The evaluation of chronic pain is challenging because of the lack of specific biomarkers. We identified the Mu opioid receptor-positive (Mu+) B cell percentage of expression, named Mu-Lympho-Marker (MLM), as a candidate marker for chronic pain in fibromyalgia (FM) and osteoarthritis (OA) patients. Here, we investigate the role of MLM on natural killer (NK) cells in the same patients. Twenty-nine FM and twelve OA patients were analyzed, and twenty-three pain-free subjects were considered as the control group. Blood samples were collected to perform immunophenotyping and Western blot analysis. Biological and clinical data were statistically analyzed. The final results showed that the percentage of NK cells expressing Mu was statistically lower in FM and OA patients than in pain-free subjects, as already demonstrated for B cells. A Western blot analysis was performed in order to detect NK cells’ functional status. Moreover, the correlation analysis of MLM expression with pharmacological therapy did not show any significant results. In conclusion, here, we confirm the role of MLM as a suitable marker for chronic pain and underline NK cells as a new possible immune cell type involved in the “Mu opioid receptor reserve theory”.

Full Papers; Authors: M. Tenti, W. Raffaeli, V. Malafoglia, M. Paroli, S. Ilari, C. Muscoli, E. Fraccaroli, S. Bongiovanni, C. Gioia, C. Iannuccelli, M. Di Franco, P. Gremigni

Fibromyalgia symptoms affect the sufferers’ working life; however, through reasonable accommodations in workplaces, they can continue to work satisfactorily. There are no Italian studies on factors that facilitate or hinder fibromyalgia-affected people’s working life. Our objective was to explore, in a pre-pandemic setting, the quality of working life of fibromyalgia sufferers and reasonable accommodations to improve it. Quantitative and qualitative methods were applied; a survey-questionnaire, participatory-developed, was online-administered to a sample of self-reported FM sufferers (N = 1176). Then, two Focus Groups (FGs), involving 15 fibromyalgia-affected women, were held. Data were analyzed by a thematic analysis approach. Among survey-respondents, 20% were unemployed and only 14% went to work gladly. Variability of pain (84%) and fatigue (90%) were the most perceived reasons for difficulties at work. Negative relationships at work were reported by most participants. The FGs’ discussions addressed different strategies for overcoming the main obstacle of “not being believed by colleagues and employers” and reasonable accommodations. However, a negative hopeless attitude towards the solution of problems at work was also apparent. Different critical issues in the workplace emerged from the survey and the FGs. Coordinated actions, according to a transdisciplinary approach, are needed to manage fibromyalgia-induced difficulties in the workplace.

Background/Objectives: Fibromyalgia (FM) is a chronic pain syndrome frequently associated with severe pain, sleep disturbances, worry, and depressive rumination. Although previous studies have shown links among these factors, no study has specifically examined the mediating role of sleep disturbances in the relationship between forms of Repetitive Negative Thinking (i.e., worry and rumination) and pain intensity. This study aimed to investigate whether sleep disturbances mediate the relationship between: (1) worry and pain intensity and (2) depressive rumination and pain intensity. Methods: An online cross-sectional survey was conducted with a sample of 867 Italian adults who reported having received an FM diagnosis from a rheumatologist or pain physician. After screening, 733 participants (97.3% female; mean age = 51.0 ± 9.95 years) were included in the analyses. Participants completed the Penn State Worry Questionnaire, the Ruminative Response Scale, the Brief Pain Inventory, and the Pittsburgh Sleep Quality Index. Mediation analyses were performed using Hayes’ PROCESS macro (Model 4). Results: Depressive rumination was associated with pain intensity both directly (B = 0.021, 95% Confidence Intervals [CIs] 0.012, 0.030) and indirectly through sleep disturbances (B = 0.014, 95% CIs 0.010, 0.020), indicating partial mediation. In contrast, worry showed no direct effect on pain intensity (B = 0.011, 95% CIs −0.003, 0.025) but demonstrated a significant indirect effect via sleep disturbances (B = 0.018, 95% CIs 0.012, 0.025), consistent with full mediation. Conclusions: Pain intensity, sleep quality, worry, and depressive rumination are interrelated in FM. Depressive rumination plays a particularly strong role in pain perception, independent of sleep quality. Interventions that integrate cognitive–behavioral and metacognitive strategies with sleep-focused treatments may help improve both sleep and pain outcomes in individuals with FM.

Fibromyalgia is a burdensome pain causing patients a very negative emotional state that can worsen their clinical profile, perceived disability, and treatment outcomes. In particular, anger can negatively affect pain and patient adjustment to the disease. Recent studies suggest that metacognitions and anger rumination can negatively affect anger, which in turn can amplify the intensity of pain. This study aims to investigate whether anger rumination and state anger serially mediate the relationship between metacognitions and the intensity of pain. The study included 446 subjects who: declared having received a fibromyalgia diagnosis by a rheumatologist/pain physician; completed measures of metacognitions, anger rumination, state-anger, and pain intensity. The serial mediation analysis was conducted using Hayes' PROCESS macro (Model 6). Negative beliefs about worry and beliefs about the need to control thoughts indirectly influenced the intensity of pain through two significant mediating pathways: state-anger and anger rumination to state-anger. Cognitive self-consciousness affected pain intensity directly (β = .11, p < .05) and indirectly through two significant mediating pathways: state-anger and anger rumination to state-anger. This study highlights the role of serial mediation of anger rumination and state-anger in the relationship between metacognitions and pain intensity in the field of fibromyalgia. Our work introduces new targets for anger management interventions for patients with fibromyalgia. Such interventions could be effectively addressed with a metacognitive approach considering its specific focus on dysfunctional metacognitive beliefs and repetitive negative thinking.

Background: Chronic pain (CP) prevalence estimates addressing a wide phenotype are still quite fragmented and may vary widely due to the lack of standardized tools of investigation. There is an urgent need to update general population CP estimates. Methods: For this purpose, the Brief Five-item Chronic Pain Questionnaire was developed through experts’ consultations for design and content validity assessment; literature analysis of measures used to investigate CP for general population surveys; understandability evaluation through a survey on a convenience sample of affected and non-affected individuals; reliability assessment by means of two double-wave online surveys carried out by the Italian Twin Registry; criterion and construct validity assessment through the third wave of the 2019 European Health Interview Survey (Ehis). Results: Key dimensions were defined to describe CP main aspects from a public health perspective. Literature analysis showed that validated questionnaires were rarely used to address important public health CP aspects. Understandability of the measure was good. Test-retest analyses showed adequate reliability of the measure: k values were at least “moderate” with highest values regarding CP “occurrence” and “intensity”. Correlations of CP with well-known comorbidities (cancer, depression), and specific traits (age, education) as well as of CP and its intensity with “physical pain occurrence and intensity” detected in the Ehis 2019, confirmed, respectively, a good construct and criterion validity. Construct validity was also evaluated through the correlation between “perceived treatment effectiveness” and “interference of pain in daily life activities” as recorded in the Ehis 2019. Conclusion: The designed questionnaire is a brief self-administered measure, particularly suitable to detect persistent states of pain and related intensity in large-scale general population surveys by means of a first filtering item followed by four further items. It is, in fact, designed to detect CP possible underlying causes/triggers, drugs/treatments taking and frequency, and self-perceived effectiveness among CP sufferers. Further validation of the measure in different social and cultural contexts is desirable.