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Though chronic pain is widespread, affecting about one-fifth of the world's population, its impacts are disproportionately felt across the population according to socioeconomic determinants such as education and income. These factors also influence patients' access to treatment, including pharmacological pain management.
Learn More >Cachexia is a syndrome of unintentional body weight loss and muscle wasting occurring in 30% of all cancer patients. Patients with cancers most commonly leading to brain metastases have a risk for cachexia development between 20 and 80%. Cachexia causes severe weakness and fatigue and negatively impacts quality and length of life. The negative energy balance in cachectic patients is most often caused by a combination of increased energy expenditure and decreased energy intake. Basal metabolic rate may be elevated due to tumor secreted factors and a systemic inflammatory response leading to inefficiency in energy production pathways and increased energy demand by the tumor and host tissues. A growing body of research explores physiological and molecular mechanisms of metabolic dysregulation in cachexia. However, decreased energy intake and physical functioning also remain important contributors to cachexia pathogenesis. Pain associated with metastatic malignancy is significantly associated with inflammation, thus making inflammation a common link between cancer pain and cachexia. Pain may also influence appetite and food intake and exacerbate fatigue and functional decline, potentially contributing to cachexia severity. Cancer pain and cachexia often occur simultaneously; however, causal relationships remain to be established. Appropriate assessment and treatment of pain in advanced cancer patients may positively impact nutrition status and physical functioning, slowing the progression of cachexia and improving quality and length of life for patients.
Learn More >Recurrent or chronic pain affects 11-38% of children and adolescents. Pediatric pain research typically focuses on risk factors, such as anxiety and parent functional disability, but resilience-building, protective factors also play an important role in the pain experience. New methods to incorporate resilience-enhancing factors into pain research are needed. Photovoice is a highly participatory research method, where participants take photos to address a common question, caption their photos, and discuss the meaning of the photos in a group. The main objective of this study was to determine whether photovoice is an acceptable method to young people living with chronic pain for identifying and sharing sources of joy. Another objective was to explore sources of joy. Sixteen adolescents and young adults participated, which involved meeting in a group to discuss the goal of the study, taking photographs of self-identified sources of joy over a two-week period, and meeting as a group again to discuss the photographs and participate in a focus group about the experience. Results suggest that photovoice is an acceptable method, as all participants took photographs and attended both meetings, and three themes from the focus group data suggested the participants considered photovoice to be appropriate: 1.) Relief associated with meeting peers, 2.) Potential to benefit young people living with pain, and 3.) Potential to raise awareness. Three themes emerged from the discussion of the photographs to describe sources of joy: 1.) Gratitude for everyday pleasures and accomplishments, 2.) Support from pets, and 3.) Journey of acceptance. Results add to the strengths-based literature on pediatric pain by identifying an acceptable method that could be further explored for use as an intervention to enhance protective factors such as positive affect, gratitude, and social support and to compare the experiences of different populations of youth living with pain.
Learn More >Toll-like receptor 4 (TLR4) is a pattern-recognition receptor (PRR) that regulates the activation of immune cells, which is a target for treating inflammation. In this study, Cannabidivarin (CBDV), an active component of Cannabis, was identified as an antagonist of TLR4. , intrinsic protein fluorescence titrations revealed that CBDV directly bound to TLR4 co-receptor myeloid differentiation protein 2 (MD2). Cellular thermal shift assay (CETSA) showed that CBDV binding decreased MD2 stability, which is consistent with simulations that CBDV binding increased the flexibility of the internal loop of MD2. Moreover, CBDV was found to restrain LPS-induced activation of TLR4 signaling axes of NF-κB and MAPKs, therefore blocking LPS-induced pro-inflammatory factors NO, IL-1β, IL-6 and TNF-α. Hot plate test showed that CBDV potentiated morphine-induced antinociception. Furthermore, CBDV attenuated morphine analgesic tolerance as measured by the formalin test by specifically inhibiting chronic morphine-induced glial activation and pro-inflammatory factors expression in the nucleus accumbent. This study confirms that MD2 is a direct binding target of CBDV for the anti-neuroinflammatory effect and implies that CBDV has great translational potential in pain management.
