leptin and Chronic-Pain

Chronic pain is a devastating condition affecting the physical, psychological, and socioeconomic status of the patient. Inflammation and immunometabolism play roles in the pathophysiology of chronic pain disorders. Electrical neuromodulation approaches have shown a meaningful success in otherwise drug-resistant chronic pain conditions, including failed back surgery, neuropathic pain, and migraine. A literature review (PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles) was performed using the following search terms: chronic pain disorders, systemic inflammation, immunometabolism, prediction, biomarkers, metabolic disorders, and neuromodulation for chronic pain. Experimental studies indicate a relationship between the development and maintenance of chronic pain conditions and a deteriorated immunometabolic state mediated by circulating cytokines, chemokines, and cellular components. A few uncontrolled in-human studies found increased levels of pro-inflammatory cytokines known to drive metabolic disorders in chronic pain patients undergoing neurostimulation therapies. In this narrative review, we summarize the current knowledge and possible relationships of available neurostimulation therapies for chronic pain with mediators of central and peripheral neuroinflammation and immunometabolism on a molecular level. However, to address the needs for predictive factors and biomarkers, large-scale databank driven clinical trials are needed to determine the clinical value of molecular profiling.

Topics: Animals; Biomarkers; Chronic Pain; Humans; Inflammation Mediators; Leptin; Metabolic Networks and Pathways; Pain Management; Pain Measurement; Signal Transduction

The aim was to study associations between chronic widespread pain, widespread pain sensitivity, leptin, and metabolic factors in individuals with knee pain. A secondary aim was to study these associations in a subgroup of individuals with normal BMI.. This cross-sectional study included 265 individuals. The participants were categorised into three different pain groups: Chronic widespread pain (CWP), chronic regional pain (ChRP), or no chronic pain (NCP). The pressure pain thresholds (PPTs) were assessed using computerised pressure algometry. Low PPTs were defined as having PPTs in the lowest third of all tender points. Leptin and metabolic factors such as BMI, visceral fat area (VFA), lipids, and glucose were also assessed.. Sixteen per cent reported CWP, 15% had low PPTs, and 4% fulfilled both criteria. Those who fulfilled the criteria for CWP were more often women, more obese, and had increased leptin levels. In logistic regression, adjusted for age and gender, leptin was associated with fulfilling criteria for CWP, OR 1.015 (95% CI 1.004-1.027, p = 0.008). In logistic regression, adjusted for age and gender, leptin was associated with low PPTs, OR 1.016 (95% CI 1.004-1.029, p = 0.012). Leptin was also associated with fulfilling both criteria, adjusted for age, sex, and visceral fat area (VFA), OR 1.030 (95% CI 1.001-1.060), p = 0.040.. Leptin was associated with fulfilling the combined criteria for chronic widespread pain and low PPTs, even after adjusting for the visceral fat area (VFA). Longitudinal studies are needed to study the causal relationships between leptin and the development of widespread pain.. clinicalTrials.gov Identifier: NCT04928170.

Topics: Chronic Pain; Cross-Sectional Studies; Female; Humans; Leptin; Pain Measurement; Pain Threshold

Different functional somatic syndromes (FSS), fibromyalgia (FMS) and other unexplained painful conditions share many common clinical traits and are characterized by troubling and functionally disabling somatic symptoms. Chronic pain is most frequently reported and at the center of patients' level of disease burden. The construct of multisomatoform disorder (MSD) allows to subsume severely impaired patients suffering from FSS, FMS and other unexplained painful conditions to be examined for common underlying processes. Altered leptin levels and a pathological response of the HPA-axis as a result of chronic stress and childhood trauma have been suggested as one of the driving factors of disease development and severity. Previous studies have demonstrated that methylation of the leptin promoter can play a regulatory role in addiction. In this study, we hypothesized that methylation of the leptin promoter is influenced by the degree of childhood traumatization and differs between patients with MSD and controls. A cohort of 151 patients with MSD and 149 matched healthy volunteers were evaluated using clinical and psychometric assessment while methylation level analysis of the leptin promoter was performed using DNA isolated from whole blood.. In female controls, we found CpG C-167 to be negatively correlated with leptin levels, whereas in female patients CpG C-289, C-255, C-193, C-167 and methylation cluster (C-291 to C-167) at putative bindings sites for transcription factors Sp1 and c/EBPalpha were negatively correlated with leptin levels. Methylation levels were significantly lower in female patients CpG C-289 compared with controls. When looking at female patients with chronic widespread pain methylation levels were significantly lower at CpG C-289, C-255 and methylation cluster (C-291 to C-167).. Our findings support the hypothesis that epigenetic regulation of leptin plays a role in the regulation of leptin levels in patients with MSD. This effect is more pronounced in patients with chronic widespread pain.

