Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain

Andersson, Maria; Thorén, Emelie; Sylwander, Charlotte; Bergman, Stefan

doi:10.1186/s12891-023-06773-4

Cited by 3 publications

(12 citation statements)

References 65 publications

(68 reference statements)

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“…We examined the bivariate correlations between the leptin/BMI ratio, ISI, HADS-A, HADS-D, and components of DAPSA for both sexes. As leptin exerts an effect on pain [21], we applied linear regression analysis for both the sexes, with the dependent variable being pain according to the visual analog scale (VAS), and the independent variables being the leptin/BMI ratio and the ISI, HADS-A, and HADS-D scores. Both the models were adjusted for treatment with tsDMARDs and bDMARDs.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the higher levels of leptin among women and its demonstrated link to pain in animal models [21,52], we found it interesting to include this determination in order to measure its sex-related influence on the disease activity parameters. We found that the leptin levels in women, adjusted for BMI, were associated with pain intensity.…”

Section: Discussionmentioning

confidence: 99%

“…Emotional factors were assessed using the Hospital Anxiety and Depression Scale (HADS), a 14-item scale applied to determine which individuals among those with medical conditions had anxiety and depression. Scores range from 0 to 21 for each subscale (HADS-D for depression and HADS-A for anxiety) and are classified as normal (0-7), borderline abnormal indicating a possible clinical disorder (8)(9)(10), and abnormal indicating a probable clinical disorder (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) [45].…”

Section: Leptin Emotional State and Sleep Qualitymentioning

confidence: 99%

“…Responses are on a 5-point Likert-type scale (0 to 4) for the previous month. The overall score ranges between 0 and 28 and is classified as no clinically significant insomnia (0-7), subthreshold insomnia (8)(9)(10)(11)(12)(13)(14), clinical insomnia (moderate severity) (15)(16)(17)(18)(19)(20)(21), and clinical insomnia (severe) (22)(23)(24)(25)(26)(27)(28) [46].…”

Section: Leptin Emotional State and Sleep Qualitymentioning

confidence: 99%

“…One of the first adipokines studied in this process is the leptin hormone, which is secreted mainly by adipose tissue, stimulated by ovarian sex hormones and inhibited by testosterone; therefore, the levels of this cytokine in the blood tend to be higher in women [17]. Leptin intervenes in the proinflammatory response by triggering the production of cytokines, such as TNF alpha and IL-6, stimulating differentiation between the Th1 and Th17 cells [18][19][20] and contributing to abnormal pain processing [21]. In terms of metabolic functions, leptin influences glucose metabolism by phosphorylating the insulin receptor and suppressing the glucose transporter which is involved in the development of insulin resistance [22].…”

Section: Introductionmentioning

confidence: 99%

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Clinical Features and Disease Activity in Psoriatic Arthritis: A Sex-Related Perspective on Leptin and Comorbidity

Toledano,

Gómez-Lechón,

Chacón

et al. 2024

JCM

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Background/Objectives: Many studies have addressed the sex differences in patients with psoriatic arthritis, although these are aimed more at describing the phenotype than at investigating the causes underlying these differences. The aims of our study were to assess the presence of clinical features in relation to sex, and to measure the effect on disease activity of different comorbidities in each sex. Methods: This was a cross-sectional study in which the following factors were measured: the clinical features of the disease, disease activity, the physical function and the disease impact. We measured serum leptin levels, to eliminate the effect of obesity on leptin levels, and a leptin/BMI ratio was calculated. The comorbid conditions evaluated included anxiety and depression, and sleep quality. Results: A total of 203 patients participated in this study. The mean age was 54.6 ± 11.3, and 46.8% of the patients were women. Women less frequently presented axial involvement (8% vs. 28%; p < 0.001) and more commonly had enthesitis (2 vs. 0.3; p < 0.001). They also had higher DAPSA (16.4 vs. 13.4; p < 0.001) and PsAID12 scores (4.1 vs. 2.9; p < 0.001), worse HAQ results (0.8 vs. 0.5; p < 0.001), and greater FACIT-F scores (32.7 vs. 38.1; p < 0.001). As for the comorbid conditions, women presented a higher leptin/BMI ratio (0.8 vs. 0.2; p < 0.001), higher levels of HADS-A (6.9 vs. 4.7; p < 0.001) and HADS-D (4.9 vs. 3.4; p < 0.001), and poorer ISI (9.3 vs. 7.0; p < 0.001). By sex, pain affecting women was associated with the leptin/BMI ratio (β: 0.29; p < 0.004; 95%CI: 0.3–1.6) and sleep quality (β: 0.31; p < 0.004; 95%CI: 0.04–0.25; R2: 0.26). The leptin/BMI ratio was not associated with pain in men (p = 0.46). Conclusions: Sex was associated with several clinical manifestations. Leptin/BMI ratio levels were associated with pain in women, but not in men.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Leptin Emotional State and Sleep Qualitymentioning

confidence: 99%

Section: Leptin Emotional State and Sleep Qualitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical Features and Disease Activity in Psoriatic Arthritis: A Sex-Related Perspective on Leptin and Comorbidity

