Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis.

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)-converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.

Mitochondrial structural alterations in fibromyalgia: a pilot electron microscopy study.

OBJECTIVES: The pathogenesis of fibromyalgia (FM), characterised by chronic widespread pain and fatigue, remains notoriously elusive, hampering attempts to develop disease modifying treatments. Mitochondria are the headquarters of cellular energy metabolism, and their malfunction has been proposed to contribute to both FM and chronic fatigue. Thus, the aim of the current pilot study, was to detect structural changes in mitochondria of peripheral blood mononuclear cells (PBMCs) of FM patients, using transmission electron microscopy (TEM). METHODS: To detect structural mitochondrial alterations in FM, we analysed PBMCs from seven patients and seven healthy controls, using TEM. Patients were recruited from a specialised Fibromyalgia Clinic at a tertiary medical centre. After providing informed consent, participants completed questionnaires including the widespread pain index (WPI), symptoms severity score (SSS), fibromyalgia impact questionnaire (FIQ), beck depression inventory (BDI), and visual analogue scale (VAS), to verify a diagnosis of FM according to ACR criteria. Subsequently, blood samples were drawn and PBMCs were collected for EM analysis. RESULTS: TEM analysis of PBMCs showed several distinct mitochondrial cristae patterns, including total loss of cristae in FM patients. The number of mitochondria with intact cristae morphology was reduced in FM patients and the percentage of mitochondria that completely lacked cristae was increased. These results correlated with the WPI severity. Moreover, in the FM patient samples we observed a high percentage of cells containing electron dense aggregates, which are possibly ribosome aggregates. Cristae loss and possible ribosome aggregation were intercorrelated, and thus may represent reactions to a shared cellular stress condition. The changes in mitochondrial morphology suggest that mitochondrial dysfunction, resulting in inefficient oxidative phosphorylation and ATP production, metabolic and redox disorders, and increased reactive oxygen species (ROS) levels, may play a pathogenetic role in FM. CONCLUSIONS: We describe novel morphological changes in mitochondria of FM patients, including loss of mitochondrial cristae. While these observations cannot determine whether the changes are pathogenetic or represent an epiphenomenon, they highlight the possibility that mitochondrial malfunction may play a causative role in the cascade of events leading to chronic pain and fatigue in FM. Moreover, the results offer the possibility of utilising changes in mitochondrial morphology as an objective biomarker in FM. Further understanding the connection between FM and dysfunction of mitochondria physiology, may assist in developing both novel diagnostic tools as well as specific treatments for FM, such as approaches to improve/strengthen mitochondria function.

CD55-deficiency in Jews of Bukharan descent is caused by the Cromer blood type Dr(a-) variant.

The complement system regulator CD55 was initially found to carry the Cromer blood group system antigens, and its complete loss of function was subsequently revealed to cause a severe monogenic gastrointestinal syndrome characterized by protein-losing enteropathy and susceptibility to venous thrombosis. Here we present homozygosity to the CD55 c.596C>T; p.Ser199Leu variant, which was previously described as the Cromer Dr(a-) genotype, in two Bukharan Jewish CD55-deficiency patients with variable disease severity. We confirm that this missense variant causes aberrant splicing and deletion of 44 bp in exon 5, leading to premature termination and low expression of the CD55 protein. Furthermore, Patient 1 exhibited a mildly abnormal B cell immunophenotyping profile. By population screening we established that this variant is highly prevalent in the Bukharan Jewish population, with a carrier frequency of 1:17, suggesting that many similar patients are un- or mis-diagnosed. The phenotypic variability, ranging from abdominal pain when eating a high-fat diet to the full CD55-deficiency phenotype, is likely related to modifiers affecting the proportion of the variant that is able to escape aberrant splicing. Establishing the diagnosis of CD55-deficiency in a timely manner, even in patients with milder symptoms, may have a critical effect on their management and quality-of-life since treatment with the complement inhibitor eculizumab is highly effective in ameliorating disease manifestations. Awareness of founder mutations within certain populations can further guide genetic testing and prevent a diagnostic odyssey, by placing this CD55 variant high on the differential diagnosis.

