Role of ERK in gender difference of fibromyalgia pain.

This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an acid-induced chronic widespread muscular pain model. We employed a twice acid-induced chronic musculoskeletal pain model in rats to evaluate mechanical pain behavior in both male and female groups. We further conducted protein analysis of dissected dorsal root ganglions from both genders. Both male and female rats exhibited a similar pain behavior trend, with females demonstrating a lower pain threshold. Protein analysis of the dorsal root ganglion (DRG) showed a significant increase in phosphorylated ERK after the second acid injection in all groups. However, phosphorylation of ERK was observed in the dorsal root ganglion, with higher levels in the male ipsilateral group compared to the female group. Moreover, there was a no difference between the left and right sides in males, whereas the significant difference was observed in females. In conclusions, the administration of acid injections induced painful behavior in rats, and concurrent with this, a significant upregulation of pERK was observed in the dorsal root ganglia, with a greater magnitude of increase in males than females, and in the contralateral side compared to the ipsilateral side. Our findings shed light on the peripheral mechanisms underlying chronic pain disorders and offer potential avenues for therapeutic intervention.

Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study.

AIMS: To develop a standardised, automated protocol for detecting protein gene product 9.5 (PGP9.5) positive intra-epidermal nerve fibres (IENFs) in skin biopsies, transitioning from the established manual technique to an automated platform. This automated method, although currently intended for research applications, may improve the accessibility of this diagnostic test for small fibre neuropathy in clinical settings. METHODS: Skin biopsies (n = 274) from 100 participants (fibromyalgia syndrome n = 62; idiopathic small fibre neuropathy: n = 16; healthy volunteers: n = 22) were processed using an automated immunohistochemistry platform. IENF quantification was performed by blinded examiners, with reliability assessed via a two-way mixed-effects model to evaluate inter- and intra-observer variability. RESULTS: The automated staining system reproduced intra-epidermal nerve fibre density (IENFD) counts consistent with free-floating sections (mean ± standard deviation: free-floating: 5.6 ± 3.4 fibres/mm; automated: 5.9 ± 3.2 fibres/mm). A median difference of 0.3 with a lower bound 95% Confidence Interval (CI) at -0.00005 established non-inferiority against a margin of -0.4 (p = .08). Specifically, the inter-class correlation coefficient (class denotes consistency in measured observations) was 99% (95% CI: 0.9-1), indicating excellent agreement between free-floating and automated methods. The inter- and intra-class coefficient between examiners were both 99% (95% CI: 0.9-0.1) for IENFD, demonstrating high reliability using sections stained using the automated method. INTERPRETATION: Automated immunohistochemistry provides high-throughput reliable and reproducible intra-epidermal nerve fibre quantification. This method, although currently proof-of-concept, for research use only, may be more widely deployed in histopathology laboratories to increase the adoption of IENFD assessment for the diagnosis of peripheral neuropathies.

Effect of neuronavigated repetitive Transcranial Magnetic Stimulation on pain, cognition and cortical excitability in fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome is a widespread chronic pain condition identified by body-wide pain, fatigue, cognitive fogginess, and sleep issues. In the past decade, repetitive transcranial magnetic stimulation has emerged as a potential management tool.. In the present study, we enquired whether repetitive transcranial magnetic stimulation could modify pain, corticomotor excitability, cognition, and sleep. METHODS: Study is a randomized, sham-controlled, double-blind, clinical trial; wherein after randomizing thirty-four fibromyalgia patients into active or sham therapy (n = 17 each), each participant received repetitive transcranial magnetic stimulation therapy. In active therapy was given at 1 Hz for 20 sessions were delivered on dorsolateral prefrontal cortex (1200 pulses, 150 pulses per train for 8 trains); while in sham therapy coil was placed at right angle to the scalp with same frequency. Functional magnetic resonance imaging was used to identify the therapeutic site. Pain intensity, corticomotor excitability, cognition, and sleep were examined before and after therapy. RESULTS: Baseline demographic and clinical parameters for both active and sham groups were comparable. In comparison to sham, active repetitive transcranial magnetic stimulation showed significant difference in pain intensity (P < 0.001, effect size = 0.29, large effect) after intervention. Other parameters of pain perception, cognition, and sleep quality also showed a significant improvement after the therapy in active therapy group only, as compared to sham. CONCLUSIONS: Findings suggest that repetitive transcranial magnetic stimulation intervention is effective in managing pain alongside cognition and sleep disturbances in patients of fibromyalgia. It may prove to be an important tool in relieving fibromyalgia-associated morbidity.

