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Chronic pain induces a multitude of harmful effects; recently it has been suggested that chronic pain is also associated with premature aging, manifested in shortened telomere length (TL). However, evidence for this hypothesis is scarce and inconsistent. The aim was twofold: 1) Investigate whether chronic pain is associated with premature aging, and 2) Determine whether physical exercise (PE) moderates this association if it exists. Participants were 116 male subjects, with (n=67) and without chronic pain (n=49). Blood samples for TL analysis were collected and participants were interviewed and completed questionnaires. As a part of the cohort, we included people with physical disability; this variable was controlled in the analysis. The TL of individuals with chronic pain was significantly shorter than that of pain-free individuals. Regression analysis revealed a significant moderating effect of PE on chronic pain and TL, above and beyond the effects of disability, age, and weight. Whereas chronic pain was associated with shorter telomeres in participants who did not exercise, this association was non-significant among participants who did exercise. The results suggest that chronic pain is associated with premature ageing; however, PE may mitigate this association and may protect individuals against the harmful effects of chronic pain. PERSPECTIVE: The study suggest that it is important to monitor signs of premature ageing among chronic pain patients as they are at risk. However, chronic pain patients may benefit from regular physical exercise in this respect as it may moderate premature ageing.
Learn More >The concentration of the multifunctional protein clusterin is reduced in the plasma of subjects with degenerative scoliosis and carpal tunnel syndrome but elevated in the cerebrospinal fluid of neuropathic pain patients successfully treated with spinal cord stimulation. The present work tries to increase the knowledge of pain-associated changes of plasma and brain clusterin by using an animal model of neuropathy. We studied the effects of sciatic nerve ligation on mechanical allodynia (von Frey test), anxiety (elevated plus maze test), plasma clusterin (enzyme-linked immunosorbent assay) and clusterin expression in the nucleus accumbens and prefrontal cortex of adult male Wistar rats (western blot). The possible modulatory role of high fat dieting was also studied, bearing in mind that obesity has been also reported to influence nociception, clusterin levels and prefrontal cortex activation. Animals with nerve ligation showed mechanical allodynia, anxiety and a marked downregulation of clusterin in the mitochondrial fraction of the prefrontal cortex. Animals fed on high fat also exhibited a slight increase of the sensitivity to mechanical stimuli and anxiety; however, the diet did not potentiate the effects of nerve ligation. The results did not confirm a parallelism between neuropathy, obesity and alterations of plasma levels of clusterin, but strongly suggest that the protein could be involved in the functional reorganization of the prefrontal cortex which has been recently reported in chronic pain conditions.
Learn More >Central sensitization represents a key pathophysiological mechanism underlying the development of neuropathic pain, often manifested clinically as mechanical allodynia and hyperalgesia. Adopting a mechanism-based treatment approach relies highly on the ability to assess the presence of central sensitization. The aim of the study was to investigate potential pain-autonomic readouts to operationalize experimentally induced central sensitization in the area of secondary hyperalgesia.
Learn More >We aimed to systematically assess the effectiveness and tolerability of erenumab in a clinical setting, specifically a tertiary headache center.
Learn More >In this study we aimed to evaluate the frequency of the main red flags in patients with headache who do have Covid-19.
Learn More >Chronic pain is one of the most common and interfering symptoms experienced by people with MS. There is an opportunity to shift the paradigm from interventions delivered after pain has become chronic to early, proactive interventions to alter the impact of MS-related pain. The purpose of this study was to develop and test a remotely delivered single-session group intervention to modify the pain trajectory for individuals with early MS. Research Method/Design: This was a single-center 2-group pilot randomized (1:1) controlled trial comparing a novel videoconference-delivered single-session pain intervention to a waitlist control. Participants were = 27 adults who were diagnosed with MS in the preceding 36 months and who had moderate or worse pain. The study team developed the intervention to introduce pain coping and commonly used cognitive, behavioral, and acceptance-based approaches for adaptive coping. Participants completed outcome assessments on pain intensity, interference, and coping at pretreatment, posttreatment, and 3-months posttreatment.