Learn More >Tic disorders (TDs) are complex neurological conditions characterized by involuntary, persistent vocalizations and motor movements called tics. Tics involve brief muscle movements and can impair many aspects of daily functioning and quality of life in patients – and their physical nature can cause pain. Understanding individuals' experiences of tic-related pain and pain management could help explore this under-researched area and identify additional support needs for this population. The aim of this study was to investigate experiences of pain and use of pain management techniques in people with tic disorders.
Learn More >The multi-functional neuropeptide calcitonin gene-related peptide (CGRP) plays a major role in the pathophysiology of migraine. The detection of elevated CGRP levels during acute migraine headache was the first evidence of the importance of the peptide. Since then, elevated CGRP levels have been detected not only during spontaneous and experimentally induced migraine attacks but also interictally. However, the detection of CGRP in peripheral blood shows conflicting results. In this respect, alternative detection methods are needed and have been already proposed. This article summarizes what we have learned from studies investigating CGRP in jugular and peripheral blood and reviews the latest state of research concerning the detection of CGRP in saliva and tear fluid as well as their contribution to our understanding of migraine pathophysiology.
Learn More >Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients' quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.
Learn More >Chronic orofacial pain is prevalent and debilitating. Psychological and social factors place a heavy burden on this population but are often overlooked. Here, we offer the first comprehensive qualitative conceptualization of the challenges of living with chronic orofacial pain through a biopsychosocial perspective to inform multifaceted care for this population.
Learn More >Primary headache is a very common and disabling disease. The burden of pain and recurrent attacks may lead to a poor quality of life, anxiety and depression. An increased risk of low functioning and curricular performances in young patients with primary headache has been described. The mechanisms underlying the relationship between migraine and poor school achievement may be various and could be a reflection of weak cognitive skills. Data concerning the cognitive functioning in the free pain interval in pediatric age are under-investigated and results are far from conclusive. The present review article suggests that, though considered a benign disease, pediatric migraine may be associated to altered neuropsychological functioning in the interictal phase. Although children and adolescents with migraine generally have a normal intelligence, they may show a not homogeneous cognitive profile, characterized by possible difficulties in verbal skills, in particular comprehension abilities. Pediatric primary headache may present altered neuropsychological functioning involving attentional resources, processing speed and memory, particularly verbal memory. Given the impact that this disease can have on school performance and the tendency to persist from childhood to adulthood, a cognitive screening in young patients affected by primary headache is pivotal. Additional neuropsychological research using more homogenous methods is needed.
Learn More >Although activation of microglial cells is critical in developing brain disorders, their role in anxiety-like behaviors in pain is still vague. This study indicates that alteration of microglia's neuronal spine engulfment capacity in ventral zona incerta (ZI ) leads to significant pain and anxiety-like behaviors in mice 1-day post-injection of Complete Freud's Adjuvant (CFA1D). Performing whole-cell patch-clamp recordings in GABAergic neurons in the ZI (ZI ) in brain slices, we observed decreased activity in ZIv and reduced frequency of the miniature excitatory postsynaptic currents (mEPSCs) in ZI of CFA1D mice compared with the saline1D mice. Besides, chemogenetic activation of ZI significantly relieved pain and anxiety-like behaviors in CFA1D mice. Conversely, in naïve mice, chemogenetic inhibition of ZI induced pain and anxiety-like behaviors. Interestingly, we found changes in the density and morphology of ZI and increased microglial engulfment of spines in ZI of CFA1D mice. Furthermore, pain sensitization and anxiety-like behaviors were reversed when the ZI of CFA1D-treated mice were chemically inhibited by intra-ZI minocycline injection, accompanied by the recovery of decreased ZI excitability. Conclusively, our results provide novel insights that dysregulation of microglial engulfment capacity encodes maladaptation of ZI , thus promoting the development of anxiety-like behaviors in acute pain.
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