Pharmacological Treatment of Fibromyalgia Syndrome: A Practice-Based Review.

PURPOSE OF REVIEW: Fibromyalgia Syndrome (FMS) is a complex chronic pain condition characterized by widespread musculoskeletal pain and numerous other debilitating symptoms. The purpose of this review is to provide a comprehensive overview, based on everyday clinical practice, of the drugs presently employed in the treatment of FMS. RECENT FINDINGS: The treatment of FMS is based on a multimodal approach, with pharmacologic treatment being an essential pillar. The drugs used include tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, other antidepressants, anticonvulsants, myorelaxants, and analgesics. The effectiveness of these medications varies, and the choice of drug often depends on the specific symptoms presented by the patient. Many drugs tend to either address only some domains of the complex FMS symptomatology or have a limited effect on pain. Each treatment option comes with potential side effects and risks that necessitate careful consideration. It may be beneficial to divide patients into clinical subpopulations, such as FMS with comorbid depression, for more effective treatment. Despite the complexities and challenges, the pharmacological treatment remains a crucial part for the management of FMS. This review aims to guide clinicians in prescribing pharmacological treatment to individuals with FMS.

Effectiveness of balneotherapy in reducing pain, disability, and depression in patients with Fibromyalgia syndrome: a systematic review with meta-analysis.

Balneotherapy, using heated natural mineral waters at 36-38 °C, presents a comprehensive treatment approach for Fibromyalgia Syndrome (FMS). This study aims to assess the effect of balneotherapy in reducing pain intensity, disability, and depression in patients with FMS. We want to assess this effect at just four time-points: immediately at the end of the therapy, and at 1, 3, and 6 months of follow-up. Following PRISMA guidelines, we conducted an aggregate data meta-analysis, registered in PROSPERO CRD42023478206, searching PubMed Medline, Science Direct, CINAHL Complete, Scopus, and Web of Science until August 2023 for relevant randomized controlled trials (RCTs) that assess the effect of balneotherapy on pain intensity, disability, and depression in FMS patients. Methodological quality was assessed using the Cochrane methodology, and the pooled effect was calculated using Cohen's standardized mean difference (SMD) and its 95% confidence interval (95% CI) in a random-effects model. Sixteen RCTs were included in the meta-analysis. Balneotherapy is effective in reducing pain intensity (SMD - 1.67; 95% CI -2.18 to -1.16), disability (SMD - 1.1; 95% CI -1.46 to -0.7), and depression (SMD - 0.51; 95% CI -0.93 to -0.9) at the end of the intervention. This effect was maintained at 1, 3, and 6 months for pain intensity and disability. Balneotherapy improves both pain intensity and disability in patients with FMS, providing evidence that its positive effects are sustained for up to 6 months of follow-up. Nevertheless, it is important to note that the improvement in depression varies across different temporal phases.

Assessment of Temporal Somatosensory Discrimination in Females with Fibromyalgia: Reliability and Discriminative Ability of a New Assessment Tool.

