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Persistent pain has been recently suggested as a risk factor for dementia. Indeed, chronic pain is frequently accompanied by maladaptive brain plasticity and cognitive deficits whose molecular underpinnings are poorly understood. Despite the emerging role of Tau as a key regulator of neuronal plasticity and pathology in diverse brain disorders, the role of Tau has never been studied in the context of chronic pain. Using a peripheral (sciatic) neuropathy to model chronic pain in mice-spared nerve injury (SNI) for 4 months-in wildtype as well as P301L-Tau transgenic mice, we hereby demonstrate that SNI triggers AD-related neuropathology characterized by Tau hyperphosphorylation, accumulation, and aggregation in hippocampus followed by neuronal atrophy and memory deficits. Molecular analysis suggests that SNI inhibits autophagy and reduces levels of the Rab35, a regulator of Tau degradation while overexpression of Rab35 or treatment with the analgesic drug gabapentin reverted the above molecular changes leading to neurostructural and memory recovery. Interestingly, genetic ablation of Tau blocks the establishment of SNI-induced hippocampal morphofunctional deficits supporting the mediating role of Tau in SNI-evoked hippocampal pathology and memory impairment. These findings reveal that exposure to chronic pain triggers Tau-related neuropathology and may be relevant for understanding how chronic pain precipitates memory loss leading to dementia.
Learn More >Elevated depressive symptoms are observed in a significant number of youth with inflammatory bowel disease (IBD) and have been linked to illness stigma and social isolation. Body image dissatisfaction is an understudied variable in the pediatric IBD literature that may be related to both stigma and social difficulties. It is suspected that, due to the stigmatizing nature of IBD, some youth may feel self-conscious about their body image, which contributes to decreased feelings of social belongingness and ultimately depressive symptoms. The current study tested an illness stigma→ body image dissatisfaction→ thwarted belongingness→ depressive symptoms serial mediation model, in which IBD stigma was hypothesized to indirectly influence youth depressive symptoms through the sequential effects of stigma on body image dissatisfaction and thwarted social belongingness.
Learn More >The incidence of chronic and recurrent pain increases in adolescence. Prevalence of adolescent chronic pain is estimated to be 11%-44%, with approximately 5% adolescents experiencing moderate-to-severe chronic pain. Adolescents with chronic pain also report unwanted changes in emotional, social, and developmental functioning. Very little is known about how adolescents with chronic pain make sense of their development, the role of pain in that development, and how such developmental trajectories progress over time. A multi-methods qualitative study was designed to explore how adolescents make sense of their experience of chronic pain in the context of development. Nine adolescents (8 girls) aged 12-22 years old (Mean = 15.7, SD = 2.8) were recruited from a UK national pain service. Adolescents completed an interview on entering the service, and a follow-up interview 12 months later. They also completed monthly diaries in this 12-month period. Data comprised 18 interviews and 60 diary entries, which were analyzed using inductive reflexive thematic analysis. Analyses generated one overarching theme entitled "tug of war: push and pull," demonstrating developmental tension related to pain, and the cumulative impact these had over time. This overarching theme comprised two subthemes which capture these tensions across the developmental domains of peer relationships and autonomy. The first subtheme, "the shifting sands of peer relationships," explores the ever-changing closeness between self and peers. The second subtheme referred to "restricted choices" and how pain limited the participants' autonomy but that this, over time could push development forward. These results extend previous cross-sectional research on the developmental consequences of chronic pain, showing the dynamic fluctuations and alterations to developmental trajectories over time.
Learn More >Kratom is the common term for Mitragyna speciosa and its products. Its major active compounds are mitragynine and 7-hydroxymitragynine. An estimated 2.1 million US residents used kratom in 2020, as a "legal high" and self-medication for pain, opioid withdrawal, and other conditions. Up to 20% of US kratom users report symptoms consistent with kratom use disorder. Kratom use is associated with medical toxicity and death. Causality is difficult to prove as almost all cases involve other psychoactive substances. Daily, high-dose use may result in kratom use disorder and opioid-like withdrawal on cessation of use. These are best treated with buprenorphine.
