used. Minimal or no involvement of tactile afferents in SHA was found. At the spinal level, the threshold of the nociceptive withdrawal reflex (RIII) is consistently reduced during experimentally induced SHA. The RIII area and the spinal somatosensory potential (N13-SEP) amplitude are modulated only with long-lasting nociceptive input. At the brain level, pinprick-evoked potentials within the SHA area are increased. Mechanical pinprick hyperalgesia is the most reliable behavioural readout for SHA, while the RIII threshold is the most sensitive neurophysiological readout. Due to scarce data on reliability, sensitivity and specificity, none of the revised neurophysiological methods is currently suitable for CS identification at the individual level. Gathering evidence for CS in humans is a crucial research focus, especially with the increasing interest in concepts such as 'central sensitization-like pain' or 'nociplastic pain'. This review clarifies which readouts, among the different behavioural and neurophysiological proxies tested in experimental settings, can be used to infer the presence of CS in humans.

Psychedelics as novel therapeutic agents for chronic pain: mechanisms and future perspectives

Chronic neuropathic pain is a significant public health issue affecting an estimated 1.5 billion individuals worldwide. The mechanisms underlying chronic pain are multifaceted and not fully understood. Chronic pain amplifies specific neural pathways through peripheral and central sensitization triggered by repeated exposure to noxious stimuli, ultimately resulting in physical and emotional pain. Traditional treatment options targeting these mechanisms, such as opioid and non-opioid analgesics, are associated with adverse effects, addiction, and suboptimal pain relief. Using psychedelics to treat chronic pain is an area of growing interest. While psychedelic substances, such as psilocybin, lysergic acid diethylamide, mescaline, and 3,4-methylenedioxymethamphetamine are primarily associated with recreational use or spiritual practices, emerging evidence suggests their potential therapeutic benefits for various mental health disorders, including chronic pain. Psychedelics alter pain perception by directly activating serotonin receptors, exerting anti-inflammatory effects, enhancing descending inhibition, opening a window of neuroplasticity, and facilitating synaptic remodeling. This review mainly elucidates the ongoing research regarding the psychedelic mechanisms of action, pharmacology, clinical applications, and therapeutic potential in treating neuropathic pain.

The effect of fibromyalgia syndrome on female patients diagnosed with chronic migraine

ObjectiveTo compare pain, quality of life, sleep, anxiety and depression, central sensitization, and functionality between chronic migraine (CM) patients with comorbid fibromyalgia syndrome (FMS) and patients with CM alone. MethodThirty three female patients with CM and thirty three female patients with CM+FMS were enrolled in the study. Demographic and clinical characteristics of the patients were recorded. FM was diagnosed based on the 2016 American College of Rheumatology diagnostic criteria. All participants were evaluated with Allodynia Symptom Checklist, Short Form-36 (SF-36), Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT-6) questionnaires, and Central Sensitization Inventory (CSI). FM patients were also evaluated with Fibromyalgia Impact Questionnaire (FIQ). ResultsThe average number of headache days was significantly higher in patients with CM+FMS (p = 0.006). Among migraine accompanying symptoms, the number of patients with phonophobia was significantly higher in patients with CM+FMS (p = 0.008). While CSI score was 39.0 ± 11.7 in CM patients, it was 52.2 ± 9.2 in CM+FMS patients. CSI scores were higher in CM+FMS patients (p < 0.001). SF-36 sub-cores, including physical function, energy/fatigue, emotional well-being, and general health scores, were lower in CM+FMS patients (p < 0.05). Sleep duration was significantly lower and use of medication to sleep was more common in same group (p < 0.05). FIQ score in CM+FMS patients was associated with quality of life scores, sleep quality, anxiety, and central sensitization scores (p < 0.05). ConclusionIn patients with chronic migraine, FMS comorbidity negatively affects the quality of life and significantly increases central sensitization.