We assessed the test-retest reliability and discriminative ability of a somatosensory temporal discrimination (SSTD) assessment tool for fibromyalgia syndrome (FMS) and determined if pain-related variables were associated with SSTD performance. Twenty-five women with FMS and twenty-five asymptomatic women were assessed during two sessions 7 to 10 days apart. The proportion of correct responses (range 0-100) was calculated. Sociodemographic information was collected for both groups. The participants with FMS also completed the widespread pain index and the Brief Pain Inventory. Test-retest reliability was verified by calculating intraclass correlation coefficients. Discriminative ability was verified by a between-group comparison of scores using a t-test. Associations between SSTD score and pain variables were tested using Pearson or Spearman correlation coefficients. The test-retest reliability of the SSTD score was excellent (ICC > 0.9, CI: 0.79-0.96) for the asymptomatic group and good for the FMS group (ICC: 0.81, 95% CI: 0.62-0.91). The median (Q1-Q3) test session SSTD score differed significantly between the FMS 84.1 (71-88) and the asymptomatic 91.6 (83.4-96.1) groups (p < 0.001). Only pain duration was associated with the SSTD score. In conclusion, the new SSTD test seems reliable for people with FMS and is discriminative. Further studies should examine its sensitivity to change and correlations with other SSTD tests.

Effect of prebiotic and probiotic supplementation on reduced pain in patients with fibromyalgia syndrome: a double-blind, placebo-controlled randomized clinical trial.

It has recently been observed that microorganisms in the gut can regulate brain processes through the gut microbiota-brain axis, affecting pain, depression, and sleep quality. Consequently, prebiotics and probiotics may potentially improve physical, psychological, and cognitive states in those with fibromyalgia syndrome (FMS) who have an altered microbiota balance. In a randomised, double-blind, placebo-controlled clinical trial to determine the effects of probiotic and prebiotic treatments on pain, sleep, quality of life, and psychological distress (depression and anxiety) in FMS, 53 female participants with FMS were randomised to receive either: 1) 4 × 1010 CFUs per day for the 18 patients in the probiotics group; 2) 10 g dose inulin per day for the 17 patients in the prebiotic group; or 3) a placebo for 8 weeks for the 18 patients in this group. The mean ages of the groups were similar and there was no significant difference between the groups. The impact of FMS on pain, sleep quality, quality of life, anxiety, and depressive symptoms were measured at baseline, 4 weeks, and 8 weeks post-intervention. Probiotic supplementation significantly decreased the Beck Depression Index (BDI), Beck Anxiety Index (BAI), and Pittsburgh Sleep Quality Index (PSQI) scores compared to baseline, while prebiotic supplementation only significantly decreased PSQI scores. Moreover, participants who received probiotic treatment presented a significantly reduced Visual Analogue Scale (VAS) score compared with those who received placebo treatment, after the interventions. Probiotic supplementation significantly improved sleep quality, depression, anxiety, and pain scores compared to those at baseline in FMS patients, while prebiotic supplementation significantly improved pain scores and sleep quality. The potential benefits of using probiotics for treatment management in FMS patients is supported by the results of the current study and might provide an important strategy to combat FMS-associated diseases.

Exploring the Overlooked Depression, Anxiety, Insomnia and Fibromyalgia Syndrome Burden in Arab Women with Type 2 Diabetes: New Avenues for Chronic Disease Management.

