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Intervertebral disc degeneration (IVDD), for which obesity and genetics are known risk factors, is a chronic process that alters the structure and function of the intervertebral discs (IVD). Circulating leptin is positively correlated with body weight and is often measured to elucidate the pathogenesis of IVD degeneration. In this study, we examined the associations of single nucleotide polymorphisms (SNPs) genetic and environmental effects with IVDD. A total of 303 Taiwanese patients with IVDD (mean age, 58.6 ± 12.7 years) undergoing cervical discectomy for neck pain or lumbar discectomy for back pain were enrolled. Commercially available enzyme-linked immunosorbent assay (ELISA) kits measured the circulating plasma leptin levels. TaqMan SNP genotyping assays genotyped the SNPs rs2167270 and rs7799039. Leptin levels were significantly increased in obese individuals ( < 0.001) and non-obese or obese women ( < 0.001). In the dominant model, recoded minor alleles of rs2167270 and rs7799039 were associated with higher leptin levels in all individuals ( = 0.011, = 0.012). Further, the association between these SNPs and leptin levels was significant only in obese women ( = 0.025 and = 0.008, respectively). There was an interaction effect between sex and obesity, particularly among obese women (interaction = 0.04 and 0.02, respectively). Our findings demonstrate that these SNPs have sex-specific associations with BMI in IVDD patients, and that obesity and sex, particularly among obese women, may modify the transcription effect.

Degeneration of the intervertebral disc (IVD) is a major contributor to low back pain (LBP). IVD degeneration is characterized by abnormal production of inflammatory cytokines secreted by IVD cells. Although the underlying molecular mechanisms of LBP have not been elucidated, increasing evidence suggests that LBP is associated particularly with microglia in IVD tissues and the peridiscal space, aggravating the cascade of degenerative events. In this study, we implemented our microfluidic chemotaxis platform to investigate microglial inflammation in response to our reconstituted degenerative IVD models. The IVD models were constructed by stimulating human nucleus pulposus (NP) cells with interleukin-1β and producing interleukin-6 (129.93 folds), interleukin-8 (18.31 folds), C-C motif chemokine ligand-2 (CCL-2) (6.12 folds), and CCL-5 (5.68 folds). We measured microglial chemotaxis ( < 0.05) toward the conditioned media of the IVD models. In addition, we observed considerable activation of neurodegenerative and deactivation of protective microglia via upregulated expression of CD11b ( < 0.001) and down-regulation of CD206 protein ( < 0.001) by soluble factors from IVD models. This, in turn, enhances the inflammatory milieu in IVD tissues, causing matrix degradation and cellular damage. Our findings indicate that degenerative IVD may induce degenerative microglial proinflammation, leading to LBP development.

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological intervention used in the treatment of acute and chronic pain conditions. The first clinical studies on TENS were published over 50 years ago, when effective parameters of stimulation were unclear and clinical trial design was in its infancy. Over the last two decades, a better understanding of the mechanisms underlying TENS efficacy has led to the development of an adequate dose and has improved outcome measure utilization. The continued uncertainty about the clinical efficacy of TENS to alleviate pain, despite years of research, is related to the quality of the clinical trials included in systematic reviews. This summary of the evidence includes only trials with pain as the primary outcome. The outcomes will be rated as positive (+), negative (-), undecided (U), or equivalent to other effective interventions (=). In comparison with our 2014 review, there appears to be improvement in adverse events and parameter reporting. Importantly, stimulation intensity has been documented as critical to therapeutic success. Examinations of the outcomes beyond resting pain, analgesic tolerance, and identification of TENS responders remain less studied areas of research. This literature review supports the conclusion that TENS may have efficacy for a variety of acute and chronic pain conditions, although the magnitude of the effect remains uncertain due to the low quality of existing literature. In order to provide information to individuals with pain and to clinicians treating those with pain, we suggest that resources for research should target larger, high-quality clinical trials including an adequate TENS dose and adequate timing of the outcome and should monitor risks of bias. Systematic reviews and meta-analyses should focus only on areas with sufficiently strong clinical trials that will result in adequate sample size.

Negative pressure wound therapy (NPWT) has been described as an effective treatment for wounds of various etiologies, however it is expensive. Various authors have investigated low-cost alternatives to commercial NPWT devices. A systematic review summarizing their findings is needed for clinicians operating in resource-limited locations and for those interested in potential cost savings.