Topics: Adult; Ambulatory Care Facilities; Chronic Pain; DNA Methylation; Female; Germany; Humans; Leptin; Middle Aged; Promoter Regions, Genetic; Somatoform Disorders

Low back pain (LBP) is a very frequent condition, affecting most people at some point throughout their life. This cross-sectional study was aimed to investigate a selected panel of cytokines and inflammatory biomarkers in patients with or without LBP.. The study population consisted of 104 patients diagnosed with LBP (52 non-persistent and 52 persistent) and 52 healthy subjects with no LBP. Blood samples were collected for assessment of adiponectin, leptin, monocyte chemoattractant protein-1 (MCP-1) and C reactive protein (CRP). The duration of LBP was categorized as "no pain", "non-persistent LBP" and "persistent LBP".. Higher values of CRP and lower concentrations of both leptin and MCP-1 were found in LBP patients compared to controls, whereas adiponectin did not differ among groups. MCP-1 was also lower in patients with non-persistent than in those with persistent LBP. Age, leptin (relative risk, 11.8; 95% CI, 3.9-35.8) and MCP-1 (relative risk, 2.7; 95% CI, 1.7-4.4) were independently associated with presence and duration of LBP. The combination of age, leptin and MCP-1 predicted 61% of the risk of LBP duration. The area under the curve of MCP-1 for distinguishing persistent from non-persistent LBP was 0.65 (95% CI, 0.54-0.76).. Then results of our study suggest that leptin and MCP-1 may be promising biomarkers for diagnosis of acute LBP and its risk to become chronic.

Topics: Aged; C-Reactive Protein; Chemokine CCL2; Chronic Pain; Female; Humans; Leptin; Low Back Pain; Male; Middle Aged; Prognosis; Time Factors

Obesity and chronic pain are often comorbid and their rates are increasing. It is unknown whether increased pain is caused by greater weight or poor diet quality or both. Therefore, we utilized a Total Western Diet (TWD) to investigate the functional and physiologic consequences of nutritionally poor diet in mice. For 13 weeks on the commercially available TWD, based on the National Health and Nutrition Examination Survey, thresholds of TWD-fed mice significantly increased in both thermal and mechanical tests. Quantitative magnetic resonance imaging revealed a significant increase in fat mass with a concomitant decrease in lean mass in the TWD-fed mice. In addition, there were significant increases in levels of serum leptin and inflammatory cytokines. After chronic pain induction using complete Freund's adjuvant, hypersensitivity was more pronounced and significantly prolonged in the TWD-fed mice. Therefore, prolonged exposure to poor diet quality resulted in altered acute nociceptive sensitivity, systemic inflammation, and persistent pain after inflammatory pain induction.. These results highlight the negative effects of poor diet quality with respect to recovery from hypersensitivity and susceptibility to chronic pain. A complete understanding of the impact of diet can aid in treatment and recovery dynamics in human clinical patients.

Topics: Animals; Chronic Pain; Cytokines; Diet, Western; Freund's Adjuvant; Hyperalgesia; Inflammation; Leptin; Male; Mice; Obesity; Pain Threshold

Endometriosis pain is a very common and extremely disabling condition whose mechanism is still poorly understood. While increased levels of leptin have been reported in patients with endometriosis, their contribution to endometriosis pain has not been explored. Using a rodent model of endometriosis we provide evidence for an estrogen-dependent contribution of leptin in endometriosis-induced pain. Rats implanted with autologous uterine tissue onto the gastrocnemius muscle developed endometriosis-like lesions and local chronic pain. Compared to eutopic uterine tissue, leptin mRNA and protein were up-regulated in the endometriosis-like lesions. Intramuscular injection of recombinant leptin in naive rats produced dose-dependent local mechanical hyperalgesia and nociceptor sensitization to mechanical stimulation. Ovariectomy attenuated the mechanical hyperalgesia induced by recombinant leptin, in rats treated with vehicle compared to those treated with 17β-estradiol replacement, at 1 and 24 h after leptin injection. Finally, intralesional injections of a pegylated leptin receptor (Ob-R) antagonist or of an inhibitor of Janus kinase2, which transduces the Ob-R signal, markedly attenuated pain in the endometriosis model. Taken together these data support the hypothesis that leptin, generated in ectopic endometrial lesions produces mechanical hyperalgesia by acting on nociceptors innervating the lesion. This sensitivity to leptin is dependent on estrogen levels. Thus, interventions targeting leptin signaling, especially in combination with interventions that lower estrogen levels, might be useful for the treatment of endometriosis pain.

Topics: Animals; Chronic Pain; Disease Models, Animal; Endometriosis; Endometrium; Enzyme Inhibitors; Estradiol; Estrogens; Female; Hyperalgesia; Janus Kinase 2; Leptin; Muscle, Skeletal; Nociceptors; Ovariectomy; Rats; Rats, Sprague-Dawley; Receptors, Leptin; RNA, Messenger; Touch; Uterus