Toledano,

Gómez-Lechón,

Chacón

et al. 2024

JCM

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IL-6 from cerebrospinal fluid causes widespread pain via STAT3-mediated astrocytosis in chronic constriction injury of the infraorbital nerve

Yu,

Cui,

Jin

et al. 2024

J Neuroinflammation

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Background The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread pain remain obscure. Methods A chronic constriction injury of the infraorbital nerve (CCI-ION) model was constructed, and pain-related behavior was observed on the 7th, 14th, 21st, and 28th days post surgery, in both vibrissa pads and hind paws. CSF from CCI-ION rats was transplanted to naïve rats through intracisternal injection, and thermal and mechanical allodynia were measured in hind paws. The alteration of inflammatory cytokines in CCI-ION’s CSF was detected using an antibody array and bioinformatic analysis. Pharmacological intervention targeting the changed cytokine in the CSF and downstream signaling was performed to evaluate its role in widespread pain. Results CCI-ION induced local pain in vibrissa pads together with widespread pain in hind paws. CCI-ION’s CSF transplantation, compared with sham CSF, contributed to vibrissa pad pain and hind paw pain in recipient rats. Among the measured cytokines, interleukin-6 (IL-6) and leptin were increased in CCI-ION’s CSF, while interleukin-13 (IL-13) was significantly reduced. Furthermore, the concentration of CSF IL-6 was correlated with nerve injury extent, which gated the occurrence of widespread pain. Both astrocytes and microglia were increased in remote segments of the CCI-ION model, while the inhibition of astrocytes in remote segments, but not microglia, significantly alleviated widespread pain. Mechanically, astroglial signal transducer and activator of transcription 3 (STAT3) in remote segments were activated by CSF IL-6, the inhibition of which significantly mitigated widespread pain in CCI-ION. Conclusion IL-6 was induced in the CSF of the CCI-ION model, triggering widespread pain via activating astrocyte STAT3 signal in remote segments. Therapies targeting IL-6/STAT3 signaling might serve as a promising strategy for the widespread pain symptom under neuropathological conditions. Graphical abstract

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Clinical Characteristics of Patients with Psoriatic Arthritis: Association between Sex and Comorbidity

Toledano,

Gómez-Lechón,

Chacón

et al. 2024

Preprint

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Many studies have addressed sex differences in patients with psoriatic arthritis, although these are aimed more at describing the phenotype than at investigating the causes underlying the differences. Cross-sectional study of 203 patients. The clinical and demographic variables included age, years of education, time since onset, smoking, type of treatment, clinical presentation, number of entheses affected, dactylitis, fatigue, and cutaneous involvement. Disease activity,functioning and disease was measured. The comorbid conditions evaluated included obesity (and leptin as an associated parameter), anxiety and depression, and sleep quality. Mean age was 54.6, and 46.8% of patients were women. Women less frequently presented axial involvement and more frequently presented enthesitis. They also presented greater disease activity, greater disease impact, and poorer functioning, as well as greater fatigue. As for comorbid conditions, women presented a higher leptin/BMI ratio, higher levels of anxiety and depression, and poorer sleep quality. By sex, pain affecting women was associated with the leptin/BMI ratio and sleep quality. The leptin/BMI ratio was not associated with any component of disease activity in men. Sex was associated with several clinical manifestations, disease activity, functioning, and disease impact. Leptin was associated with intensity of pain in women.

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Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain

Cited by 3 publications

References 65 publications

Clinical Features and Disease Activity in Psoriatic Arthritis: A Sex-Related Perspective on Leptin and Comorbidity

Clinical Features and Disease Activity in Psoriatic Arthritis: A Sex-Related Perspective on Leptin and Comorbidity

IL-6 from cerebrospinal fluid causes widespread pain via STAT3-mediated astrocytosis in chronic constriction injury of the infraorbital nerve

Clinical Characteristics of Patients with Psoriatic Arthritis: Association between Sex and Comorbidity

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