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Chronic low back pain (CLBP) has been proved to be the dominating cause of disability in patients with lumbar degenerative diseases. Of the various etiological factors, intervertebral disc degeneration (IVDD) has been the dominating cause. In the past few decades, the role and changes of nerve systems, especially the peripheral sensory fibers and their neurotransmitters, in the induction and progression of IVDD have attracted growing concerns. The expression of many neuropeptides, such as SP, NPY, and CGRP, in the nociceptive pathways is increased during the progression of IVDD and responsible for the discogenic pain. Here, the role of CGRP in the progression of IVDD was firstly investigated both in vitro and in vivo. Firstly, we confirmed that human degenerated intervertebral disc tissue exhibited elevated expression of CGRP and its receptor. Secondly, in vitro experiments suggested that CGRP could inhibit the proliferation and induce apoptosis in human nucleus pulposus (NP) cells, as well as promote inflammation and degenerated phenotypes through activating NF-B and MAPK signaling pathways. Thirdly, CGRP receptor antagonist, Rimegepant, can ameliorate the adverse effects of CGRP imposed on NP cells, which were confirmed in vitro and in vivo. Our results will bring about a brand-new insight into the roles of neuromodulation in IVDD and related therapeutic attempts.
Learn More >Opioids are a class of drugs that are known for their use as pain relievers. They bind to opioid receptors on nerve cells in the brain and the nervous system to mitigate pain. Addiction is one of the chronic and primary adverse events of prolonged usage of opioids. They may also cause psychological disorders, muscle pain, depression, anxiety attacks etc. In this study, we present a collection of predictive models to identify patients at risk of opioid abuse and mortality by using their prescription histories. Also, we discover particularly threatening drug-drug interactions in the context of opioid usage. Using a publicly available dataset from MIMIC-III, two models were trained, Logistic Regression with L2 regularization (baseline) and Extreme Gradient Boosting (enhanced model), to classify the patients of interest into two categories based on their susceptibility to opioid abuse. We've also used K-Means clustering, an unsupervised algorithm, to explore drug-drug interactions that might be of concern. The baseline model for classifying patients susceptible to opioid abuse has an F1 score of 76.64% (accuracy 77.16%) while the enhanced model has an F1 score of 94.45% (accuracy 94.35%). These models can be used as a preliminary step towards inferring the causal effect of opioid usage and can help monitor the prescription practices to minimize the opioid abuse. Results suggest that the enhanced model provides a promising approach in preemptive identification of patients at risk for opioid abuse. By discovering and correlating the patterns contributing to opioid overdose or abuse among a variety of patients, machine learning models can be used as an efficient tool to help uncover the existing gaps and/or fraudulent practices in prescription writing. To quote an example of one such incidental finding, our study discovered that insulin might possibly be interacting with opioids in an unfavourable way leading to complications in diabetic patients. This indicates that diabetic patients under long term opioid usage might need to take increased amounts of insulin to make it more effective. This observation backs up prior research studies done on a similar aspect. To increase the translational value of our work, the predictive models and the associated software code are made available under the MIT License.
Learn More >Growing evidence suggests disparities in the prevalence, management, progression, and outcomes of chronic, nonmalignant pain-related conditions, especially for African American patients. The purpose of this review is to explore studied causative factors that influence the management of chronic pain among African Americans, including factors that result in disparate care that may contribute to unfavorable outcomes. This narrative review is based on available literature published on this topic published within the last 10 years. Assessment of chronic pain is multifaceted, often complicated by patient medical comorbidities and a complex set of biopsychosocial/spiritual/financial and legal determinants. These complexities are further exacerbated by a patient's race, by provider bias, and by structural barriers-all intersecting and culminating in disparate outcomes. A comprehensive analysis is needed to identify quality improvement interventions and to mitigate major barriers contributing to disparities in the management of chronic pain in the African American population.