The Montreal Cognitive Assessment Test (MoCA) as a screening tool for cognitive dysfunction in fibromyalgia.

OBJECTIVES: Cognitive dysfunction is one of the criteria for the diagnosis of fibromyalgia (FM) and is typically based on self-report questionnaires such as the Symptom Severity Scale. However, recent studies have shown that there is no correlation between these subjective measures of cognitive dysfunction and more lengthy objective measures of cognitive functioning. This points to the need for a briefer valid evaluation tool for cognitive dysfunction in FM. The aim of this study is to examine whether the Montreal Cognitive Assessment (MoCA) test is a valid measure of cognitive assessment in FM patients, by comparing it to a comprehensive computerised cognitive assessment battery. METHODS: Sixty-two FM patients (55 women, 7 men, mean age = 46.17 years, sd=12.56) were administered the MoCA and a computerised cognitive assessment battery. FM symptoms were assessed on the Fibromyalgia Impact Questionnaire (FIQ), the Widespread Pain Index (WPI), the Symptom Severity Scale (SSS), and the Beck Depression Inventory (BDI-2). Patient effort was controlled on the TOMM (Test of Memory Malingering). RESULTS: Moderate positive correlations were found between the MoCA and the computerised cognitive scores as follows: Global Cognitive Score (r=0.493**, p=0.00), Memory Index Score (r= 0.384**, p=0.002), Executive Function Index Score (r=0.461**, p=0.00), Attention Index Score (r=0.310*, p=0.016), Information Processing Speed Index Score (r=0.435**, p=0.001), and Motor Skills (r=0.406**, p=0.002). CONCLUSIONS: The MoCA is an acceptable cognitive screening test for the cognitive evaluation of FM patients.

Fibromyalgia: one year in review 2022.

Fibromyalgia syndrome (FM) is a chronic widespread pain syndrome characterised by fatigue, sleep disturbances and many idiopathic pain symptoms. The aim of this review is to describe and summarise the most recent findings concerning the diagnosis, aetiopathogenesis and treatment of fibromyalgia syndrome published between January 2021 and January 2022 and appearing on PubMed database. In particular, last year's literature focused on the impact of COVID-19 pandemic on FM patients, on new aetiopathogenetic horizons and the last conclusions about pharmacological and non-pharmacological interventions.

Elevated Serum Amyloid A Levels Contribute to Increased Platelet Adhesion in COVID-19 Patients.

Coronavirus disease-19 (COVID-19) patients are prone to thrombotic complications that may increase morbidity and mortality. These complications are thought to be driven by endothelial activation and tissue damage promoted by the systemic hyperinflammation associated with COVID-19. However, the exact mechanisms contributing to these complications are still unknown. To identify additional mechanisms contributing to the aberrant clotting observed in COVID-19 patients, we analyzed platelets from COVID-19 patients compared to those from controls using mass spectrometry. We identified increased serum amyloid A (SAA) levels, an acute-phase protein, on COVID-19 patients' platelets. In addition, using an in vitro adhesion assay, we showed that healthy platelets adhered more strongly to wells coated with COVID-19 patient serum than to wells coated with control serum. Furthermore, inhibitors of integrin aIIbß3 receptors, a mediator of platelet-SAA binding, reduced platelet adhesion to recombinant SAA and to wells coated with COVID-19 patient serum. Our results suggest that SAA may contribute to the increased platelet adhesion observed in serum from COVID-19 patients. Thus, reducing SAA levels by decreasing inflammation or inhibiting SAA platelet-binding activity might be a valid approach to abrogate COVID-19-associated thrombotic complications.

Physical and mental impact of COVID-19 outbreak on fibromyalgia patients.