Fibromyalgia progression and association with other diseases and inheritance with management practices in humans

Fibromyalgia is a widespread pain disorder characterized by chronic, diffuse pain, about 1 to 5% around world. While more prevalent in women and adults, it can also manifest in children and adolescents. The specific pathophysiology of fibromyalgia remains unclear, but it is associated with neuronal over sensitization, reduced conditioned pain modulation, cognitive dysfunction, memory loss, and impaired information processing. It has now been categorized as a somatic symptom disorder. This study aimed to investigate fibromyalgia, focusing on its potential hereditary connections and management practices. A key pathophysiological aspect of fibromyalgia is central sensitization, marked by increased functional connectivity with pre-receptive brain areas, decreased connectivity with antinociceptive areas, and alterations in central nervous system neurotransmitters, also in size and shape of specific brain areas. Fibromyalgia is not directly inherited from parents to offspring, it does exhibit a tendency to cluster within families. The serotonin transporter gene, characterized by single nucleotide polymorphism with "S" (short) allele, is more prevalent in individuals with fibromyalgia and psychological distress. In conclusion, fibromyalgia is a widespread pain disorder with a substantial impact on the central nervous system, resulting in significant disability and an elevated risk of chronic diseases. Early diagnosis and intervention can minimize the impact of fibromyalgia. Physical therapy and non-drug therapies should be customized for each patient. The FDA has approved three drugs including pregabalin, duloxetine, and milnacipran for fibromyalgia treatment.

Visual Outcomes and Patient Satisfaction of Enhanced Monofocal Intraocular Lens in Phacovitrectomy for Idiopathic Epiretinal Membrane.

To evaluate the clinical outcomes and patient satisfaction after implantation of an enhanced monofocal intraocular lens (TECNIS Eyhance ICB00) in patients with idiopathic epiretinal membrane (ERM) who underwent cataract surgery with pars plana vitrectomy (PPV). This is a single-center, retrospective, comparative study. In total, 61 eyes of 61 patients with idiopathic ERM and cataracts were included. We measured the uncorrected near and intermediate visual acuity (UNVA and UIVA), uncorrected and corrected distance visual acuity (UDVA and CDVA), central macular thickness, defocus curves, and contrast sensitivity 3-6 months after the surgery. Overall patient satisfaction was assessed using a questionnaire at the 1-month follow-up visit. The ICB00 group showed better near and intermediate visual acuity than the monofocal group (TECNIS ZCB00); however, no statistically significant differences were found between the groups. The ICB00 group exhibited wider defocus curves at near to far distances (-3.0 to +2.0 D) than the ZCB00 group. There were no significant differences in the results of the contrast sensitivity test, dysphotopsia, spectacle dependence, or patient satisfaction between the two groups. In combined PPV and cataract surgery for ERM patients, ICB00 resulted in good visual acuity with a smoother defocus curve compared to the ZCB00 group.

Vortioxetine reduces the development of pain‐related behaviour in a knee osteoarthritis model in rats: Involvement of nerve growth factor (NGF) down‐regulation

AbstractBackground and PurposeVortioxetine, a multimodal‐acting antidepressant, has recently shown analgesic properties. We aimed to investigate its prophylactic effect in the osteoarthritis (OA) model and gain insights into the underlying molecular mechanisms. Duloxetine was studied as a reference.Experimental ApproachIn the monoiodoacetate (MIA)‐induced rat model of knee OA, pain‐related behaviour was assessed in weight‐bearing and Von Frey tests. Antidepressants were administered orally once daily for 28 days. Gene expression of pain‐related mediators (Ngf, Il‐1β, Tnf‐α, Bdnf, and Tac1 encoding substance P) and oxidative stress parameters were determined after completion of the treatment/behavioural testing protocol.Key ResultsVortioxetine and duloxetine dose dependently reduced weight‐bearing asymmetry and mechanical hyperalgesia of the paw ipsilateral to the MIA‐injected knee. Vortioxetine reduced the increased Ngf mRNA expression in the MIA‐injected knees to the level in sham‐injected counterparts. It reduced oxidative stress parameters in the affected knees, more effectively in females than males. Duloxetine showed no effect on Ngf mRNA expression and oxidative stress. Both antidepressants decreased mRNA expression of pain‐related mediators in the lumbar L3–L5 ipsilateral DRGs and spinal cords, which were up‐regulated in MIA‐injected rats. This effect was male‐specific.Conclusion and ImplicationsVortioxetine may be effective against the development of chronic pain in OA. Its antihyperalgesic effect may be mediated, at least in part, by normalization of NGF expression in the affected joint. Decrease of localized oxidative stress and of expression of pain‐related mediators that contribute to central sensitization are also involved in vortioxetine's antihyperalgesic effect, in a sex‐specific pattern.