Learn More >Migraine is a multifactorial neurological disorder with a major metabolic facet. Dietary approaches represent a commonly implemented lifestyle modifying strategy in headache clinics, yet the precise relationship between diet and migraine is still a matter of debate. The study consisted of two parts: first, in a cross-sectional design, we compared alimentary habits of migraine subjects and a control group of healthy volunteers. For the second part, we prospectively evaluated patients' daily consumption of various potentially migraine-triggering foods over a two-month period in order to examine their possible association with the occurrence of a migraine attack. Most migraine patients reported avoiding at least one potentially migraine-triggering food/drink from their diet. In spite of that, with the sole exemption of citrus fruits, there were no statistically significant differences with respect to consumption patterns between migraine patients and controls (including wine and chocolate). Consumption frequency over time was proportional to intake of potentially migraine-triggering foods the day before a migraine attack. Our results underline the need of performing trigger challenges in order to avoid falling into an association-causation fallacy when attempting to identify possible alimentary migraine triggers. Indeed, it is possible that intake of certain foods like chocolate before attacks is a consequence of pre-attack cravings or a simple coincidence facilitated by previously established dietary habits.
Learn More >Atopic dermatitis (AD) is a multifaceted, chronic relapsing inflammatory skin disease that affects people of all ages. It is characterized by chronic eczema, constant pruritus, and severe discomfort. AD often progresses from mild annoyance to intractable pruritic inflammatory lesions associated with exacerbated skin sensitivity. The T helper-2 (Th2) response is mainly linked to the acute and subacute phase, whereas Th1 response has been associated in addition with the chronic phase. IL-17, IL-22, TSLP, and IL-31 also play a role in AD. Transient receptor potential (TRP) cation channels play a significant role in neuroinflammation, itch and pain, indicating neuroimmune circuits in AD. However, the Th2-driven cutaneous sensitization of TRP channels is underappreciated. Emerging findings suggest that critical Th2-related cytokines cause potentiation of TRP channels, thereby exaggerating inflammation and itch sensation. Evidence involves the following: (i) IL-13 enhances TRPV1 and TRPA1 transcription levels; (ii) IL-31 sensitizes TRPV1 transcriptional and channel modulation, and indirectly modulates TRPV3 in keratinocytes; (iii) The Th2-cytokine TSLP increases TRPA1 synthesis in sensory neurons. These changes could be further enhanced by other Th2 cytokines, including IL-4, IL-25, and IL-33, which are inducers for IL-13, IL-31, or TSLP in skin. Taken together, this review highlights that Th2 cytokines potentiate TRP channels through diverse mechanisms under different inflammatory and pruritic conditions, and link this effect to distinct signaling cascades in AD. This review strengthens the notion that interrupting Th2-driven modulation of TRP channels will inhibit transition from acute to chronic AD, thereby aiding the development of effective therapeutics and treatment optimization.
Learn More >The fear-avoidance model provides an explanation for the development of chronic pain, including the role of perception (i.e. pain catastrophism) as an explanatory variable. Recent research has shown that the relationship between pain catastrophism and avoidance is influenced in turn by different psychological and contextual variables, highlighting the affective-motivational ones. From this perspective, the Goal Pursuit Questionnaire (GPQ) was developed to measure the preference for hedonic goals (mood-management or pain-avoidance goals) over achievement goals in musculoskeletal pain patients. Recently, the Spanish version of the GPQ in fibromyalgia patients has been validated. Our aim has been to adapt the Spanish version of GPQ from pain to fatigue symptoms and to validate this new questionnaire (GPQ-F) in fibromyalgia. Despite the recognition of fibromyalgia as a complex disorder and the need for a differential study of its symptoms, fatigue, despite its high prevalence and limiting nature, remains the forgotten symptom. We conducted a cross-sectional study with 231 women with fibromyalgia. Previously, we adapted the Spanish GPQ for fatigue symptoms with three sub-studies (group structured interview, self-administration questionnaire and thinking-aloud; n = 15-27 patients). We explored the GPQ structure and performed path analyses to test conditional mediation relationships. Exploratory factor analysis showed two factors: 'Fatigue-avoidance goal' and 'Mood-management goal' (39.3% and 13.9% of explained variance, respectively). The activity avoidance pattern fully mediated the relation between both catastrophizing and fatigue-avoidance goals with fatigue. The study shows initial findings about the usefulness of the GPQ-F as a tool to analyze goal preferences related to fatigue in fibromyalgia. The results supported the mediational role of activity avoidance patterns in the relationship between preference for fatigue-avoidance goals and fatigue.