OBJECTIVES: Acute or chronic stress may trigger or aggravate symptoms of fibromyalgia (FM). We aimed to evaluate the physical and mental health of fibromyalgia patients during the COVID 19 outbreak and identify protective/risk factors. METHODS: An online survey was published in May 2020, following two months of lockdown due to the COVID 19 outbreak, including questionnaires regarding demographic characteristics, access to medical services, anxiety, depression, life approach, coping strategies, perception of social support, widespread pain index (WPI) and symptoms severity scale (SSS), insomnia severity index (ISI) and patient global assessment. RESULTS: Of the 233 patients included in the study, 98% were forced to discontinue complementary or alternative treatments during lockdown. Up to 30% of responders who had been treated with medical cannabis had to stop due to logistic difficulties and this was associated with significantly higher scores of WPI/SSS (p=0.024). Higher levels of anxiety and depression were significantly correlated with higher levels of pain, sleep disorders and subjective perception of deterioration (p=0.00). Higher scores of social support and positive life approach were correlated with less anxiety and depression (p<0.01), lower levels of pain (p<0.05) and less sleep disturbances (p<0.01). Avoidant coping style was strongly associated to higher levels of pain, sleep disturbances, anxiety, depression, and subjective perception of worsening (p<0.01). CONCLUSIONS: Fibromyalgia patients reported adverse mental and physical outcomes during the COVID-19 outbreak. Factors such as stopping current treatments may play a central role. Social support and a positive life approach appear to be protective.

A modified version of the 2016 ACR fibromyalgia criteria cognitive items results in stronger correlations between subjective and objective measures of cognitive impairment.

OBJECTIVES: In a previous study, we showed that the subjective item assessing cognitive impairment (SSS-Cog) for fibromyalgia (FM) did not correlate with the objective cognitive measures. In the current study, we describe two modifications designed to enhance this correlation: extending the SSS-cog scale from 0-3 to 1-5, and administration of a new questionnaire that specifically targets the cognitive impairments associated with FM. METHODS: Sixty-two FM patients underwent a computerised cognitive assessment battery. FM symptoms were assessed on the Fibromyalgia Impact Questionnaire (FIQ); the Widespread Pain Index (WPI); the Symptom Severity Scale (SSS), the new SSS-Cog scale ranging from 1 to 5, the Beck Depression Inventory (BDI) and the new cognitive questionnaire developed by the authors. RESULTS: Significant correlations were found between the new SSS-Cog, the global cognitive score and all indices [Global Score r=-0.532, p=0.00; Indices: Memory r=-0.305, p=.01; Executive function r=-0.514, p=0.00; Attention r=-0.471, p=0.00; Processing Speed r=-0.468, p=0.00; Motor Skills r=-0.495, p=.00]. Significant correlations were found between the new questionnaire and the global cognitive score and all indices except the memory index [Global Score r=-0.522, p=0.00; Indices: Memory r=-0.163, p=0.212; Executive function r=-0.477, p=0.00; Attention r=-0.439, p=0.00; Processing Speed r=-0.496, p=0.00; Motor Skills r=-0.532, p=0.00]. CONCLUSIONS: Given the simplicity involved in extending the scale, we suggest incorporating this modification into the FM diagnostic criteria of the American College of Rheumatology (ACR).

Relationship between religiosity, spirituality and physical and mental outcomes in fibromyalgia patients.