Efficacy of galcanezumab in migraine central sensitizatio

Galcanezumab, a monoclonal antibody targeting the calcitonin gene-related peptide pathway (CGRP mAb), acts peripherally due to its large size. However, recent studies have suggested that CGRP mAbs may also have a central mode of action. This study aimed to evaluate the central effects of galcanezumab on migraine central sensitization.This prospective real-world study was conducted at three headache centers in Japan between May 2021 and May 2022. Patients treated with galcanezumab for migraines were included in the study. The primary outcome was the change in the validated Central Sensitization Inventory (CSI) score from baseline to six months of treatment. We also assessed changes in the Allodynia Symptom Checklist (ASC-12) score. Eighty-six patients with migraine (73 female and 13 male) were analyzed. At 6 months, CSI and ASC-12 scores were significantly reduced compared to baseline (CSI: 36.0 vs. 29.3, p < 0.001; and ASC-12: 5.55 vs. 4.26, p < 0.01). Furthermore, these effects were observed as early as three months of treatment. In this study, we demonstrated the real-world efficacy of galcanezumab in improving central sensitization in migraine, with significant effects seen in the early phase of treatment.Please check and confirm whether the corresponding author mail ID is correctly processed We checked it. And, please kindly re-check !!!! !!! To use this Article for commercial purposes should be okay.!!! We asked you to publish this article with the following license; Creative Commons licence CC BY: This licence allows readers to copy, distribute and transmit the Article as long as it is attributed back to the author. Readers are permitted to alter, transform or build upon the Article, and to use the Article for commercial purposes.Please confirm the inserted city name is correct in affiliation 3 and amend if necessary.Checked.Per style, a structured abstract is not allowed so we have changed the structured abstract to an unstructured abstract. Please check and confirm.We Checked. And again, please kindly make sure the followings;!!! Please kindly re-check !!! To use this Article for commercial purposes should be okay.!!! We asked you to publish this article with the following license; Creative Commons licence CC BY: This licence allows readers to copy, distribute and transmit the Article as long as it is attributed back to the author. Readers are permitted to alter, transform or build upon the Article, and to use the Article for commercial purposes.Trial registration: This study was registered with UMIN-CTR on May 2, 2021 (UMIN000044096).

Effect of autologous serum after amniotic membrane transplantation for persistent corneal ulcers.

To investigate the effect of adding autologous serum eye drops to the postoperative regime after amniotic membrane transplantation for severe persistent corneal ulcers. Forty eyes of 40 patients with persistent corneal ulcers were randomly assigned to artificial tears (sodium hyaluronate 0.2%, ATs group, n=20) or autologous serum eye drops (ASEDs, n=20) following treatment with amniotic membrane transplantation. Digital slit lamp images were acquired from all patients before and 30d post treatment. The area with fibrovascular tissue was calculated using Image J. Central corneal sensitivity was assessed by Cochet-Bonnet aesthesiometry before and one month after treatment. Scar tissue transparency was assessed with a novel optical densitometry. Mean age of patients was 61.65±16.47y and 57.3±19.11y in the ATs group and ASEDs group, respectively. Twenty-two male and 18 female patients were included in the study. The improvement in visual acuity was significantly greater in the ASEDs group (0.14±0.04) than the ATs (0.08±0.04; P=0.00046). Cochet-Bonnet aesthesiometry improved significantly after treatment with a similar rate between groups. There were no statistically significant differences in the area of postoperative fibrovascular tissue between the two groups (P=0.082). The success rate in the two groups was similar. The difference in densitometry between the ATs and ASEDs group was statistically significant (P=0.042) with greater reduction from baseline in the ASEDS group. Autologous serum eye drops can lead to better visual acuity, more stable results and improved densitometry and should be considered in the postoperative care following amniotic membrane transplantation.