This study investigates thoracic hyper kyphosis (THK) rehabilitation using the Denneroll™ thoracic traction orthosis (DTTO). Eighty participants, with chronic non-specific neck pain (CNSNP) and THK were randomly assigned to the control or intervention group (IG). Both groups received the multimodal program; IG received the DTTO. Outcomes included formetric thoracic kyphotic angle ICT-ITL, neck pain and disability (NDI), head repositioning accuracy (HRA), smooth pursuit neck torsion test (SPNT) and overall stability index (OSI). Measures were assessed at baseline, after 30 treatment sessions over the course of 10 weeks, and 1-year after cessation of treatment. After 10 weeks, the IG improved more in neck pain intensity ( < 0.0001) and NDI ( < 0.001). No differences were found for SPNT ( = 0.48) and left-sided HRA ( = 0.3). IG improved greater for OSI ( = 0.047) and right sided HRA ( = 0.02). Only the IG improved in THK ( < 0.001). At 1-year follow-up, a regression back to baseline values for the control group was found for pain and disability such that all outcomes favored improvement in the IG receiving the DTTO; all outcomes ( < 0.001). The addition of the DTTO to a multimodal program positively affected CNSNP outcomes at both the short and 1-year follow-up.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin regulating synaptic plasticity, neuronal excitability, and nociception. It seems to be one of the key molecules in interactions between the central nervous system and immune-related diseases, i.e., diseases with an inflammatory background of unknown etiology, such as inflammatory bowel diseases or rheumatoid arthritis. Studies show that BDNF levels might change in the tissues and serum of patients during the course of these conditions, e.g., affecting cell survival and modulating pain severity and signaling pathways involving different neurotransmitters. Immune-related conditions often feature psychiatric comorbidities, such as sleep disorders (e.g., insomnia) and symptoms of depression/anxiety; BDNF may be related as well to them as it seems to exert an influence on sleep structure; studies also show that patients with psychiatric disorders have decreased BDNF levels, which increase after treatment. BDNF also has a vital role in nociception, particularly in chronic pain, hyperalgesia, and allodynia, participating in the formation of central hypersensitization. In this review, we summarize the current knowledge on BDNF's function in immune-related diseases, sleep, and pain. We also discuss how BDNF is affected by treatment and what consequences these changes might have beyond the nervous system.

Understanding of the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, as well as the formation of ectopic bone and osteophytes. Moreover, low-grade, chronic inflammation of the synovial lining has gained a central role in the definition of OA physiopathology, and central immunological mechanisms, innate but also adaptive, are now considered crucial in driving inflammation and tissue destruction. In addition, the role of neuroinflammation and central sensitization mechanisms as underlying causes of pain chronicity has been characterized. This has led to a renewed definition of OA, which is now intended as a complex multifactorial joint pathology caused by inflammatory and metabolic factors underlying joint damage. Since this evidence can directly affect the definition of the correct therapeutic approach to OA, an improved understanding of these pathophysiological mechanisms is fundamental. To this aim, this review provides an overview of the most updated evidence on OA pathogenesis; it presents the most recent insights on the pathophysiology of OA, describing the interplay between immunological and biochemical mechanisms proposed to drive inflammation and tissue destruction, as well as central sensitization mechanisms. Moreover, although the therapeutic implications consequent to the renewed definition of OA are beyond this review scope, some suggestions for intervention have been addressed.

Antioxidants and anti-inflammatory compounds are potential candidates to prevent age-related chronic diseases. Broccoli sprouts (BrSp) are a rich source of sulforaphane-a bioactive metabolite known for its antioxidant and anti-inflammatory properties. We tested the effect of chronic BrSp feeding on age-related decline in cardiometabolic health and lifespan in rats. Male and female Long-Evans rats were fed a control diet with or without dried BrSp (300 mg/kg body weight, 3 times per week) from 4 months of age until death. Body weight, body composition, blood pressure, heart function, and glucose and insulin tolerance were measured at 10, 16, 20, and 22 months of age. Behavioral traits were also examined at 18 months of age. BrSp feeding prolonged life span in females, whereas in males the positive effects on longevity were more pronounced in a subgroup of males (last 25% of survivors). Despite having modest effects on behavior, BrSp profoundly affected cardiometabolic parameters in a sex-dependent manner. BrSp-fed females had a lower body weight and visceral adiposity while BrSp-fed males exhibited improved glucose tolerance and reduced blood pressure when compared to their control counterparts. These findings highlight the sex-dependent benefits of BrSp on improving longevity and delaying cardiometabolic decline associated with aging in rats.

Workplace violence (WV) is a significant occupational hazard for nurses. Previous studies have shown that WV has a reciprocal relationship with occupational stress. Headaches and sleep problems are early neuropsychological signs of distress. This cross-sectional study aims to ascertain the frequency of physical or verbal assaults on nurses and to study the association of WV with headaches and sleep problems. During their regular medical examination in the workplace, 550 nurses and nursing assistants (105 males, 19.1%; mean age 48.02 ± 9.98 years) were asked to fill in a standardized questionnaire containing the Violent Incident Form (VIF) concerning the episodes of violence experienced, the Headache Impact Test (HIT-6) regarding headaches, and the Pittsburgh Sleep Quality Inventory (PSQI) on sleep quality. Occupational stress was measured using the Effort/Reward Imbalance questionnaire (ERI). Physical and non-physical violence experienced in the previous year was reported by 7.5% and 17.5% of workers, respectively. In the univariate logistic regression models, the workers who experienced violence had an increased risk of headaches and sleep problems. After adjusting for sex, age, job type, and ERI, the relationship between physical violence and headaches remained significant (adjusted odds ratio aOR = 2.25; confidence interval CI95% = 1.11; 4.57). All forms of WV were significantly associated with poor sleep in a multivariate logistic regression model adjusted for sex, age, job type, and ERI (aOR = 2.35 CI95% = 1.44; 3.85). WV was also associated with the impact of headaches and with sleep quality. WV prevention may reduce the frequency of lasting psychoneurological symptoms, such as headaches and poor sleep quality, that interfere with the ability to work.

Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release (27 patients, OXN patients) or Oxycodone Controlled Release (26 patients, OXY patients). The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction.