CHOP‐Mediated Disruption of Hippocampal Synaptic Plasticity and Neuronal Activity Contributes to Chronic Pain‐Related Cognitive Deficits

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 1, 2025

ABSTRACT Objectives Endoplasmic reticulum (ER) stress‐induced protein homeostasis perturbation is a core pathological element in the pathogenesis of neurodegenerative diseases. This study aims to clarify unique role played by C/EBP homologous (CHOP) as biomarker unfolded response (UPR) etiology chronic pain and related cognitive impairments following constrictive nerve injury (CCI). Methods The memory capability CCI was assessed utilizing Morris water maze (MWM) fear conditioning test (FCT). Activation UPR quantified assessing levels CHOP key ER stress sensors. terminal deoxynucleotidyl transferase (TdT) dUTP nick‐end labeling (TUNEL) assay cleaved caspase‐3 were utilized assess apoptosis level. Synaptic plasticity via modified Golgi‐Cox staining method, long‐term potentiation (LTP) measurements taken. Neuronal activity determined immunofluorescence fiber photometry. Knockdown alleviation selectively induced LV‐Ddit3‐shRNAs chemical chaperone 4‐phenylbutyric acid (4‐PBA), respectively. Results Mice subjected displayed enduring evident on Days 21–28 post‐surgery. Following CCI, changes dorsal CA1 (dCA1) manifested dilation, upregulation upstream signaling molecules, reduced dendritic spine density, PSD95 levels, impaired LTP. Additionally, co‐localization CaMKIIα/c‐Fos CaMKIIα dCA1 ‐mediated calcium significantly reduced, while activation found mitigate mice. Selective knockdown enhanced synaptic neuron activity, 4‐PBA treatment alleviated stress, synergistically improving deficits associated with pain. Conclusion CCI‐induced impairs neuronal leading pain‐related deficits.

Language: Английский

---

Advancements and prospects of transcranial focused ultrasound in pain neuromodulation

Pain, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract Transcranial focused ultrasound (tFUS) is an emerging noninvasive neuromodulation technology that has shown great potential in pain modulation. This review systematically elucidates the multilevel biological mechanisms of tFUS neuromodulation, from network-wide effects to cellular and molecular processes, as well broader systemic influences. Preliminary animal model studies have revealed tFUS's ability improve behavioral indicators modulate neural circuit activity under pathological conditions. A small number clinical also suggest may certain benefits improving symptom experience emotional state chronic patients. However, current research generally limitations such sample sizes short follow-up periods. More high-quality are needed verify long-term safety treatment. Overcoming these advancing large-scale translational will help fully exploit application precision medicine provide new treatment options for relief.

Language: Английский

---

Sleep Disorders: Pathogenesis and Therapeutic Interventions

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

Sleep disorder significantly disrupts the quality of life for patients. Although it is clinically acknowledged, fundamental neuropathological mechanisms are still not understood. Recent preclinical research has been directed toward understanding underlying sleep deprivation and sleep/wake dysregulation. linked to changes in structure function neural basis cognition. We reviewed circuits related disorders, along with alterations connectivity brain region functions, based on advancements electrophysiology optogenetic/chemogenetic techniques. subsequently outline cellular molecular modifications disorders studies, primarily involving neuronal metabolism, electrophysiological activity, synaptic plasticity, glial cells. Correspondingly, crosstalk between peripheral organs, we elucidate involvement celiac disease hepatic pathogenesis disorders. In this review, mainly discussed at molecular, cellular, circuit levels that contribute disorder. The review also covered potential strategies treating future avenues.

Language: Английский

---

Longitudinal associations between pain and cognitive decline in middle-aged and older Chinese adults: the mediating role of depressive symptoms

Frontiers in Public Health, Journal Year: 2025, Volume and Issue: 13

Published: March 31, 2025

Objective The primary aim of this scholarly investigation was to elucidate the correlation between Number Pain Sites and cognitive decline within older adult population. Additionally, study sought examine potential mediating influence depressive symptoms in moderating association pain deterioration. Methods We analyzed 8,835 participants aged 45 above, with data collected from 2011 2018. Participants were categorized into two groups—stable rapidly declining function—using KML3D clustering method. Binary logistic regression analysis conducted status, symptoms, trajectories, mediation used assess role depression. Results Multi-site significantly associated risk rapid (adjusted OR = 1.30, 95% CI: 1.14–1.48), also a significant predictor 1.49, 1.32–1.68). Mediation revealed that depression mediated effect on decline, accounting for 25.71% total effect. Conclusion Our establishes longitudinal link part by symptoms. This finding underscores need interventions address potentially decelerate adults.