The Association Between the Central Sensitisation Inventory and Temporomandibular Disorders Is Confounded by Migraine, Depression, Widespread Pain and Parafunction. A Cross-Sectional Telehealth Study.

Temporomandibular disorders (TMDs) are conditions that involve the temporomandibular joints, masticatory muscles, and associated tissues, causing orofacial pain. Central sensitisation (CS) is a relevant part of the TMD pathophysiology. Migraine, psychological aspects, parafunctional oral habits and widespread pain are commonly associated with both TMD and CS and could confound the association between them. To investigate the association between painful TMD and the Central Sensitisation Inventory (CSI) score, and to assess the presence of confounders in this association. Cross-sectional study that assessed women with and without orofacial pain complaints using telehealth. The TMD Pain Screener and an online physical examination determined the presence of painful TMD. The following questionnaires were applied: CSI, Headache Screening Questionnaire, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Oral Behavior Checklist, Jaw Functional Limitation Scale and the Nordic musculoskeletal questionnaire. A single regression investigated the association between the CSI score and TMD, and a multiple regression investigated the effect of the other outcomes as possible confounders. Confounding was considered present when the association between TMD and the CSI score changed more than 10% after adding a possible confounder to the regression model. Forty-two women with painful TMD and 53 without TMD were included. There was a significant association between the CSI score and the presence of painful TMD (R2 = 0.639; p < 0.001). This association changed when the following outcomes were added to the model: presence of migraine, symptoms of depression, widespread pain and parafunctional oral habits. The positive association between TMD and the CSI score was confounded by migraine, symptoms of depression, widespread pain and parafunctional oral habits.

Pain Is Modulated Differently Between Females with and without Patellofemoral Pain: Factors Related to Sensitization.

Patellofemoral pain (PFP) has poor long-term recovery outcomes. Central sensitization describes central nervous system changes altering pain modulation, which can complicate recovery (poorer prognosis, worse function). Signs of central sensitization include amplified pain facilitation, pain hypersensitivity, and impaired pain inhibition, which can be measured with temporal summation of pain (TSP), pressure pain thresholds (PPTs) and conditioned pain modulation (CPM), respectively. Sex differences exist for these test responses, but female-only PFP investigations of sensitization are uncommon. Understanding pain modulation in females with PFP could improve treatment protocols. To determine whether females with PFP exhibit signs of central sensitization (greater TSP, lower PPTs, reduced CPM) compared to pain-free females. Cross-sectional Setting: Laboratory Patients or Other Participants: Thirty-three females [(20 PFP, 13 pain-free); Age: PFP 29.2 ± 7 years, pain-free 28 ± 7 years; Height: PFP 166.7 ± 5.9cm, pain-free 166 ± 9.5cm, Mass: PFP 66.7 ± 9.6kg, pain-free 69.3 ± 7.5kg). TSP was assessed with ten punctate stimuli applied to the knee and calculated by the difference in pain intensity between beginning and end responses. PPTs were tested at four sites [3 for local hypersensitivity (knee), 1 for widespread hypersensitivity (hand)]. CPM was conducted by comparing PPTs during two conditions (baseline, ice immersion). CPM response was defined as the percent difference between conditions. Between-group differences in TSP response were analyzed with a Welch's test. Separate Welch's tests analyzed group comparisons of PPTs and CPM responses at four sites. Females with PFP exhibited greater TSP response (P=0.019) and lower CPM response at patella center (P=0.010) and hand sites (P=0.007) than pain-free females. PPT group differences were not observed at any site (P>0.0125). Females with PFP modulate pain differently than pain-free females. Clinicians should recognize signs of central sensitization and their potential impact on treatment options.