Background and Objectives: Although physical health is always studied for women with diabetes, the mental health aspect is generally overlooked for this chronic disease. The present study aimed to examine the prevalence of psychosomatic symptoms, namely, fibromyalgia syndrome, depression, anxiety, and insomnia, and how these symptoms related to the medications used in a cohort of women diagnosed with type 2 diabetes (DM) in Jordan. Materials and Methods: This cross-sectional study recruited women diagnosed with type 2 diabetes, and validated scales (PSRS, PHQ-9, GAD-7, and ISI-A) for fibromyalgia syndrome, depression, anxiety, and insomnia were used. The associations between the different medications used and the dependent variables were examined using four separate multivariate logistic regression models. Results: Data were analyzed from 213 participants. Of them, 27.2% met the threshold for fibromyalgia syndrome diagnosis, 38% met the threshold for severe depression, 36.2% met the threshold for severe anxiety, and 39.9% met the threshold for severe insomnia. Fibromyalgia syndrome symptoms were significantly associated with glimepiride (OR = 1.92, CI = 1.00-3.68), ß-blockers (OR = 2.21, CI = 1.03-4.70), diuretics (OR = 3.13, CI = 1.26-7.78), herbal remedies (OR = 2.12, CI = 0.98-4.55), and prescriptions for centrally acting medication (OR = 2.78, CI = 1.24-6.29). Significant associations were found between depression and diuretics (OR = 2.62, CI = 1.05-6.67), over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 3.49, CI = 1.69-7.23), and herbal remedies (OR = 5.07, CI = 2.40-10.69). In addition, anxiety was significantly related to diuretics (OR = 2.48, CI = 1.02-6.02), and OTC NSAIDs (OR = 2.60, CI = 1.29-5.21). Significant associations were evident between insomnia and ß-blockers (OR = 3.23, CI = 1.51-6.95), acetaminophen (OR = 2.09, CI = 1.06-4.08), NSAIDs (OR = 4.61, CI = 2.18-9.76), and herbal remedies (OR = 5.95, CI = 2.71-13.07). Conclusions: Medications are associated with high burden of fibromyalgia syndrome, depression, anxiety, and insomnia. These findings underscore the importance of revising and optimizing the pharmacotherapy of these vulnerable patients, performing close mental health monitoring and the implementation of non-pharmacological interventions by integrating mental health services for women with chronic diseases such as diabetes.

Fibromyalgia syndrome is associated with sexual dysfunction regardless of physical activity status: a cross-sectional study.

BACKGROUND: Fibromyalgia syndrome (FMS) is a rheumatic disorder that has been observed to affect self-perception of sexuality. AIM: The study aims to assess sexual dysfunction (SD), establish possible associations with SD levels, and evaluate the impact of physical activity (PA) levels on SD in Spanish women with FMS as compared with healthy control women. METHODS: The study was cross-sectional. A total of 170 women voluntarily agreed to participate between September 2019 and February 2020: 88 in the FMS group and 82 in the control group. OUTCOMES: The main outcome measures were SD, as assessed through the Female Sexual Function Index (FSFI), and PA levels, as assessed with a structured interview. RESULTS: There were significant differences in every domain and total SD score between the FMS and control groups (P < .05). In addition, we obtained a moderate significant direct association (χ2[1] = 37.071, P < .05, phi = 0.467) when exploring the associations between FMS and risk of SD. Results showed statistically significant differences between the FMS group and the control group when PA levels were not reached in the desire, pain, and total scores of the FSFI (P < .05). When the PA levels were reached, between-group differences were found in all domains, as well as in the total score of the FSFI (P < .05). CLINICAL IMPLICATIONS: Sexual function should be evaluated in women with FMS, while future treatments should address this clinical area with the aim of managing SD in this population. STRENGTHS AND LIMITATIONS: The main limitation is that the outcome measures were self-reported. CONCLUSION: We found a high prevalence of SD in Spanish women with FMS, with an impact on aspects such as desire, arousal, lubrication, orgasm, satisfaction, and pain during sexual intercourse. In addition, there is a moderate direct association between FMS and SD. Ultimately, the results showed that, irrespective of PA, women with FMS reported increased SD.

The impact of fibromyalgia syndrome on obstructive sleep apnea syndrome in terms of pain threshold, daytime symptoms, anxiety, depression, disease severity, and sleep quality: a polysomnographic study.