Learn More >Low back pain is prevalent in older populations and modifiable risk factors may include being overweight or obese. This study aimed to describe the prevalence and impact of moderate or severe low back pain in community-dwelling older adults and its association with body mass index (BMI).
Learn More >The prevalence of chronic widespread pain (CWP) in people with HIV is high, yet the underlying mechanisms are elusive. Leukocytes synthesize the endogenous opioid, β-endorphin, within their endoplasmic reticulum (ER). When released into plasma, β-endorphin dampens nociception by binding to opioid receptors on sensory neurons. We hypothesized that the heme-dependent redox signaling induces ER stress, which attenuates leukocyte β-endorphins levels/release, thereby increasing pain sensitivity in people with HIV. Results demonstrated that HIV positive individuals with CWP had increased plasma methemoglobin, erythrocytes membrane oxidation, hemolysis, and low plasma heme scavenging enzyme, hemopexin, compared to people with HIV without CWP and HIV-negative individuals with or without pain. In addition, the leukocytes from people with HIV with CWP had attenuated levels of the heme metabolizing enzyme, heme oxygenase-1, which metabolizes free heme to carbon-monoxide and biliverdin. These individuals also had elevated ER stress, and low β-endorphin in leukocytes. In vitro, heme exposure or heme oxygenase-1 deletion, decreased β-endorphins in murine monocytes/macrophages. Treating cells with a carbon-monoxide donor or an ER stress inhibitor, increased β-endorphins. To mimic hemolytic effects in a preclinical model, C57BL/6 mice were injected with phenylhydrazine hydrochloride (PHZ). PHZ increased cell-free heme and ER stress, decreased leukocyte β-endorphin levels and hindpaw mechanical sensitivity thresholds. Treatment of PHZ-injected mice with hemopexin blocked these effects, suggesting that heme-induced ER stress and a subsequent decrease in leukocyte β-endorphin is responsible for hypersensitivity in people with HIV.
Learn More >Neuroimmune-related sex differences contribute to the complexity of neurological disorders, such as drug abuse, depression, and chronic pain. The collection of articles presented in this issue add to our understanding of sex as a critical biological variable in the study of psychiatric and neurological diseases. Consideration of sex in the design and interpretation of study results is critical. Sex differences may warrant different treatment approaches for diseases in which sex or gender influences disease outcomes. The studies and reviews presented here examine the contribution of sexual dimorphism in the physiological responses and pharmacological treatments of neurological and psychiatric disorders.
Learn More >Effective treatment of neuropathic pain is challenging as its underlying mechanism remains largely unknown. Recently, the participation of brain-derived neurotrophic factor (BDNF) in neuropathic pain has been attracting increased attention. BDNF binds to a member of the tyrosine kinase receptor family, the TrkB receptor, that is specific for BDNF and is the transmembrane receptor on the posterior horn of spinal cord. In the present study, we purified two proteins that included the BDNF-binding domain of TrkB (eTrkB) and eTrkB coupled with a liposomal outer surface (liposomal eTrkB) in order to inhibit the BDNF-TrkB pathway in neuropathic pain. Results of the pull-down assay showed that eTrkB was bound to BDNF. We investigated the neuropathic pain suppression effect of this purified protein by its intrathecal administration in a rat neuropathic pain model. Mechanical and thermal hyperalgesia induced by L5 lumbar nerve ligation was markedly suppressed by treatment with eTrkB protein. Furthermore, we showed a prolonged algetic inhibition by liposomal eTrkB protein treatment. In conclusion, this study suggests that eTrkB, which sequesters endogenous BDNF and inhibits the BDNF-TrkB pathway, may prove to be a novel analgesic to treat neuropathic pain.
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