The effect of inner limiting membrane peeling on visual fields: Unravelling a source of bias in glaucoma management

Abstract: Pars plana vitrectomy (PPV) with inner limiting membrane (ILM) peeling aims to improve visual function. Previous studies have focused on visual acuity, often neglecting visual field (VF) changes. This systematic review examines VF changes after PPV with ILM peeling in patients with epiretinal membrane (ERM) or macular hole (MH), including those with glaucoma, who have preexisting VF damage, to identify potential biases in glaucoma management. The inclusion criteria were as follows: (A) Patients undergoing ILM peeling for ERM or MH and (B) VF outcomes assessed through standard automated perimetry (SAP) or Goldmann kinetic perimetry. Exclusions were non-English studies and those with fewer than 30 subjects. Data included retinal disease, demographics, VF outcomes (mean deviation [MD], pattern standard deviation, and central VF sensitivity [CVFS]), study design, and use of stains. Out of 612 studies, 23 met our criteria. Of these, four included glaucoma patients and seven involved concomitant phacoemulsification. In glaucoma patients, two studies showed MD improvement in the central 24°, while one showed deterioration in the central 10°, linked to worse preoperative MD and older age. Among studies without glaucoma patients, three of eight using SAP reported increased VF defects (VFDs); two showed lower outer nasal CVFS postoperatively. Indocyanine green staining was linked to higher VFD incidence while triamcinolone acetonide or tryptane blue staining led to no significant VFDs. The nasal half of the central VF was more affected, possibly due to retinal ganglion cell distribution. Further prospective studies, including randomized controlled trials, are needed to better understand ILM-peeling effects.

Exploring Facial Somatosensory Distortion in Chronic Migraine: The Role of Laterality and Emotion Recognition—A Cross-Sectional Study

Background: In addition to being highly distressing, chronic migraine headaches are a major socioeconomic challenge. Like other pain syndromes, migraine headaches are associated with psychological and physiological impairments, including sensorimotor and somatosensory deficits. Aim: This study aims to explore whether patients with high-frequency or chronic migraine differ from a healthy population in the areas of laterality recognition (LAT) and facial emotion recognition (FER) and whether there are correlations between these areas and central sensitization of pain and psychological components like stress, depression, anxiety, and alexithymia. Methods: Using a cross-sectional design, individuals with high-frequency or chronic (ICHD classification) migraine (migraine group MG = 45) and healthy individuals (control group CG = 25) were studied using LAT testing (hand, neck, and face); FER testing; and questionnaires, including the Central Sensitization Inventory (CSI) and the Toronto Alexithymia Scale (TAS-20). Results: Data from 70 participants were collected for analysis. Statistically significant differences were found only in the assessment of central sensitization (p &lt; 0.001). Weak to moderate monotonic correlations were found for the MG, especially between alexithymia detection (TAS-20) and facial emotion recognition (FER test). Discussion: The methodological procedure and its accompanying challenges can be seen as limitations of this study. The lack of significant effects must be mentioned, but the selection of the collected questionnaires, the uniform diagnostics, and the statistical processing of a large amount of data represent methodological strengths. Conclusion: The CSI and the TAS-20 could be used in combination with FER to assess chronic migraine. Implementing the described sensorimotor parameters as a therapeutic intervention requires further investigation.

The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due to the similarity of its symptoms with those of overactive bladder and acute bacterial cystitis, patients often face misdiagnosis and delayed appropriate treatment. Hunner's (HIC) and non-Hunner's IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. Treatment of IC/BPS should involve identifying the different clinical phenotypes and underlying pathophysiology causing clinical symptoms and developing strategies tailored to the patient's needs. This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. Various bladder treatment modalities are explored, including glycosaminoglycan replenishment, botulinum toxin A injection, platelet-rich plasma injection, low-energy shock waves, immunosuppression, and low-dose oral prednisolone. Pelvic floor muscle physiotherapy and bladder therapy combined with psychiatric consultation can help alleviate psychological stress and enhance the quality of life of patients with IC/BPS. Elucidating the pathological mechanisms and exploring diverse treatment options would help advance the care of individuals suffering from this challenging bladder condition.