BACKGROUND: Current studies have focused on the association of fibromyalgia syndrome (FMS) and obsctructive sleep apnea syndrome (OSAS). Results of these studies on the effect of this association have been inconsistent. The current study aimed to investigate the effect of FMS on OSAS regarding sleep quality, pressure pain threshold, fatigue, daytime symptoms, anxiety, and depression, and also to determine the relationship between OSAS severity and FMS. METHODS: In a cross-sectional design, patients diagnosed with OSAS were evaluated in two groups comparing those with and those without FMS. Data on demographics, headache, morning fatigue, and chronic pain duration were collected. Questionnaires including the Fatigue Severity Scale (FSS), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were completed. Pressure pain threshold, tender points, and polysomnographic data were recorded. RESULTS: Of 69 patients, 27 were diagnosed with FMS + OSAS and 42 were diagnosed as OSAS only. Statistically significant differences were found between the two groups in VAS, pain duration, morning fatigue, headache, BAI, tender point count, FIQ and FSS scores, and algometer measurements. All polysomnografic data were compared, and no statistically significant differences were found between the two groups. There were no statistically significant differences in the algometer, BDI, BAI, FIQ, and FSS scores when analyzed according to the severity of OSAS. CONCLUSION: The findings suggest that FMS has no effect on polysomnographic parameters of OSAS. Headache, daytime fatigue, anxiety, depression, pain duration, and pain intensity are higher while the pressure pain threshold is lower when FMS is present. No correlation was found between OSAS severity and FMS, fatigue, pressure pain threshold, depression, and anxiety. CLINICAL TRIAL REGISTRATION NUMBER: NCT05367167/date: April 8, 2022.

Prevalence of fibromyalgia syndrome in Saudi Arabia: a systematic review and meta-analysis.

BACKGROUND: The current systematic review and meta-analysis was conducted to estimate the prevalence of fibromyalgia syndrome (FMS) in Saudi Arabia. METHODS: A PRISMA systematic search appraisal and meta-analysis were conducted. A systematic literature search of English publications in PubMed, Embase, PsycINFO, Web of Science, MEDLINE, and Google Scholar, was conducted up to December 2022. Generic, methodological and statistical data was extracted from the eligible studies. Meta-analysis was done using Comprehensive Meta-Analysis Software. The effect size estimates were calculated using the Fail-Safe N test. The funnel plot, Begg's and Mazumdar's rank correlation tests were employed to find any potential bias. The strength of the association between two variables is assessed using Kendall's tau. A fixed-effects model for the meta-analysis. RESULTS: The literature search yielded a total of 2479 studies. Eight papers were included in the final analysis with sample size ranging 40 to 1686. All studies were cross-sectional except two, which were retrospective. The total number of the participants recruited in the included articles was 4967 (1794 males and 3173 females); with age ranged between 20 and 79 years. There was high heterogeneity among studies articles (Q = 270.187; p-value 0.001); the tau value was 0.179. The pooled event rates and the 95% confidence intervals (CIs) for the prevalence of FMS in Saudi Arabia in a fixed-effects model was 13.4% (95% CI: 0.124-0.144). CONCLUSION: Our results clearly demonstrate that FMS is highly prevalent (13.4%) in Saudi Arabia. It also more common among women. The high prevalence of FMS in Saudi Arabia should be seriously considered and planners should take steps to reduce it.

Psychological characteristics of juvenile fibromyalgia syndrome.

BACKGROUND: The aim of the study was to compare psychological characteristics of adolescent patients with juvenile fibromyalgia syndrome (JFM) with individuals suffering from chronic pain (CP) due to headache or joint pain in the lower limbs unrelated to oncological, inflammatory or autoimmune diseases. METHODS: The study was conducted on 37 patients aged 13-18 years old, monitored at the Pain Therapy Outpatient Clinic of the "Bambino Gesù" Pediatric Hospital in Rome. A total of 21 patients were suffering from CP (headache and recurrent arthralgia) and 16 from JFM, diagnosed according to the criteria of the American College of Rheumatology. All subjects were evaluated by a pain therapy specialist, a rheumatologist and a clinical psychologist for the following psycho-emotional areas and/ or characteristics: cognitive abilities, attention, memory, learning, alexithymia, somatisation, anxiety, depression, coping skills. A clinical psychologist interviewed all patients to assess school absences, the use of analgesic medication, the presence of sleep disorders (e.g., nonrestorative sleep) and the intensity of perceived pain. RESULTS: Similarities emerged between the two groups in the presence of depression, anxiety, somatisation, alexithymia, school absenteeism, medication use and reported pain level. The peculiar characteristics of the JFM group, which emerged from our pilot study, were the higher prevalence of the illness amongst women, a higher incidence of sleep disturbances, and a better cognitive endowment, despite some attention and mnemonic deficiencies. CONCLUSIONS: To conclude, the present study suggests that the clinical and psychological characteristics of JFM appear to be similar to those found in the CP population.