OBJECTIVES: The coping mechanisms utilised by patients with the fibromyalgia syndrome (FM) pose a crucial focus of treatment. Previous research points to the positive effects of religiosity and spirituality (R/S) as tools for coping with illness. The role of these factors in coping with chronic pain in FM has not previously been studied. The aim of this study was to evaluate the link between R/S and FM outcomes. METHODS: Fifty-five FM patients (ACR criteria) attending a tertiary rheumatology clinic completed a packet of questionnaires assessing demographic data, levels of religiosity and spirituality (SpREUK) and locus of control (LOC). These variables were then individually assessed for influence on FM outcome measures, using the Fibromyalgia Impact Questionnaire (FIQ), the SF-36, and the Beck Depression Index (BDI). RESULTS: A high score on SpREUK I (search for meaningful support) was negatively correlated with the Role-Physical (p=0.032) and Role-Emotional (p<0.005) scales on SF-36. Secular patients scored higher on SF-36 domains of "Role limitation due to emotional health" and "General health" (p<0.05). Employment demonstrated a positive correlation with the FIQ (p<0.01), the BDI (p<0.001), and the SF-36 (p<0.05). Physical activity correlated positively with BDI scores (p=0.012) and better scores on SF-36: energy/fatigue (p=0.024), social-functioning (p=0.014) and physical-functioning (p<0.01). No significant correlation was found between LOC (internal versus external) and FM outcomes. No significant correlation was found between SpREUK domains and the BDI. CONCLUSIONS: FM patients do not appear to benefit from high levels of R/S. Physicians should be aware of the impact of R/S on well-being in this population.

Pain and transition: evaluating fibromyalgia in transgender individuals.

OBJECTIVES: As members of a gender minority, transgender individuals face many challenges. Many experience distress, depression, anxiety and suicidal ideation related to gender non-conformity and transphobia. Stress and trauma may contribute to the development of fibromyalgia (FM) syndrome, characterised by widespread pain and fatigue. The prevalence of FM among transgenders is not known. METHODS: Transgender participants were recruited at a specialised clinic. Questionnaires included the Widespread Pain Index (WPI), the Symptom Severity Score (SSS) and the SF-36. Data concerning hormonal treatment protocols was retrieved from charts. The current prevalence of FM was determined, as well as the prevalence before and after testosterone treatment among TM. Pearson correlations were calculated between all measures. RESULTS: 115 participants were recruited, 62.6% transgender men (TM), 37.4% transgender women (TW). 17 individuals (14.8%) fulfilled the 2011 modified ACR FM criteria, for a rate of 19.4% among TM and 6.98% among TW. Among TM, FM was associated with younger age, smoking and SF-36 sub-scales related to physical functioning, role limitation due to physical pain, fatigue, pain and general health. Among TW, FM was associated with social status, employment, depression, existing medical treatment and substance abuse, as well as SF-36 subscales related to role limitations affected due to pain. CONCLUSIONS: Fibromyalgia symptoms are highly prevalent among Israeli transgender individuals and may be related to psychological distress and gender dysphoria. Healthcare professionals treating transgenders should remain vigilant for the occurrence of chronic pain, fatigue and other FM-related symptoms and be prepared to treat and/or refer such patients accordingly.

Good pain, bad pain: illness perception and physician attitudes towards rheumatoid arthritis and fibromyalgia patients.

OBJECTIVES: Rheumatoid arthritis (RA) and fibromyalgia syndrome (FM) are common diagnoses encountered in rheumatology practice, but do not enjoy the same status. We aimed to examine physician's illness perceptions regarding these two rheumatologic disorders and to evaluate how they correlate with their relationship with these patients. METHODS: Forty-five rheumatologists were enrolled in the study. Demographic data were registered. Measures collected included the Brief Illness Perception Questionnaire (BIPQ) and the Difficult Doctor- Patient Relation Questionnaire (DDPRQ-10). Both were recorded twice, related to FM and RA. Empathy and burnout were also assessed. RESULTS: Of 45 physicians included in the study, only 53% were willing to accept FM patients. FM was considered a more severe disease than RA (FM-BIPQ mean score 54, SD 5.5 versus RA-BIPQ mean 45.6 SD 6.5, p<0.00) in terms of treatment control, understanding and emotional response generated by the disease. Doctor-patient relationship was perceived more difficult with FM patients compared to RA patients (FM-DDPRQ mean score 35.1, SD 9.2 versus RA-DDPRQ mean 19.6, SD 7.1, p<0.00), and was significantly correlated to the patient's concern about the illness (p<0.034) and patient's emotional response (p<0.036). Resistance to accept FM patients was largely influenced by difficult doctor-patient relationship. Higher levels of empathy were found in physicians experiencing less difficulty with FM patients. CONCLUSIONS: FM patients were perceived as more difficult than RA patients, with a high level of concern and emotional response. A high proportion of physicians were reluctant to accept them because they feel emotional/psychological difficulties meeting and coping with these patients.

