Background: Fibromyalgia (FM) is a chronic pain syndrome in which central sensitization has been suggested. Several patients also present with small fibre pathology. Neurofilament light chain (NfL) is a biomarker of axonal injury, but its role in FM remains unclear. We evaluated serum NfL in FM patients and tested possible correlations between NfL levels, clinical features, dysfunction at the central level assessed with a cognitive battery, and small fibre pathology assessed with skin biopsy.
Methods: We conducted an observational case-control study including 70 FM patients and 55 healthy controls. Serum NfL was measured using the LUMIPULSE G600II platform. Clinical assessment included pain (WPI), disability (FIQ), sleep (MOS Sleep Scale), and neuropsychological testing (MoCA and an executive function battery). Forty patients underwent skin biopsy with intraepidermal nerve fibre density (IENFD) quantification. Group comparisons were performed with non-parametric tests and correlations using Spearman coefficients.
Results: FM patients showed higher NfL levels compared to controls, independent of age. In both groups, NfL correlated positively with age (ρ = 0.25, p = 0.005). Among FM patients, NfL values did not differ between those with normal skin biopsy and those with proximal or combined proximal-distal denervation, and NfL did not correlate with IENFD. NfL was unrelated to disease duration, pain scores, sleep duration, or cognitive performance. The only clinical correlation observed was an association with disability (FIQ; ρ = 0.29, p = 0.02).
Conclusions: Serum NfL is elevated in FM but not linked to small fibre pathology or cognitive impairment. Instead, it may reflect neuronal changes related to disease burden.
Significance: These findings support the concept of FM as a neurogenic disorder and suggest serum NfL as a potential biomarker of neuronal stress in chronic pain, although it is not specific for peripheral nerve damage or cognitive dysfunction.
Background: A growing body of research reports positive consequences of acute pain, including emotional self-regulation. Pain as a pleasurable experience has also been regarded in the context of sadomasochistic (SM) interest, albeit quantitative empirical evidence is scarce. Recently, an elevated prevalence of chronic pain (CP) has been reported in SM practitioners; however, in absence of a control group. To contribute to research in the field, we strove to see whether we could replicate the finding and further aimed to identify psychological predictors of SM.
Method: A total of 617 participants (N = 242 with SM sexual preference) completed an online questionnaire battery comprising psychometric instruments for the measurement of pain attitudes, sensation seeking and pain sensitivity. An age- and sex-matched sample was created to control for their respective influence.
Results: CP prevalence in the SM subsample was 47.2%, which we found to be significantly increased compared to the prevalence in the non-SM subsample (29.4%). Neither sex nor age seemed to explain the relationship. There were no interaction effects of SM × CP on pain attitudes. A hierarchical logistic regression model explained around 42% of the variance in SM, with CP, sensation seeking, and viewing pain as a challenge as significant predictors.
Conclusions: We replicated an increased CP prevalence in SM and ruled out previous sampling biases. We further extended evidence on factors predicting SM sexual preference. Large-scale, representative and prospective studies are needed to corroborate the idea of SM as a coping strategy used by some CP patients.
Significance statement: We demonstrated a significantly elevated chronic pain prevalence of around 47% in individuals with sadomasochistic sexual preference, ruling out previously discussed sampling biases. Possibly, sadomasochistic practise is used as a coping strategy by some chronic pain patients. We further presented a model of pain-related and psychological variables explaining around 42% of variance in sadomasochistic sexual preference in general. The results are discussed in terms of their potential to inform pain management strategies.
Background: Shoulder-hand syndrome (SHS) is a neurological disorder characterised by pain, loss of function, and trophic changes in the shoulder and hand of the affected limb. SHS shares a number of features with Complex Regional Pain Syndrome (CRPS). Historically, several terms have been used interchangeably with SHS, obfuscating clinical presentation. This review aimed to characterise the presentation of SHS to provide a full clinical picture for clinicians and researchers. Furthermore, we aimed to examine whether symptoms differ between triggered and idiopathic SHS, as indicated in previous research.
Methods: A systematic search of three databases (PubMed, Web of Science and Google Scholar) and bibliographies was performed. Articles published from 1940 to 2025 describing symptoms of shoulder-hand syndrome in any context were screened for eligibility. Papers were excluded if they used alternative terms in place of 'shoulder-hand syndrome', such as reflex sympathetic dystrophy.
Results: 16,843 articles were identified, with 33 meeting the inclusion criteria. The clinical presentation of SHS was similar across included studies, with some variations observed between post-hemiplegic (PH) and post-myocardial infarction (PM) SHS patients. The predominant symptoms were pain in the shoulder, accompanied by pain and swelling of the hand. PH patients exhibited more trophic symptoms (e.g., nail growth changes, skin thickening), while PM patients demonstrated joint contractures and stiffness.