Investigation of the dual-task performance and affecting factors in female patients with fibromyalgia syndrome.

Recent studies report that dual-task (DT) performance might be affected in patients with fibromyalgia syndrome (FMS). This cross-sectional study aims to compare the DT performance in female patients with FMS and healthy controls, and to investigate the DT-related factors in these patients. This study was conducted at a university hospital between November 2021 and April 2022. Forty females aged 30-65, diagnosed with FMS, and 40 aged-matched pain-free healthy controls were included. All participants performed the Timed Up and Go Test under a single task (ST) and a cognitive DT condition, and the DT cost was calculated. The following evaluations were applied; The six-minute walk test, Baecke Habitual Physical Activity Questionnaire, Multidimensional Fatigue Inventory-20, Toronto Alexithymia Scale, Trail Making Test, and the Revised Fibromyalgia Impact Questionnaire. As a result of the study, the patient group showed lower performance than controls in both, ST and DT conditions (p < .05). Disease duration, pain and fatigue severity, functional capacity, leisure time and physical activity total scores, alexithymia scores, health status, and cognitive variables were correlated with DT performance in the patient group (p < .05). According to our results, we consider that the rehabilitation approach for females with FMS should take into account DT and related characteristics.

The preventive role of vitamin D in the prevention and management of Fibromyalgia syndrome.

Aim: Vitamin D deficiency is a prevalent condition among the general population, all around the world. Vitamin D deficiency is defined as serum levels of 25-hydroxy vitamin D lower than 20 ng/ml (50 nmol/ml). It is a known actor in the skeletal system through the regulation of calcium and phosphate metabolism and bone mineralization. Still, the role of vitamin D as an immunomodulator is yet to be acknowledged by healthcare practitioners as a cause, precipitating factor, and contributor to a variety of diseases. Vitamin D is shown to be an actor in multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus, and irritable bowel syndrome. Fibromyalgia syndrome (FMS) is a chronic disorder associated with a severe pain that can affect a patient's musculoskeletal system, daily routine, and mood. The clinical presentation encapsulates other disorders such as lethargy and sleep problems, brain fog and other cognitive issues, and physical and psychiatric symptoms. Methods: We have used PubMed and ResearchGate in the reviewing process of our paper. We tried to address as many topics as we judged to be adequate and relevant for the practicing clinicians. Results: Management of fibromyalgia syndrome is both nonpharmacologic and pharmacologic, which are provided in a stepwise fashion. Yet, the management of FMS remains a challenge, heeding a multidisciplinary approach. Among the dietary interventions, we chose vitamin D and its effects on FMS. Literature shows that supplementation improves pain caused by fibromyalgia syndrome, yet specific recommendations are still to be created. Conclusions: We call on all the relevant governmental bodies, public health experts and health policy makers, healthcare practitioners, and the civil society to use novel data related to fibromyalgia syndrome, and in a broader perspective, the integral role of vitamin D.

ASSESSMENT OF THE ASSOCIATION OF SEROTONIN TRANSPORTER GENE (5-HTTVNTR & 5-HTTLPR) POLYMORPHISM IN PATIENTS WITH FIBROMYALGIA SYNDROME.