Diagnostic and therapeutic care pathway for fibromyalgia.

Early diagnosis and timely and appropriate treatments positively influence the history of fibromyalgia syndrome (FM), with favourable repercussions at clinical, psychological, social and economic levels. Notwithstanding, there are still significant problems with timeliness of diagnosis, access to pharmacological therapies - particularly to innovative ones - and appropriate and effective taking in charge of patients. All the aforementioned factors have a great impact on FM patients' quality of life. Indeed, even though the World Health Organisation recognised FM as a chronic condition in the International Classification of Diseases 10th edition (ICD-10), many countries still fail to recognise the syndrome, and this negatively influences the capability to appropriately protect and care for patients. This is the case in several European Countries. In Italy, a few Regions have started to put in place precise indications for people suffering from FM, aiming at the implementation of diagnostic-therapeutic pathways. The Diagnostic-Therapeutic Care Pathway (DTCP) provides an important tool to meet the needs of patients suffering from chronic diseases. They present the organisation of an integrated assistance network. This includes a seamless path for disease prevention, diagnosis and treatment, by means of cooperation among physicians and other healthcare professionals.

Fibromyalgia position paper.

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.

Diagnosis of fibromyalgia: comparison of the 2011/2016 ACR and AAPT criteria and validation of the modified Fibromyalgia Assessment Status.

OBJECTIVE: To compare the concordance of the three diagnostic criteria, respectively the 2011 ACR criteria (ACR 2011 Cr), the ACR 2016 criteria (ACR 2016 Cr) and the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION)-APS Pain Taxonomy criteria (AAPT Cr), and to explore the performance of an additional set of criteria, the modified Fibromyalgia Assessment Status (FAS 2019 modCr), in the diagnosis of FM syndrome. METHODS: Consecutive patients with chronic widespread pain, referred by the primary care setting, underwent rheumatologic assessment that established the presence or not of FM and were investigated through the four sets of proposed criteria. For the FAS 2019 modCr, discriminant validity to distinguish patients with FM and non-FM was assessed with receiver operating characteristic curve analysis. RESULTS: A total of 732 (405 with FM and 327 with other common chronic pain problems) patients were evaluated. Against the clinical diagnosis of FM, the sensitivity, specificity and correct classification were, respectively: 79.8, 91.7 and 85.1% for ACR 2011 Cr; 78, 90.5 and 83.6% for the ACR 2016 Cr; and 73.8, 91.7 and 81.8% for the AAPT Cr. The alternative set, proposed on the FAS 2019 modCr, provided a maximal diagnostic accuracy with a score ≥20 (Youden's index), with a sensitivity of 84.2%, specificity 89.0% and positive likelihood ratio 7.65. CONCLUSION: There is a considerable agreement between criteria-based diagnoses of FM, although the AAPT Cr perform least well in terms of percentage of correct classification. The FAS 2019 modCr had comparable characteristics.

High prevalence of fibromyalgia among Israeli school teachers.

