Browsing by Author "Knezevic, Nebojsa Nick (35302673900)"

Chronic stress significantly influences the pathogenesis of headache disorders, affecting millions worldwide. This review explores the intricate relationship between stress and headaches, focusing on the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS). Persistent stress could lead to neuroinflammation, increased pain sensitivity, and vascular changes that could contribute to headache development and progression. The bidirectional nature of this relationship creates a vicious cycle, with recurrent headaches becoming a source of additional stress. Dysregulation of the HPA axis and ANS imbalance could amplify susceptibility to headaches, intensifying their frequency and severity. While pharmacological interventions remain common, non-pharmacological approaches targeting stress reduction, such as cognitive-behavioral therapy, biofeedback, and relaxation techniques, offer promising avenues for comprehensive headache management. By addressing the underlying stress-related mechanisms, these approaches provide a sustainable strategy to reduce headache frequency and improve patients’ quality of life. © 2025 by the authors.

Chronic stress significantly influences the pathogenesis of headache disorders, affecting millions worldwide. This review explores the intricate relationship between stress and headaches, focusing on the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS). Persistent stress could lead to neuroinflammation, increased pain sensitivity, and vascular changes that could contribute to headache development and progression. The bidirectional nature of this relationship creates a vicious cycle, with recurrent headaches becoming a source of additional stress. Dysregulation of the HPA axis and ANS imbalance could amplify susceptibility to headaches, intensifying their frequency and severity. While pharmacological interventions remain common, non-pharmacological approaches targeting stress reduction, such as cognitive-behavioral therapy, biofeedback, and relaxation techniques, offer promising avenues for comprehensive headache management. By addressing the underlying stress-related mechanisms, these approaches provide a sustainable strategy to reduce headache frequency and improve patients’ quality of life. © 2025 by the authors.

[No abstract available]

Chronic stress is a significant factor affecting modern society, with profound implications for both physical and mental health. Central to the stress response is cortisol, a glucocorticoid hormone produced by the adrenal glands. While cortisol release is adaptive in acute stress, prolonged exposure to elevated levels can result in adverse effects. This manuscript explores the neurobiological implications of chronic stress and its impact on metabolic dysregulation, particularly in the context of inflammatory bowel diseases (IBDs). The hypothalamic–pituitary–adrenal (HPA) axis regulates cortisol production, which influences metabolism, immune response, and neurobiology. Elevated cortisol levels are associated with the development and exacerbation of metabolic disorders like IBD and contribute to neurodegenerative processes, including cognitive impairments and increased susceptibility to psychiatric conditions. The interaction between cortisol and its receptors, particularly glucocorticoid receptors, underscores the complexity of these effects. This review aims to elucidate the mechanisms through which chronic stress and cortisol dysregulation impact metabolic health and neurobiological function, providing insights into potential therapeutic strategies for mitigating these effects. © 2024 by the authors.

Introduction: Neuropathic pain (NP) remains a significant challenge in clinical practice, requiring a sophisticated pharmacotherapeutic strategy for effective symptom management. This review provides a comprehensive analysis of the current pharmacological treatments for NP, focusing on their efficacy, mechanism of action, and therapeutic potential. Additionally, it evaluates ongoing clinical trials investigating novel drugs and therapeutic approaches, highlighting emerging trends and future directions in NP management. Areas covered: This review examines first- to third-line therapeutic modalities for NP, critically analyzing their efficacy, safety profiles, and clinical applications. It also includes an overview of ongoing clinical trials exploring innovative pharmacological therapies. A thorough literature review was conducted using the MEDLINE database without temporal limitations, offering a detailed assessment of established and emerging treatments. Expert opinion: While current pharmacological options offer significant symptom relief, their overall effectiveness in managing NP remains limited, highlighting the need for further therapeutic advancements. Staying informed about emerging therapies and clinical trials is vital to enhancing patient care and quality of life. The future of NP management lies in optimizing individualized treatment strategies, refining therapeutic approaches, and fostering interdisciplinary collaboration. Close monitoring of outcomes and continued research are essential for advancing understanding and improving the precision of NP therapies. © 2025 Informa UK Limited, trading as Taylor & Francis Group.

