Sensitive skin syndrome (SSS) is commonly reported despite its nonspecific definition, whereas peripheral neuropathy (PN) remains underrecognized in the general population. Because localized paresthesia and numbness—particularly in the hands and feet—may be perceived as skin problems, some patients reporting sensitive skin could have unrecognized neuropathy. This exploratory real-world evidence study investigated the potential overlap between SSS and PN. Patient-level real-world data from health records of individuals reporting sensitive skin were analyzed to characterize associated diagnoses, symptoms, comorbidities, and risk factors potentially related to PN. Diagnoses among patients reporting sensitive skin included dermatitis (44%), altered skin sensation (33%), dry skin or urticaria (15%), and acne (13%). Within the group diagnosed with altered skin sensation, 18% reported paresthesia or tingling, 11% reported anesthesia or numbness, and 4% reported other symptoms. Documented comorbidities and risk factors included established contributors to PN, such as diabetes, cardiovascular disease, and smoking. The findings suggest a potential diagnostic overlap between SSS and PN and raise the hypothesis that some patients with altered skin sensation may have unrecognized PN. They also demonstrate how real-world data can reveal symptom patterns that may be overlooked during routine clinical assessment. Because the hypothesis arose from the same dataset used to explore it, these findings should be considered hypothesis-generating and require prospective confirmation. Nevertheless, timely differentiation between SSS and PN could facilitate appropriate clinical evaluation and improve patient health and well-being.
While total knee arthroplasty (TKA) generally provides excellent pain relief, a substantial minority of patients develop persistent postsurgical pain. This study investigated whether the early postoperative contraction rate of whole-body spatial pain extent was associated with moderate-to-severe knee pain 12 months after TKA. In this retrospective cohort study of patients undergoing primary unilateral TKA, participants completed whole-body pain drawings at 2 weeks, 6 weeks, and 3 months postoperatively. The Pain Extent Index (PEI) was calculated using a semiautomated image-processing workflow. The primary exposure was the patient-specific rate of PEI change between week 2 and month 3, determined via linear mixed-effects modeling. The primary outcome was moderate-to-severe operated-knee pain at 12 months. Logistic regression evaluated this association, adjusting for baseline covariates and static pain measures. At 12 months, 92 patients (14.7%) reported moderate-to-severe knee pain. Slower spatial pain contraction was significantly associated with higher odds of 12-month pain (adjusted odds ratio per 1-SD slower contraction, 1.42; 95% CI, 1.03–1.95). This association remained significant even after adjusting for baseline risk factors and static pain intensity and extent at both week 2 and month 3. Slower contraction was also correlated with poorer 12-month joint-related functional outcomes, including lower KOOS-JR scores (P < 0.001). Slower contraction of spatial pain extent during the subacute recovery phase was associated with moderate-to-severe knee pain and inferior functional outcomes 1 year after TKA.
Research examining relationships between pain and cognition in dementia and cognitive impairment has expanded, yet methodological and cultural limitations remain insufficiently explored. This paper critically synthesises findings from two scoping reviews focusing on pain-cognition relationships in dementia, methodological approaches used in assessing these constructs, and the influence of cultural factors on pain and cognition. Across the included reviews, evidence suggests chronic pain was generally associated with poorer cognitive performance, particularly in domains such as executive functioning and processing speed, although findings varied across studies. This variation may partly reflect differences in measurement tools and study design, particularly the use of global screening tools versus domain-specific cognitive assessments. The synthesis indicates that interpretation of evidence in this area is shaped by inconsistent cognitive assessment practices and reliance on pain measures that become less appropriate with cognitive decline. The review argues that culturally informed and multimodal approaches are required to improve assessment validity and advance dementia research and care.
Chronic musculoskeletal disease in Canis lupus familiaris (dogs) is associated not only with biomechanical dysfunction but also with alterations in autonomic regulation, affective processing, movement behavior, and chronic pain adaptation. Current rehabilitation models primarily emphasize peripheral tissue healing and biomechanics while placing less emphasis on interactions among interoception, nociception, autonomic regulation, and affective-motor processing. The objective of this Hypothesis and Theory article is to present the Cingulate–Mitochondrial–Resonome Axis (CMRA), a systems-level framework proposing that rehabilitation acts in part by restoring the coherence and organization of interoceptive signaling (the resonome), thereby influencing cingulate-mediated affective, autonomic, nociceptive, and motor regulation. Building conceptually upon the Feelings of Knowing–Fundamental Interoceptive Patterns (FoK–FIP) theory, the CMRA framework proposes that distributed interactions among connective tissue, autonomic, sensorimotor, and bioenergetic systems contribute to organism-level adaptation during rehabilitation. The central hypothesis is that restoration of interoceptive coherence serves as a candidate mediating variable linking peripheral rehabilitation interventions to central neurocognitive and behavioral change. Within this framework, functional improvements may occur despite persistent structural pathology, and rehabilitation-induced effects may extend beyond predictions made by strictly local biomechanical models. These predictions distinguish the CMRA framework from conventional structure-centered rehabilitation models and generate experimentally testable hypotheses for future investigation. The manuscript further proposes that rehabilitation-associated physiological changes may be reflected by multimodal measures including infrared thermography, quantitative gait analysis, and validated behavioral assessments. While these measures are not specific to CMRA and may also reflect established mechanisms such as altered biomechanics, reduced inflammation, central sensitization, and predictive processing, the framework predicts coordinated changes across multiple domains consistent with improved interoceptive organization. The CMRA framework is presented as a testable theoretical model rather than an established mechanistic explanation. Although the proposed role of large-scale endogenous electromagnetic organization remains speculative and incompletely validated, the framework generates falsifiable predictions regarding rehabilitation-associated changes in behavior, autonomic regulation, gait function, and chronic pain adaptation across species.
Andrei Cristinel Dragnea, Lars Michels, Till Fellner, Argyro Christou, Giovanna Brandi, Giulio Bicciatto, Riccardo Ludovichetti, Thomas Frauenfelder, Zsolt Kulcsar, Meritxell Garcia Alzamora
There is no general consensus on which music genre is most effective for a specific condition. The impact of music on subjective pain perception during intravenous cannulation for a magnetic resonance imaging (MRI) scan was investigated. 204 patients were assigned to one of four groups: listening to Mozart, favorite music, relaxation music, or no music (control). Pain was assessed using the Visual Analogue Scale at four time points. Favorite music significantly reduced pain perception both 30 s and 2 min after puncture while Mozart showed a trend towards reduced pain perception 2 min after puncture. When including only patients with baseline pain (n = 71), a significant pain reduction was also observed in the Mozart group 2 min, with borderline significance 30 s after puncture, whereas the favorite music group not only intensified reduced pain perception 30 s and 2 min but also caused significant pain reduction immediately after puncture. No effect on pain was found for the relaxation music and control groups. Music may be effective for pain relief in unpleasant settings involving short painful interventions. Favorite music should be considered first, whereby patients with baseline pain could also benefit from listening to Mozart, indicating a potential “Mozart effect” in this subgroup. These exploratory results need to be validated in future studies including a higher number of patients.