OBJECTIVE: The aim: To study the clinical and the genetic association of 5-HTTVNTR and the 5-HTTLPR polymorphisms in women with FMS. PATIENTS AND METHODS: Materials and methods: 105 FMS patients and 105 controls were enrolled in the study. Polymerase chain method was used to analyse the 5-HTTLPR & 5-HTTVNTR gene polymorphism. The psychopathology status of the 105 FMS patients and 105 healthy controls was assessed using the Beck Depression Inventory (BDI) and the Symptom Checklist-90-Revised (SCL-90-R) questionnaires. RESULTS: Results: In FMS patients and controls, the 10/10, 10/12, and 12/12 genotypes of the 5-HTTVNTR polymorphism were found in 3.8% and 2.9%, 20% and 15.2%, and 76.28% and 81.90%, respectively. Additionally, the L/L, S/L, and S/S genotypes of the 5-HTTLPR polymorphism were found in 4.8% and 2.9%, 36.2% and 40%, 59% and 57.1%, in FMS patients and healthy controls, respectively. There were no significant differences in the frequency of genotypes between FMS patients and controls. There were no significant differences in the BDI and the SCL-90-R scores according to the serotonin transporter genotypes. CONCLUSION: Conclusions: We found no significant difference between 5-HTT gene polymorphism (5-HTTVNTR and 5-HTTLPR) and the psychiatric test results (P>0.05) in FMS patients. Hence, we conclude that serotonin gene polymorphism (5-HTTLPR & 5-HTTVNTR) is not associated with FMS in north Indian women. Our results suggests that the serotonin transporter polymorphism does not seem to be a susceptibility factor for FMS.

Can the monocyte-to-HDL ratio be used as an inflammation marker in patients with fibromyalgia syndrome?

Background and Aim: The monocyte-to-high-density lipoprotein (HDL) ratio (MHR) may be used as a marker of inflammation and oxidative stress. This study aimed to evaluate the use of MHR and platelet markers in patients with fibromyalgia syndrome (FMS) and demonstrate MHR's relationship with inflammation, the Fibromyalgia Impact Questionnaire (FIQ), and quality of life. Materials and Methods: Ninety FMS patients and 90 healthy controls, whose clinical and laboratory evaluations were performed simultaneously, were included in the study. The monocyte, platelet, HDL, MHR, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), mean platelet volume (MPV), and platelet distribution width (PDW) values of all patients were evaluated. The quality of life of the participants was assessed using the FIQ and their general health using the health assessment questionnaire (HAQ). Results: Age, body mass index (BMI), and marital status distribution were similar in both groups. The FMS patients had a mean disease duration of 11.29 ± 2.62 months. The median monocyte, platelet, MPV, visual analog scale (VAS), FIQ, and HAQ values and the mean MHR of the FMS patients were significantly higher than the control group, while the mean HDL level was significantly lower (P < 0.05). There was a weak negative correlation between the MPV and HAQ score and the PDW and HAQ score (rs = -0.225, P = 0.042 and rs = -0.249, P = 0.024, respectively), whereas no correlation was detected between the MHR and the FIQ and HAQ scores in FMS patients. According to the receiver operating characteristic curve analysis, MHR had prediction of FMS (P = 0.002; sensitivity = 0.63, specificity = 0.50, cut-off point ≥8.4). Conclusions: Our results suggest that the monocyte, platelet, HDL, MHR, and MPV parameters can be used in the evaluation of inflammation in FMS patients.

Oxytocin inhibits hindpaw hyperalgesia induced by orofacial inflammation combined with stress.

Oxytocin (OT) is recognized as a critical neuropeptide in pain-related disorders. Chronic pain caused by the comorbidity of temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) is common, but whether OT plays an analgesic role in the comorbidity of TMD and FMS is unknown. Female rats with masseter muscle inflammation combined with 3-day forced swim (FS) stress developed somatic hypersensitivity, which modeled the comorbidity of TMD and FMS. Using this model, the effects of spinal OT administration on mechanical allodynia and thermal hyperalgesia in hindpaws were examined. Furthermore, the protein levels of OT receptors and 5-HT2A receptors in the L4-L5 spinal dorsal horn were analyzed by Western blot. The OT receptor antagonist atosiban and 5-HT2A receptor antagonist ritanserin were intrathecally injected prior to OT injection in the separate groups. Intrathecal injection of 0.125 µg and 0.5 µg OT attenuated the hindpaw hyperalgesia. The expression of OT receptors and 5-HT2A receptors in the L4-L5 spinal dorsal horn significantly increased following intrathecal injection of 0.5 µg OT. Intrathecal administration of either the OT receptor antagonist atosiban or 5-HT2A receptor antagonist ritanserin blocked the analgesic effect of OT. These results suggest that OT may inhibit hindpaw hyperalgesia evoked by orofacial inflammation combined with stress through OT receptors and/or 5-HT2A receptors, thus providing a therapeutic prospect for drugs targeting the OT system and for patients with comorbidity of TMD and FMS.