Introduction: Neuropathic pain (NP) remains a significant challenge in clinical practice, requiring a sophisticated pharmacotherapeutic strategy for effective symptom management. This review provides a comprehensive analysis of the current pharmacological treatments for NP, focusing on their efficacy, mechanism of action, and therapeutic potential. Additionally, it evaluates ongoing clinical trials investigating novel drugs and therapeutic approaches, highlighting emerging trends and future directions in NP management. Areas covered: This review examines first- to third-line therapeutic modalities for NP, critically analyzing their efficacy, safety profiles, and clinical applications. It also includes an overview of ongoing clinical trials exploring innovative pharmacological therapies. A thorough literature review was conducted using the MEDLINE database without temporal limitations, offering a detailed assessment of established and emerging treatments. Expert opinion: While current pharmacological options offer significant symptom relief, their overall effectiveness in managing NP remains limited, highlighting the need for further therapeutic advancements. Staying informed about emerging therapies and clinical trials is vital to enhancing patient care and quality of life. The future of NP management lies in optimizing individualized treatment strategies, refining therapeutic approaches, and fostering interdisciplinary collaboration. Close monitoring of outcomes and continued research are essential for advancing understanding and improving the precision of NP therapies. © 2025 Informa UK Limited, trading as Taylor & Francis Group.

Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and cognitive or motor decline, often underpinned by pathological protein misfolding and aggregation. Emerging evidence suggests a potential mechanistic link between chronic pain and NDs, with persistent pain contributing to neuroinflammatory states and protein homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis that protein misfolding and aggregation serve as a mechanistic bridge between chronic pain and neurodegeneration. We systematically examine molecular pathways of protein misfolding, proteostasis dysfunction in chronic pain, and shared neuroimmune mechanisms, highlighting prion-like propagation of misfolded proteins, chronic neuroinflammation, and oxidative stress as common denominators. We further discuss evidence from experimental models and clinical studies linking chronic pain to accelerated neurodegenerative pathology—including tau accumulation, amyloid dysregulation, and microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting protein aggregation, enhancing chaperone function, modulating the unfolded protein response (UPR), and attenuating glial activation are explored as potential strategies to mitigate chronic pain and possibly slow neurodegeneration. Understanding this intersection not only elucidates chronic pain’s role in cognitive decline but also suggests that interventions addressing proteostasis and inflammation could yield dual benefits in pain management and neurodegenerative disease modification. © 2025 by the authors.

Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and cognitive or motor decline, often underpinned by pathological protein misfolding and aggregation. Emerging evidence suggests a potential mechanistic link between chronic pain and NDs, with persistent pain contributing to neuroinflammatory states and protein homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis that protein misfolding and aggregation serve as a mechanistic bridge between chronic pain and neurodegeneration. We systematically examine molecular pathways of protein misfolding, proteostasis dysfunction in chronic pain, and shared neuroimmune mechanisms, highlighting prion-like propagation of misfolded proteins, chronic neuroinflammation, and oxidative stress as common denominators. We further discuss evidence from experimental models and clinical studies linking chronic pain to accelerated neurodegenerative pathology—including tau accumulation, amyloid dysregulation, and microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting protein aggregation, enhancing chaperone function, modulating the unfolded protein response (UPR), and attenuating glial activation are explored as potential strategies to mitigate chronic pain and possibly slow neurodegeneration. Understanding this intersection not only elucidates chronic pain’s role in cognitive decline but also suggests that interventions addressing proteostasis and inflammation could yield dual benefits in pain management and neurodegenerative disease modification. © 2025 by the authors.

Obesity, chronic pain, and aging are prevalent global challenges with profound implications for health and well-being. Central to these processes are adrenal hormones, particularly cortisol and dehydroepiandrosterone (DHEA), along with its sulfated form (DHEAS). Cortisol, essential for stress adaptation, can have adverse effects on pain perception and aging when dysregulated, while DHEA/S possess properties that may mitigate these effects. This review explores the roles of cortisol and DHEA/S in the contexts of obesity, acute and chronic pain, aging, and age-related diseases. We examine the hormonal balance, specifically the cortisol-to-DHEA ratio (CDR), as a key marker of stress system functionality and its impact on pain sensitivity, neurodegeneration, and physical decline. Elevated CDR and decreased DHEA/S levels are associated with worsened outcomes, including increased frailty, immune dysfunction, and the progression of age-related conditions such as osteoporosis and Alzheimer’s disease. This review synthesizes the current literature to highlight the complex interplay between these hormones and their broader implications for health. It aims to provide insights into potential future therapies to improve pain management and promote healthy weight and aging. By investigating these mechanisms, this work contributes to a deeper understanding of the physiological intersections between pain, aging, and the endocrine system. © 2025 by the authors.