OBJECTIVES: Fibromyalgia syndrome (FM), characterised by widespread pain and fatigue, has frequently been associated with stress in various models, including workplace related stress. In the current study we have evaluated the prevalence of FM symptoms among Israeli school teachers and have attempted to correlate such symptoms with work-related stress. METHODS: Individuals, all currently employed as school teachers in Israel, were recruited to the study. Participants were asked to answer a questionnaire evaluating symptoms of FM, based on the current diagnostic criteria, which include the widespread pain index (WPI) and the symptom severity scale (SSS). Participants were further questioned regarding stressful experiences during their work and about post-traumatic symptoms as well as regarding work performance and motivation. RESULTS: 321 participants were recruited (79.4% female, 20.6 male). 30 individuals (9.3%) of the sample fulfilled current criteria for a diagnosis of FM, with a rate of 11.4% among females and 1.5% among males. While specific symptoms such as fatigue and irritable bowel symptoms were negatively correlated with work performance, no significant difference was found between teachers with or without fibromyalgia regarding work attendance and performance. FM symptoms were strongly correlated with work-related stress and were strongly correlated with post-traumatic stress disorder (PTSD) related symptoms. Motivation to work was significantly lower among teachers fulfilling FM criteria, but other performance-related parameters did not differ between teachers fulfilling or not fulfilling FM criteria. CONCLUSIONS: Fibromyalgia symptoms are highly prevalent among Israeli school teachers, and may be related to stress encountered in the classroom. These results are relevant both for physicians treating individuals involved in educational careers as well as for educators and decision-makers involved in planning and managing educational strategies.

Brain responses to other people's pain in fibromyalgia: a magnetoencephalography study.

OBJECTIVES: We investigated whether the central pain symptoms in fibromyalgia syndrome (FM) are related to defective top-down sensorimotor regulation. The pain matrix was activated in a top-down manner by presenting pictures of painful situations while recording brain activity using magnetoencephalography (MEG). We investigated alpha desynchronisation in FM patients and healthy controls in response to pictures depicting pain. METHODS: 19 FM patients and 14 age-matched healthy controls (age 20-60) were recruited. Participants were shown photographs of right hands and feet in situations depicting pain or of control situations with no depiction of pain. MEG was recorded in a whole-head 248-sensor system as subjects laid supine. RESULTS: In healthy controls exposure to pictures depicting painful situations elicited a decrease in alpha activity (10Hz) at 100-500ms post-stimulus, which was significantly more pronounced than the one elicited by non-painful content mostly on sensors above the right sensorimotor cortex. However, FM patients did not show significant differences in alpha activity between responses to pain and no-pain pictures. CONCLUSIONS: Consistent with previous findings, healthy participants displayed stronger alpha desynchronisation for pain pictures, indicating automatic disinhibition of the sensorimotor cortices in response to the observation of pain in others. We found evidence for a deficient modulation of sensorimotor cortex in FM patients. The lack of differential response suggests that they perceived relatively neutral pictures as potentially painful, at least in this setting. Our findings suggest that defective top-down regulation may play a role in the pathogenesis of FM.

Does the cognitive index of the symptom severity scale evaluate cognition? Data from subjective and objective cognitive measures in fibromyalgia.

OBJECTIVES: The current provisional diagnostic criteria for the fibromyalgia syndrome (FM) include a cognitive index score (SSS-Cog), which constitutes a part of the Symptom Severity Scale (SSS). The current study aimed at assessing the validity of the cognitive index score, by comparing this subjective measure of cognitive impairment with an objective measure of cognitive functioning, collected through comprehensive computerised cognitive testing and assessment. METHODS: 50 FM patients underwent a computerised cognitive assessment battery, including testing in domains of memory, executive function, attention and information processing speed (NeuroTraxCorp.). Age and education standardised scores were computed. FM symptoms were assessed by the Fibromyalgia Impact Questionnaire (FIQ), Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), a Visual Analog Scale (VAS) of clinical pain and the Beck Depression inventory (BDI-II). RESULTS: The index score for subjective assessment of cognitive decline (SSS-Cog) was not correlated with any of the objective cognitive measures. However, a positive correlation was found between the SSS-Cog and the FIQ, the WPI and the VAS measures, all reflecting subjective overall functional ability. CONCLUSIONS: No significant relationship was found between FM patients' subjective appraisal of cognitive deficit and objective cognitive scores on all computerised subtests. However, subjective appraisal of cognitive impairment was found to be strongly and significantly related to patients' functional ability. Therefore, we suggest reconsidering the definition of this index score (SSS-Cog) and propose developing novel and more accurately defined tools in order to measure cognitive impairment in FM patients, for both diagnostic and epidemiological purposes.