Learn More >Pain is a common symptom in patients with advanced, metastatic, or terminal cancer. Neuropathic pain and psycho-emotional suffering are factors that increase the difficulty of pain management. Pain control in patients with cancer remains a challenge for medical professionals.
Learn More >Patients with chronic knee pain are often unaware of treatment options and likely outcomes-information that is critical to decision-making. A consistent framework for communicating patient-personalized information enables clinicians to provide consistent, targeted, and relevant information. Our objective was to user-test a shared decision-making (SDM) tool for chronic knee pain.
Learn More >Pain control in trauma is an integral part of treatment in combat casualty care. More soldiers injured on the battlefield need analgesics for pain than life-saving interventions (LSIs). Early treatment of pain improves outcomes after injury, while inadequate treatment leads to higher rates of post-traumatic stress disorder (PTSD).
Learn More >Osteoarthritis (OA) is a leading cause of disability, the most common form of chronic disease in the temporomandibular joint (TMJ), and the most severe disease type of temporomandibular disorders (TMD). The etiology of TMD is multifactorial, considering parafunctional habits, sleep bruxism, or sleep disturbance as common factors. Insomnia and apnea are the two most frequent forms of sleep disorders in TMD patients. Due to this, the objective of this systematic review was to highlight whether there is currently scientific evidence in the literature describing that patients with temporomandibular joint osteoarthritis (TMJ-OA) are associated with increased sleep disorders or impaired sleep quality.
Learn More >Migraine is a complex neurovascular disorder characterized by recurrent attacks of pain and other associated symptoms. Emotional-affective aspects are important components of pain, but so far they have been little explored in animal models of migraine. In this study, we aimed to explore the correlation between trigeminal hyperalgesia and affective status or behavioral components in a migraine-specific animal model. Male Sprague-Dawley rats were treated with nitroglycerin (10 mg/kg, i.p.) or its vehicle. Four hours later, anxiety, motor/exploratory behavior and grooming (a nociception index) were evaluated with the open field test. Rats were then exposed to formalin in the orofacial region to evaluate trigeminal hyperalgesia. The data analysis shows an inverse correlation between trigeminal hyperalgesia and motor or exploratory behavior, and a positive association with anxiety-like behavior or self-grooming. These findings further expand on the translational value of the migraine-specific model based on nitroglycerin administration and prompt additional parameters that can be investigated to explore migraine disease in its complexity.
Learn More >Chronic pain is associated with reduced work participation, but longitudinal data on the work impact of chronic pain are limited. We used data from the National Longitudinal Survey of Youth-1997 cohort to analyze how pain interference in early adulthood was associated with subsequent exit from the labor force in a longitudinal survey. Pain interference at age 29 and employment status were self-reported at subsequent biennial interviews. Exit from the labor force, return to employment, and development of new health-related work limitations after age 29 were analyzed using survival analysis methods. Among 5,819 respondents, 10% and 3% endorsed "a little" or "a lot" of pain interference at age 29, respectively. During follow-up (median of 26 months until censoring or labor force exit), 43% of respondents had exited the labor force at least once, and 10% developed a new work-related health limitation. The highest pain interference group (compared to no pain interference) had higher hazard of labor force exit (hazard ratio, HR: 1.26; 95% confidence interval, CI: 1.01, 1.57; p=0.044) and of developing new health-related work limitations (HR: 2.45; 95% CI: 1.64, 3.67; p<0.001), with similar results for the group experiencing "a little" pain interference at age 29. In this nationally representative cohort, any level of pain interference reported at age 29 was found to predict increased hazards of subsequent labor force exit and health-related work limitation. Early identification and treatment of pain problems among young workers can help reduce burdens of future unemployment and disability.
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