Actualización en el manejo de gonartrosis: Revisión bibliográfica

Gonarthrosis is a chronic-degenerative disease that involves the entire joint and its components, mainly affecting the articular cartilage, producing its degeneration and bone hyperplasia. About 50-60% of older adults experience symptoms of OA. The objective of this research is to discover new therapeutic options for gonarthrosis, in addition to expanding knowledge about intra-articular infiltration by describing the substances available for this therapy. An electronic search of scientific articles published from January 2018 to April 2024 was carried out in the PubMed, Scopus, Web of Science and ScieLO databases. Currently there are several options for the treatment of OA, from physiotherapy, pharmacotherapy to surgery. Intra-articular drug administration is a new therapeutic approved by the FDA, among its advantages are local bioavailability, reduced systemic drug exposure, fewer adverse events and reduced costs. Some of the substances used are glucocorticoids, hyaluronic acid, ozone and platelet-rich plasma, which reduce pain and inflammation, increasing the patient's quality of life. It is concluded that botulinum toxin decreases central and peripheral sensitivity, reducing pain in the short term. The use of hyaluronic acid as a vehicle for the application of gold microparticles has decreased symptoms in the short and long term, however, further studies are required to evaluate its effectiveness on the control of other symptoms.

Characterization of pain and somatization and its relationship with psychopathology in early onset psychosis

BackgroundEarly onset psychosis (EOP) frequently presents with a severe clinical phenotype and poor long-term prognosis. Clinical experience suggests that individuals with EOP have abnormal pain and somatosensory processing, yet relative to adult-onset psychosis, pain and somatic sensory processing in EOP have rarely been studied. MethodsThe history of two characteristic patients is described to illustrate clinical presentations of pain in EOP patients. Furthermore, 31 patients with EOP were studied with self-reported questionnaires informing on pain severity, pain catastrophizing, central sensitization, and somatization. Structured clinical interviews were administered to confirm Diagnostic and Statistical Manual of Mental Disorders-5 EOP diagnosis and the patient's dimensions of psychopathology were measured by the Brief Psychiatric Rating Scale (BPRS). ResultsOut of 31 EOP patients, 22 reported distressing pain, where higher pain severity corresponded with greater BPRS total and affectivity and resistance subscale scores. The degree of psychopathology was associated (N = 31; p < 0.05, FDR-corrected) with the magnitude of pain catastrophizing, central sensitization, and somatization. Multivariate analysis revealed relationships (N = 31; p < 0.05, FDR-corrected) between BPRS subscale (negative symptoms and activation) scores with somatization severity. The observed associations occurred independent of antipsychotic medication usage as quantified by chlorpromazine equivalent doses. ConclusionsPain and somatosensory symptoms could be a frequent cause of distress in patients with EOP and their severity associated with the degree of psychopathology. Future studies should determine if treating pain and somatic symptoms in EOP patients can lead to better control of psychosis as well as improve quality of life.

Transcriptomic changes in the hypothalamus of mice with chronic migraine: Activation of pathways associated with neuropathic inflammation and central sensitization

Chronic migraine is a common central nervous system disorder characterized by recurrent, pulsating headaches. However, the extent and mechanisms of hypothalamic involvement in disease progression have not been thoroughly investigated. Herein, we created a chronic migraine mouse model using repeated intraperitoneal injections of nitroglycerin. We performed transcriptomic sequencing on the hypothalamus of mice with chronic migraine and control mice under normal physiological conditions, followed by differential gene set enrichment and functional analysis of the data. Additionally, we examined the intrinsic connection between chronic migraine and sleep disorders using transcriptomic sequencing data from sleep-deprived mice available in public databases. We identified 39 differentially expressed genes (DEGs) in the hypothalamus of a mouse model of chronic migraine. Functional analysis of DEGs revealed enrichment primarily in signaling transduction, immune-inflammatory responses, and the cellular microenvironment. A comparison of the transcriptomic data of sleep-deprived mice revealed two commonly expressed DEGs. Our findings indicate that the hypothalamic DEGs are primarily enriched in the PI3K/AKT/mTOR pathway and associated with the NF-κB/NLRP3/IL-1 β pathway activation to maintain the central sensitization of the chronic migraine. Chronic migraine-induced gene expression changes in the hypothalamus may help better understand the underlying mechanisms and identify therapeutic targets.

Can assessment of human assumed central sensitisation improve the predictive accuracy of the STarT Back screening tool in acute low back pain?