Conclusions: This review provides a detailed description of the symptoms of shoulder-hand syndrome, including both triggered and idiopathic cases. We hypothesize that SHS might be a sub-type of CRPS; however, more research is required to validate this categorization.
Significance statement: This review provides a detailed description of the symptoms of shoulder-hand syndrome. This information may be useful for clinicians and researchers examining cases of SHS and possibly contrast this with CRPS. A concerted effort to phenotype these patients, including the influence of inciting events, using modern techniques such as quantitative sensory testing would be useful. We propose that SHS may be a sub-type of CRPS and if confirmed should be classified accordingly, however more research is needed.
Objective: High blood pressure (BP) often co-occurs with osteoarthritis (OA) and may influence pain sensitivity, potentially contributing to pain-pathology discordance. We hypothesized that higher BP would associate with reduced pain sensitivity and greater OA severity in adults with chronic knee pain.
Methods: A cross-sectional analysis of 213 community-dwelling adults (44-78 years) with chronic knee pain was conducted. Hypertension was defined by diagnosis or antihypertensive use; others were normotensive. Systolic, diastolic, pulse (PP), and mean arterial (MAP) BP were measured. Quantitative sensory testing assessed pressure/thermal pain sensitivity, temporal summation (TS), and conditioned pain modulation (CPM). Radiographic knee OA (rKOA) was graded using the Kellgren-Lawrence scale. Models adjusted for race, age, BMI, site, and diabetes.
Results: Blood pressure-pain associations were moderated by sex and hypertensive status, observed only in normotensive individuals. Among normotensive males, each 10 mmHg increase in BP was associated with reduced pressure pain sensitivity (β [95% CI]: systolic -0.21 [-0.42, -0.002]; diastolic -0.36 [-0.68, -0.05]; MAP -0.31 [-0.59, -0.03]; all p < 0.05) but greater odds of late-stage rKOA (AOR [95% CI]: systolic 1.70 [1.07, 2.70]; MAP 2.10 [1.10, 4.01]). Among normotensive females, temporal summation of mechanical pain increased with higher BP (β [95% CI]: systolic 0.14 [0.01, 0.27], p = 0.027; PP 0.20 [0.02, 0.38], p = 0.026). No significant associations were observed for heat/cold pain sensitivity, TS of heat pain, or CPM.
Discussion: Elevated BP was associated with hypoalgesia and more severe rKOA severity in normotensive males. In normotensive females, elevated BP showed greater pain facilitation but not rKOA severity. Together, these sex-specific findings suggest BP as a vascular factor contributing to pain-pathology mismatch in OA.
Significance statement: Associations between arterial blood pressure and pain in older adults with knee pain were found to be sex- and hypertension-dependent, primarily evident in normotensive individuals. Elevated blood pressure was associated with reduced mechanical pain sensitivity but greater radiographic OA in normotensive males; normotensive females showed enhanced pain facilitation without increased OA severity. These findings support arterial pressure as a shared vascular factor in pain-pathology mismatch and highlight the importance of incorporating cardiovascular markers into chronic pain phenotyping and interpretation.
The Graded Chronic Pain Scale-Revised (GCPS-R) enables a standardised measure of chronic pain severity. Only sparse data are available on the prevalence of chronic pain stages assessed by the GCPS-R and the predictors of high-impact chronic pain (HICP) in the general European population.
A cross-sectional cohort study surveyed 2498 people ≥ 16 years living in Germany in 2025. Self-reported measures were obtained for demographic variables, chronic pain stages and disease load (Patient Health Questionnaire 4 and chronic illness). Potential predictors of HICP (age, gender, education, net income, probable depressive and anxiety disorder, chronic illness) compared to no and mild-impact and to bothersome chronic pain were assessed by adjusted univariate and multivariate logistic regression analyses.
Response rate was 37.9%. The prevalence of chronic pain present most or every day prior to 3 months was 11.4 (95% CI, 7.7% to 15.1%) of which 1.1% (−2.9% to 5.0%) with mild impact chronic pain; 3.3% (−0.6% to 7.2%) with bothersome impact chronic pain; and 7.1% (3.3% to 10.9%) with HICP. HICP compared to no and mild chronic pain was predicted in multivariate-adjusted analysis by age, lower educational level, lower income, probable anxiety and/or depressive disorder and chronic illness. Multivariate-adjusted analysis did not show significant associations of HICP with the selected variables when compared to bothersome pain.
Biological, psychological and social factors are associated with HICP. Targeted pain services for populations at highest risk for HICP need to be developed.
The prevalence of bothersome and high-impact chronic pain rather than prevalence rates of any chronic pain might provide evidence in support of pain specialist care. Identifying risk factors of high-impact chronic pain in specific populations could lead to an improved understanding of the risk factors, causes and consequences of chronic pain. European public health policies could be influenced by gathering data on high-impact chronic pain in other European countries.
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