Learn More >Contextual factors, such as participant/experimenter sex may moderate the placebo effects. We tested whether the participant and experimenter sex modulated placebo effects on experimentally induced pain and associated stress.
Learn More >Dissemination research is the study of distributing information and intervention materials to a specific clinical practice or public health audience. Acupuncture, a healthcare practice involving the stimulation of certain body points, often with thin needles, is considered an evidence-based treatment for low back pain (LBP), but is underutilized in the United States. We will use the example of acupuncture for LBP to identify opportunities to leverage dissemination research to increase utilization of acupuncture. Deficits in the awareness or knowledge of acupuncture may limit its adoption by patients and other stakeholders. Thus, we summarize methods to gather data on stakeholder awareness and knowledge of acupuncture for LBP, i.e., audience research. Engaging multiple stakeholder audiences (e.g., health system leaders, primary care providers, patients), is needed to generate knowledge on promising dissemination strategies for each audience. Audience segmentation is important for identifying population subgroups for whom adoption of acupuncture may require a more intensive or tailored dissemination strategy. To illustrate potential audience 'segments', our research discussion focused on developing dissemination strategies by age (i.e., older adults – those age 65 years or older, and younger adults – those under age 65 ). This decision was prompted by Medicare's recent policy covering acupuncture for chronic LBP. We leverage current knowledge of barriers and facilitators of acupuncture use to discuss how further tailoring of dissemination strategies might optimize adoption of acupuncture in both groups of adults. Experimental study designs could then be used to compare the effectiveness of such strategies to increase awareness, knowledge, or adoption of acupuncture. Conducting dissemination research may improve awareness and knowledge of acupuncture, and ultimately the adoption of acupuncture in biomedical settings. We anticipate that the concepts highlighted in this manuscript will also be helpful for those disseminating information about other complementary and integrative health approaches.
Learn More >To characterize the relationship between persistent post-traumatic headache (pPTH) and traumatic cerebrovascular injury (TCVI) in chronic traumatic brain injury (TBI). Cerebrovascular reactivity (CVR), a measure of the cerebral microvasculature and endothelial cell function, is altered both in individuals with chronic TBI and migraine headache disorder (Amyot et al., 2017; Lee et al., 2019b). The pathophysiologies of pPTH and migraine are believed to be associated with chronic microvascular dysfunction. We therefore hypothesize that TCVI may contribute to the underlying migraine-like mechanism(s) of pPTH.
Learn More >The COVID-19 pandemic called for drastic changes to expand and rapidly implement telehealth to prevent breach of care for chronic patients. Responding to the challenge of implementing remote care in chronic pain services, a specialty highly dependent on doctor-patient rapport, physical examination, and frequent follow-up visits requires extensive adaptation involving administrative processes and clinical routines. We present our experience of a successful rapid adaptation to telemedicine paradigm as a response to the COVID-19 pandemic during a time of marked restriction of access to ambulatory hospital services for pediatric and adult chronic pain patients. This narrative review covers current scientific evidence for the use of telehealth for chronic pain management and describes in detail the challenges to implement telemedicine in ambulatory clinics from different perspectives. Best practices for telehealth use are recommended. A proposal for remote physical examination of pain patients is made, based on available evidence in the fields of musculoskeletal medicine and neurology comparing in-person vs remote physical examination. As an internal quality control process, an informal online survey was conducted to assess thoughts and experiences among patients and caregivers using telemedicine consultation services at the pediatric pain clinic. Providing chronic pain management services through telehealth is a viable option for many patients and health care professionals. This is reliant on the availability of appropriate materials and training, with guidelines for both patients and health care workers. With the rapid pace of technological advancements, even further integration of telehealth into routine health care is possible.
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