BackgroundThe STarT Back Screening Tool (SBT) is recommended to provide risk-stratified care in low back pain (LBP), yet its predictive value is moderate for disability and low for pain severity. Assessment of human assumed central sensitisation (HACS) in conjunction with the SBT may improve its predictive accuracy. ObjectivesTo examine whether assessment of HACS in acute LBP improves the predictive accuracy of the SBT for LBP recovery at six months in people with acute non-specific LBP. DesignA prospective longitudinal study. MethodData were drawn from the UPWaRD study. One hundred and twenty people with acute non-specific LBP were recruited from the community. Baseline measures included SBT risk status, nociceptive flexor withdrawal reflex, pressure and heat pain thresholds and conditioned pain modulation. Primary outcome was the presence of LBP (pain numeric rating scale ≥1 and Roland Morris Disability Questionnaire score ≥3) at six-month follow-up. Regression coefficients were penalised using the least absolute shrinkage and selection operator technique to select predictor variables. Internal validation was performed using ten-fold cross-validation. Results/findingsSBT risk status alone did not predict the presence of LBP at six months (area under receiver operating characteristic curve [AUC] = 0.58). Adding measures of HACS to the SBT did not improve discrimination for whether LBP was present at six months (AUC = 0.59). ConclusionsThis study confirmed the suboptimal predictive accuracy of the SBT, administered during acute LBP, for LBP recovery at six months. Assessment of HACS in acute LBP does not improve the predictive accuracy of the SBT.

Impact of Central Sensitization on Clinical and Functional Aspects of Psoriatic Arthritis.

Background/Objectives: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by peripheral arthritis, enthesitis, spondylitis and psoriasis. The objective of this study was to examine the prevalence of central sensitization (CS) and its impact on the clinical and functional aspects of PsA. Methods: Adult patients with PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria were included in this cross-sectional observational study. The Central Sensitization Inventory (CSI) was used to assess the presence of CS. The study evaluated the impact of CS on individuals by analyzing many factors including demographic information, laboratory findings, clinical features, disease activity, quality of life, severity of sleeplessness, frequency of depression and anxiety. The patients were categorized into distinct groups based on the existence and intensity of CS, and a comparative analysis was conducted on their respective outcomes. Results: A total of 103 PsA patients with a mean age of 43.2 (SD: 6.7) years and including 42 (40.8%) males were included. The mean CSI score was 45.4 (SD: 15.1), and 67 (65.1%) patients had CS. The logistic regression analysis revealed that the variables Psoriasis Area Severity Index (PASI), General Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI) exhibit considerable predictive power in relation to the outcome variable CS (p < 0.05). PASI was observed as the most important variable in predicting CS (OR 9.70 95% CI: 1.52-62.21). Conclusions: CS has demonstrable efficacy in influencing laboratory, clinical, and functional markers among individuals with PsA. When assessing pain sensitivity in these patients, it is important to take into account the presence of CS.

Identifying microRNAs Possibly Implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Review.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are chronic syndromes of unknown etiology, accompanied by numerous symptoms affecting neurological and physical conditions. Despite frequent revisions of the diagnostic criteria, clinical practice guidelines are often outdated, leading to underdiagnosis and ineffective treatment. Our aim was to identify microRNA (miRNA) biomarkers implicated in pathological mechanisms underlying these diseases. A comprehensive literature review using publicly accessible databases was conducted. Interesting miRNAs were extracted from relevant publications on ME/CFS and/or FM, and were then linked to pathophysiological processes possibly manifesting these chronic diseases. Dysregulated miRNAs in ME/CFS and FM may serve as promising biomarkers for these diseases. Key identified miRNAs, such as miR-29c, miR-99b, miR-128, miR-374b, and miR-766, were frequently mentioned for their roles in immune response, mitochondrial dysfunction, oxidative stress, and central sensitization, while miR-23a, miR-103, miR-152, and miR-320 were implicated in multiple crucial pathological processes for FM and/or ME/CFS. In summary, both ME/CFS and FM seem to share many dysregulated biological or molecular processes, which may contribute to their commonly shared symptoms. This miRNA-based approach offers new angles for discovering molecular markers urgently needed for early diagnosis or therapeutics to tackle the pathology of these medically unexplained chronic diseases.