Self-reported childhood maltreatment, lifelong traumatic events and mental disorders in American and Israeli rheumatoid arthritis patients.

OBJECTIVES: Psychological stress is thought to play a major role in the development and exacerbation of autoimmune diseases in general, as well as in rheumatoid arthritis (RA) in particular. The aims of the current study are to compare retrospective self-reports of childhood maltreatment and lifetime major life/traumatic experiences of American and Israeli RA patients, using standardised instruments, while adjusting for concomitant mental disorders and psychological distress, in order to rule out their part in the subjective reports, thus addressing the trans-cultural robustness of the association between childhood maltreatment, traumatic experiences and RA. METHODS: RA patients at the participating study centres were recruited by their physicians, both in Israel and the USA. Patients filled out questionnaires regarding demographic data, disease activity, psychological distress, potential anxiety and potential depression. In addition, patients answered questions regarding pain and childhood maltreatment. RESULTS: 83 RA patients were recruited in the US and 23 patients in Israel. The comparison of CTQ-subscales between the US and Israeli cohorts showed significant differences between the groups only in the subscales of emotional neglect (US 10.30±5.05, Israeli 22.67±3.68, p<0.05) and emotional abuse (US 10.46±5.77, Israeli 7.13±4.84, p<0.05). 87% of Israeli patients had severe emotional neglect. Severe emotional abuse was associated with probable depression (OR 7.778, CI [1.907-31.716]). Using Pain Disability Index (PDI) score, Americans reported more pain during sexual activity than Israelis (US PDI Score 5.64±3.70. Israeli 3.16±3.86, p<0.05). PDI score was also associated with a previous traumatic event (36.89±18.57 vs. 16.82±14.85, p<0.05). CONCLUSIONS: A high degree of similarity was demonstrated between American and Israeli populations of RA patients, regarding psychological stressors and previous traumatic events. As expected, the results indicated a link between emotional abuse and depression in these patients. In addition, a previous traumatic event was associated with more significant pain. Physicians caring for RA patients should be vigilant regarding the possible association with childhood adversity and should consider appropriate consultations when indicated. In addition, while dealing with pain management in RA patients, physicians should keep in mind the possible contribution of distant childhood adversity.

Increased Sympathetic Outflow Induces Adaptation to Acute Experimental Pain.

BACKGROUND: There are interrelationships between the autonomic nervous system and pain. This study aims to explore the effect of different autonomic manipulations on pain perception and modulation. METHODS: Twenty healthy subjects (10 men and 10 women, mean age 25 ± 3 years) participated in this single-blinded, semi-randomized, controlled study, which included 2 study visits. Warm detection thresholds, heat pain thresholds, conditioned pain modulation (CPM), and pain adaptation were tested before and after administration of phenylephrine, clonidine, yohimbine, and saline. RESULTS: Changes in heart rate and blood pressure were found after all the pharmacological interventions. The only effect on pain measures was that yohimbine enhanced pain adaptation capacity while phenylephrine reduced it (P = 0.032). Several significant correlations were found between autonomic and pain parameters; greater decreases in heart rate after phenylephrine were associated with reduced pain ratings (r2 = 0.288, P = 0.018). In addition, enhanced pain adaptation was associated with higher total vascular resistance (r2 = 0.442, P = 0.01). CONCLUSIONS: Different effects of acute autonomic manipulations on experimental pain were found: an increase in sympathetic tone induced by yohimbine led to reduced pain sensitivity; a decrease in sympathetic tone with no effect on vagal-parasympathetic tone induced by phenylephrine led to reduction in pain adaptation capacity; and a decrease in sympathetic tone and increase in vagal parasympathetic tone by clonidine led to no change in pain adaptation capacity. While increased sympathetic outflow does facilitate pain adaptation, activation of either the sympathetic or parasympathetic limbs of the autonomic nervous system does not affect pain thresholds or CPM. Finally, a correlation exists between nociception and cardiovascular parameters only due to baroreflex activation.