Relevance of Religiosity for Coping Strategies and Disability in Patients with Fibromyalgia Syndrome.

Coping strategies are essential for the outcome of chronic pain. This study evaluated religiosity in a cohort of patients with fibromyalgia syndrome (FMS), its effect on pain and other symptoms, on coping and FMS-related disability. A total of 102 FMS patients were recruited who filled in questionnaires, a subgroup of 42 patients participated in a face-to-face interview, and data were evaluated by correlation and regression analyses. Few patients were traditionally religious, but the majority believed in a higher existence and described their spirituality as "transcendence conviction". The coping strategy "praying-hoping" and the ASP dimension "religious orientation" (r = 0.5, P < 0.05) showed a significant relationship independent of the grade of religiosity (P < 0.05). A high grade of belief in a higher existence was negatively associated with the choice of ignoring as coping strategy (r = - 0.4, P < 0.05). Mood and affect-related variables had the highest impact on disability (b = 0.5, P < 0.05). In this cohort, the grade of religiosity played a role in the choice of coping strategies, but had no effects on health and mood outcome.

UNRAVELING THE CLINICO-GENETIC ASSOCIATION OF CATECHOL-O-METHYLTRANSFERASE-RS4680 G>A GENE POLYMORPHISM IN WOMEN WITH FIBROMYALGIA SYNDROME.

OBJECTIVE: The aim: To determine the clinical and the genetic association of the COMT rs4680 SNP in women with FMS. PATIENTS AND METHODS: Materials and methods: Extracted DNA from peripheral blood samples were utilized as template for the PCR and RFLP analysis. RESULTS: Results: A significant difference was found in the distribution of the COMT genotype between FMS patients and controls (P<0.05). The frequency of GG, AG, AA genotypes were 12%, 72%, 21% in FMS patients and 32%, 62%, 11% in controls. The clinical features of FMS reveal that FIQR and the severity of pain measured by VAS were significantly associated with the COMT rs4680 SNP (P=0.042; P=0.016). The co-dominant model for GG verse v. AG genotype (P=0.004) and AG v. AA genotype (P=0.002) has shown to be high risk for FMS. An increased risk of FMS in the dominant model for (AG+AA) v. GG genotype (P=0.001) and no significant difference was found between (GG+AG) v. AA genotype (P=0.08) in the recessive model. The result indicated that A allele considerably increase the risk of FMS (P=0.004) in comparison to the G allele. CONCLUSION: Conclusions: AA genotype and A allele of the COMT rs4680 SNP were significantly associated with severity in FMS patients and also plays a significant role in the clinical manifestation of this disease.

Acetyl-L-carnitine in chronic pain: A narrative review.

Acetyl-L-carnitine (ALC) is an endogenous molecule that not only plays a role in energy metabolism, but also has antioxidant properties, protects from oxidative stress, modulates brain neurotransmitters such as acetylcholine, serotonin and dopamine, and acts on neurotrophic factors such as nerve growth factor (NGF) and metabotropic glutamate (mGlu) receptors by means of epigenetic mechanisms. Importantly, it induces mGlu2 expression at nerve terminals, thus giving rise to analgesia and preventing spinal sensitisation. It has also been found to have even long-term neurotrophic and analgesic activity in experimental models of chronic inflammatory and neuropathic pain. The aim of this narrative review is to summarise the current evidence regarding the use of ALC in patients with chronic pain, and cognitive and mood disorders, and investigate the rationale underlying its use in patients with fibromyalgia syndrome, which is characterised by nociplastic changes that increase the sensitivity of the nervous system to pain.