Pathology of pain and its implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 8, 2024

Abstract Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management crucial for individuals suffering from pain. However, current methods assessment treatment fall short clinical needs. Benefiting advances in neuroscience biotechnology, neuronal circuits molecular mechanisms critically involved modulation have been elucidated. These research achievements incited progress identifying new diagnostic therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting stage subsequent contents. The review next delves into underlying disorders, including gene mutation, epigenetic modification, posttranslational inflammasome, signaling pathways microbiota. To better present a comprehensive view research, two prominent issues, sexual dimorphism comorbidities, are discussed detail based on findings. status quo evaluation manipulation summarized. A series improved innovative strategies, such as therapy, monoclonal antibody, brain-computer interface microbial intervention, making strides towards application. We highlight existing limitations future directions enhancing quality preclinical research. Efforts decipher complexities pathology will be instrumental translating scientific discoveries practice, thereby improving bench bedside.

Language: Английский

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Tiam1 coordinates synaptic structural and functional plasticity underpinning the pathophysiology of neuropathic pain

Neuron, Journal Year: 2023, Volume and Issue: 111(13), P. 2038 - 2050.e6

Published: May 4, 2023

Language: Английский

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Chronic Pain and Comorbid Emotional Disorders: Neural Circuitry and Neuroimmunity Pathways

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 436 - 436

Published: Jan. 7, 2025

Chronic pain is a multidimensional experience that not only involves persistent nociception but also frequently accompanied by significant emotional disorders, such as anxiety and depression, which complicate its management amplify impact. This review provides an in-depth exploration of the neurobiological mechanisms underlying comorbidity chronic disturbances. Key areas focus include dysregulation major neurotransmitter systems (serotonin, gamma-aminobutyric acid, glutamate) resulting functional remodeling critical neural circuits implicated in processing, regulation, reward. Given contribution neuroimmune to chronicity mood we further conducted investigation into role factors, including resident immune cells, infiltrating release inflammatory mediators. discusses current therapeutic strategies, encompassing pharmacological interventions, neuromodulation, integrative approaches, emphasizes necessity targeted treatments address both components. Finally, it identifies gaps understanding outlines future research directions aimed at elucidating complex interplay between thereby laying foundation for more effective holistic treatment paradigms.

Language: Английский

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Lycopene Alleviates Depression‐Like Behavior in Chronic Social Defeat Stress‐Induced Mice by Promoting Synaptic Plasticity via the BDNF–TrkB Pathway

Food Science & Nutrition, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 1, 2025

ABSTRACT Lycopene is a natural plant extract widely studied for its powerful antioxidant and neuroprotective effects. Emerging evidence suggests that it also possesses potential antidepressant properties. Compared to commonly used clinical antidepressants, lycopene offers higher safety; however, underlying mechanisms remain unclear. Therefore, this study aims explore the through which exerts We employed chronic social defeat stress (CSDS) model induce depressive‐like behaviors in mice, followed by treatment (20 mg/kg). Based on previous research, we focused synaptic plasticity examining expression of proteins hippocampus uncover mechanisms. The results showed CSDS induced impairments but significantly improved these deficits reversed CSDS. Moreover, upregulated brain‐derived neurotrophic factor (BDNF) reduced activity BDNF–TrkB/pTrkB pathway hippocampus. These molecular changes were consistent with synaptic‐related proteins, suggesting may enhance via signaling pathway. This explored mice provided preclinical serve as antidepressant. It an effective avenue development novel therapies.

Language: Английский

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Esketamine reduces postoperative depression in breast cancer through TREK-1 channel inhibition and neurotransmitter modulation

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 18, 2025

Postoperative depression significantly affects the quality of life breast cancer patients. This study explores potential therapeutic effects esketamine on postoperative through modulation TREK-1 two-pore domain potassium channel. We analyzed data from 54 female patients who underwent surgery at our hospital between 2019 and 2023, dividing them into experimental control groups based treatment. Transcriptomic sequencing hippocampal neurons rats identified ion-related pathways key regulatory genes, including TREK-1, influenced by esketamine. In vitro studies showed that primarily alleviates depressive symptoms inhibiting protein expression, enhancing GABA neurotransmitter release, improving neuronal activity, while overexpression reversed these effects. Esketamine's inhibition channels promotion neuron activity effectively alleviate in patients, suggesting a novel strategy.

Language: Английский

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A nociceptive amygdala-striatal pathway for chronic pain aversion

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 13, 2024

The basolateral amygdala (BLA) is essential for assigning positive or negative valence to sensory stimuli. Noxious stimuli that cause pain are encoded by an ensemble of

Language: Английский

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Electroacupuncture promotes synaptic plasticity in rats with chronic inflammatory pain–related depression by upregulating BDNF/TrkB/CREB signaling pathway

Brain and Behavior, Journal Year: 2023, Volume and Issue: 13(12)

Published: Nov. 10, 2023

Chronic inflammatory pain (CIP) frequently coincides with depression among patients. The onset and development of are associated altered neural synaptic plasticity. Electroacupuncture (EA) can effectively relieve CIP depression. However, the underlying mechanisms have not been fully illustrated.

Language: Английский

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The mediating roles of depressive symptoms and social participation in the relationship between the effects of pain and cognitive function among Chinese older adults: A longitudinal study

Geriatric Nursing, Journal Year: 2024, Volume and Issue: 57, P. 147 - 153

Published: April 23, 2024

Language: Английский

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New perspective on sustained antidepressant effect: focus on neurexins regulating synaptic plasticity

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 1, 2024

Depression is highly prevalent globally, however, currently available medications face challenges such as low response rates and short duration of efficacy. Additionally, depression mostly accompany other psychiatric disorders, further progressing to major depressive disorder without long-term effective management. Thus, sustained antidepressant strategies are urgently needed. Recently, ketamine psilocybin gained attention potential antidepressants. Review recent studies highlights that synaptic plasticity changes key events downstream long-lasting in effect. This underscores the significance Moreover, neurexins, molecules involved regulation plasticity, act critical links between effects, involving mechanisms including protein level, selective splicing, epigenetics, astrocytes, positional redistribution structure. Based on by several drugs with for effect also discussed. Focusing neurexins regulating promises much understanding underlying next step new drug development. research represents a promising future direction.

Language: Английский

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Chronic Neuropathic Pain and Comorbid Depression Syndrome: From Neural Circuit Mechanisms to Treatment

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(13), P. 2432 - 2444

Published: June 25, 2024

Chronic neuropathic pain and comorbid depression syndrome (CDS) is a major worldwide health problem that affects the quality of life patients imposes tremendous socioeconomic burden. More than half with chronic also suffer from moderate or severe depression. Due to complex pathogenesis CDS, there are no effective therapeutic drugs available. The lack research on neural circuit mechanisms CDS limits development treatments. purpose this article provide an overview various circuits involved in CDS. Notably, activating some can alleviate and/or depression, while other exacerbate these conditions. Moreover, we discuss current emerging pharmacotherapies for such as ketamine. Understanding may clues novel drug treatments improved management.

Language: Английский

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