Language: Английский

---

Trajectories of pain and their associations with long-term cognitive decline in older adults: evidence from two longitudinal cohorts

Age and Ageing, Journal Year: 2024, Volume and Issue: 53(8)

Published: Aug. 1, 2024

Abstract Background Pain is a dynamic experience that varies over time, but it remains unknown whether trajectories of pain are associated with subsequent cognitive decline. The purpose this study was to identify distinct presence and activity-limiting investigate their longitudinal associations the rate decline in older adults. Methods A total 5685 participants from English Longitudinal Study Ageing (ELSA) 7619 Health Retirement (HRS) were included. identified eight years ELSA 10 HRS, while HRS. We utilised linear mixed-effects models long-term relationship between across various domains, including memory, orientation, executive function global cognition. Results Three identified. Moderate-increasing high-stable groups exhibited steeper declines cognition than low-stable group. Furthermore, individuals moderate-increasing group experienced more rapid function, showed faster orientation function. Two identified, experiencing Conclusions both linked among people. Interventions for specific might help delay domains.

Language: Английский

---

A Systematic Review on the Neuropsychological Assessment of Patients with LBP: The Impact of Chronic Pain on Quality of Life

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(20), P. 6149 - 6149

Published: Oct. 15, 2024

Low back pain (LBP) is most common syndrome in Europe, affecting approximately 50% of European citizens. LBP a complex condition that negatively affects many aspects an individual's life such as work productivity, mobility, and mental health. The aim this study to assess the impact associated with chronic on patients' quality life.

Language: Английский

---

Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding

Pain, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract Dysfunctional hyperactivity of the lateral habenula nucleus (LHb) has emerged as a critical marker for pain-related mood impairments. Acting central hub, LHb filters and disseminates pertinent information to other brain structures during learning. However, it is not well understood how intra-LHb activity altered cognitive demand under neuropathic pain conditions. To address this gap, we implanted an optrode structure record neuronal in adult male CD (rat strain without definition) rats execution delayed nonmatch-to-sample (DNMS) spatial working memory (WM) task. We selectively modulated network by optogenetically inhibiting local CaMKIIα (calcium calmodulin-dependent protein kinase II alpha)-expressing neurons delay phase DNMS Behavioral assessments were conducted using persistent rodent model pain—spared nerve injury. Our results showed that induction disrupted WM encoding accuracy functional connectivity. This disruption was reversed optogenetic inhibition CaMKIIα-expressing neurons, which also produced antinociceptive effects. Together, our findings provide insight into networks reorganize support different task contexts, suggesting abnormal dynamic segregation may contribute poor rodents experiences.

Language: Английский

---

The involvement of the dysfunctional insulin receptor signaling system in long COVID patients with diabetes and chronic pain and its implications for the clinical management using taVNS

Frontiers in Pain Research, Journal Year: 2024, Volume and Issue: 5

Published: Nov. 25, 2024

In clinical terms, chronic pain is the most prevalent sequela resulting from COVID-19, which induced by novel coronavirus (SARS-CoV-2), while type 2 diabetes mellitus (T2D) common comorbidity. This triangular relationship can be attributed to dysfunction of insulin receptor signaling system (IRSS) in both central and peripheral systems. Patients with T2D are essentially more susceptible SARS-CoV-2 infection due widespread expression angiotensin converting enzyme (ACE2) their pancreatic beta cells, serves as cellular port for infect enter cell. exacerbate resistance various reasons. Peripherally, once infected, virus cause damage nerves β-cells, further exacerbating glucose metabolism conditions. Additionally, nervous system, dysfunctional IRSS closely linked pain. Over past few years COVID-19 pandemic, an increasing body evidence suggests that other medications currently used practice hyperglycemia control may not safe treating these patients. Therefore, we need a proper approach treatment long COVID patients, especially patients T2D. review presents transcutaneous auricular vagal nerve stimulation (taVNS) provide viable option metabolic improving function tissues.

Language: Английский

---