Acute inflammatory response via neutrophil activation protects against the development of chronic pain

Science Translational Medicine, Год журнала: 2022, Номер 14(644)

Опубликована: Май 11, 2022

The transition from acute to chronic pain is critically important but not well understood. Here, we investigated the pathophysiological mechanisms underlying low back (LBP) and performed transcriptome-wide analysis in peripheral immune cells of 98 participants with LBP, followed for 3 months. Transcriptomic changes were compared between patients whose LBP was resolved at months those persisted. We found thousands dynamic transcriptional over none persistent pain. Transient neutrophil-driven up-regulation inflammatory responses protective against In mouse assays, early treatment a steroid or nonsteroidal anti-inflammatory drug (NSAID) also led prolonged despite being analgesic short term; such prolongation observed other analgesics. Depletion neutrophils delayed resolution mice, whereas injection themselves, S100A8/A9 proteins normally released by neutrophils, prevented development long-lasting induced an drug. Analysis trajectories human subjects reporting UK Biobank identified elevated risk persistence taking NSAIDs. Thus, efficacy time points, management inflammation may be counterproductive long-term outcomes sufferers.

Язык: Английский

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Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape

American Journal of Psychiatry, Год журнала: 2023, Номер 180(3), С. 190 - 199

Опубликована: Март 1, 2023

One in three adults with major depressive disorder (MDD) do not experience clinically significant improvement after multiple sequential courses of antidepressants and have treatment-resistant depression (TRD). The presence TRD contributes to the morbidity excess mortality associated MDD has been linked significantly increased health care expenses. In absence a consensus definition TRD, this report takes broad approach by considering inadequate response one or more focuses on atypical antipsychotics that are approved U.S. Food Drug Administration for treatment (aripiprazole, brexpiprazole, cariprazine, extended-release quetiapine, olanzapine-fluoxetine combination). While acute-phase studies demonstrated efficacy these medications improving symptoms, meaningful (i.e., remission) remains limited, concerns about side effects (including weight gain, metabolic dysfunction, extrapyramidal tardive dyskinesia), especially long-term use. With rapidly evolving landscape antidepressant treatments over past few years, which witnessed approval rapid-acting (e.g., esketamine nasal spray dextromethorphan-bupropion combination) several late-stage pipeline zuranolone psilocybin), it be seen whether use will go way older rarely prescribed (such as tricyclics monoamine oxidase inhibitors). Pragmatic clinical trials needed compare effectiveness TRD-specific pharmacotherapies neuromodulation identify optimal sequencing varied approaches patients MDD. When using antipsychotics, clinicians encouraged shared decision-making personalizing selection based anticipated effects, tolerability, cost, feasibility.

Язык: Английский

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Neural correlates of co-occurring pain and depression: an activation-likelihood estimation (ALE) meta-analysis and systematic review

Translational Psychiatry, Год журнала: 2022, Номер 12(1)

Опубликована: Май 11, 2022

Abstract The relationship between pain and depression is thought to be bidirectional the underlying neurobiology ‘shared’ two conditions. However, these claims are often based on qualitative comparisons of brain regions implicated in or depression, while focused quantitative studies pain-depression comorbidity lacking. Particularly, direction comorbidity, i.e., with vs. pain, rarely addressed. In this systematic review (PROSPERO registration CRD42020219876), we aimed delineate correlates associated primary concomitant concurrent equal using activation likelihood estimation (ALE) meta-analysis. Neuroimaging published English until 28th September 2021 were evaluated PRISMA guidelines. A total 70 included, which 26 reported stereotactic coordinates analysed ALE. All assessed for quality by authors, National Institute Health Quality Assessment Tool. Our results revealed paucity that directly investigated comorbidity. ALE analysis indicated was right amygdala, related primarily left dorsolateral prefrontal cortex (DLPFC). We provide evidence have a cumulative negative effect specific set regions, distinct diagnosis pain.

Язык: Английский

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Neuropathic pain, mood, and stress-related disorders: A literature review of comorbidity and co-pathogenesis

Neuroscience & Biobehavioral Reviews, Год журнала: 2024, Номер 161, С. 105673 - 105673

Опубликована: Апрель 16, 2024

Язык: Английский

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Insula?Amygdala and Insula?Thalamus Pathways Are Involved in Comorbid Chronic Pain and Depression-Like Behavior in Mice

Journal of Neuroscience, Год журнала: 2024, Номер 44(15), С. e2062232024 - e2062232024

Опубликована: Март 7, 2024

The comorbidity of chronic pain and depression poses tremendous challenges for the treatment either one because they exacerbate each other with unknown mechanisms. As posterior insular cortex (PIC) integrates multiple somatosensory emotional information is implicated in or depression, we hypothesize that PIC its projections may contribute to pathophysiology comorbid depression. We show neurons were readily activated by mechanical, thermal, aversive, stressful appetitive stimulation naive neuropathic male mice subjected spared nerve injury (SNI). Optogenetic activation induced hyperalgesia conditioned place aversion mice, whereas inhibition these led analgesia, preference (CPP), antidepressant effect both SNI mice. Combining neuronal tracing, optogenetics, electrophysiological techniques, found monosynaptic glutamatergic from basolateral amygdala (BLA) ventromedial nucleus (VM) thalamus mimicked modulation mice; enhanced accompanied hyperactivity PIC, BLA, VM CPP, antidepressant-like effect. present study suggests potentiation PIC→BLA PIC→VM be important pathophysiological bases depression-like behavior reversing a promising therapeutic strategy

Язык: Английский

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Mental Health Challenges in Cancer Patients: A Cross-Sectional Analysis of Depression and Anxiety

Cancers, Год журнала: 2024, Номер 16(16), С. 2827 - 2827

Опубликована: Авг. 12, 2024

Advancements in cancer treatment and early detection have extended survival rates, transforming many cancers into chronic conditions. However, diagnosis can trigger significant psychological distress, including depression anxiety, impacting patient outcomes care. This study aimed to examine the prevalence of identify risk factors for anxiety among patients. A cross-sectional was conducted, patients under care oncology department at a tertiary medical center between June 2021 October 2023. Depression were assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) short forms. Logistic regression analysis identified anxiety. The population included 159 patients, with 40.3% reporting worsening mental health, but only about half them received therapy. Among participants, 22.6% experienced symptoms 30.2% Single-cancer those metastases increased depression, while disease duration more than year female-specific likely experience Given high health deterioration closer monitoring validated assessment tools are essential improve facilitate interventions.

Язык: Английский

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Does Low Grade Systemic Inflammation Have a Role in Chronic Pain?

Frontiers in Molecular Neuroscience, Год журнала: 2021, Номер 14

Опубликована: Ноя. 10, 2021

One of the major clinical manifestations peripheral neuropathy, either resulting from trauma or diseases, is chronic pain. While it significantly impacts patients’ quality life, underlying mechanisms remain elusive, and treatment not satisfactory. Systemic inflammation (SCI) that we are referring to in this perspective a state low-grade, persistent, non-infective inflammation, being found many physiological pathological conditions. Distinct acute which protective process fighting against intruders, SCI might have harmful effects. It has been associated with non-communicable diseases. We hypothesize could be predisposing and/or precipitating factor development pain, as well comorbidities. reviewed evidence human studies indicating coexistence various types also collated existing data about sources who it, showing those individuals patients having usually higher prevalence pain psychological thus elaborate on need for further research connection between Several hypotheses proposed explain these complex interactions.

Язык: Английский

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Impact of CYP2C19 metaboliser status on SSRI response: a retrospective study of 9500 participants of the Australian Genetics of Depression Study

The Pharmacogenomics Journal, Год журнала: 2022, Номер 22(2), С. 130 - 135

Опубликована: Янв. 29, 2022

Variation within the CYP2C19 gene has been linked to differential metabolism of selective serotonin reuptake inhibitors (SSRIs). Pharmacogenetic recommendations based on effect variants have made available and are used increasingly by clinical practitioners. Nonetheless, underlying assumption linking efficacy or adverse side effects remains understudied. Here, we aim fill this gap studying polymorphisms inferred patient-reported antidepressant response in a sample 9531 Australian adults who taken SSRIs.

Язык: Английский

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Alterations of monoamine neurotransmitters, HPA-axis hormones, and inflammation cytokines in reserpine-induced hyperalgesia and depression comorbidity rat model

BMC Psychiatry, Год журнала: 2022, Номер 22(1)

Опубликована: Июнь 22, 2022

Abstract Background Pain and depression often occur simultaneously, but the mechanism of this condition is still unclear. Methods The aim study was to examine alterations monoamine neurotransmitters, hypothalamic–pituitary–adrenal (HPA) axis hormones, inflammation cytokines in hyperalgesia comorbidities. reserpine-induced “Sprague Dawley” (SD) rat models were used, concentrations neurotransmitters serotonin (5-HT), norepinephrine (NE), dopamine (DA), their metabolic products 5-hydroxyindoleacetic acid (5-HIAA), Homovanillic (HVA), 3,4-Dihydroxyphenylacetic (DOPAC) raphe nucleus region tested by High Performance Liquid Chromatography (HPLC). Serum levels Adrenocorticotropic Hormone (ACTH), Cortisol (CORT), inflammatory interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-4, IL-10 assessed enzyme linked immunosorbent assay. Results Repeated reserpine injection induced depressive behaviors with decreased sucrose preference horizontal movement distance, increased immobility time forced swimming test. 5-HT NE nucleus, ACTH CORT serum elevated model group. And group showed increases IL-1β decrease IL-10. Conclusion More research these areas needed understand pathogenesis disease, so as find more better therapeutic targets.

Язык: Английский

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Electro-acupuncture inhibits HDAC2 via modulating gut microbiota to ameliorate SNI-induced pain and depression-like behavior in rats

Journal of Affective Disorders, Год журнала: 2024, Номер 360, С. 305 - 313

Опубликована: Фев. 21, 2024

Язык: Английский

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