IL-23/IL-17A/TRPV1 axis produces mechanical pain via macrophage-sensory neuron crosstalk in female mice

Neuron, Journal Year: 2021, Volume and Issue: 109(17), P. 2691 - 2706.e5

Published: July 19, 2021

Although sex dimorphism is increasingly recognized as an important factor in pain, female-specific pain signaling not well studied. Here we report that administration of IL-23 produces mechanical (mechanical allodynia) female but male mice, and chemotherapy-induced selectively impaired mice lacking Il23 or Il23r. IL-23-induced promoted by estrogen suppressed androgen, suggesting involvement hormones. requires C-fiber nociceptors TRPV1 to produce does directly activate nociceptor neurons. Notably, IL-17A release from macrophages evoke females. Low-dose activates induces only Finally, deletion receptor subunit α (ERα) TRPV1+ abolishes IL-23- IL-17-induced These findings demonstrate the IL-23/IL-17A/TRPV1 axis regulates via neuro-immune interactions. Our study also reveals at both immune neuronal levels.

Language: Английский

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Targeting Oxidative Stress Involved in Endometriosis and Its Pain

Biomolecules, Journal Year: 2022, Volume and Issue: 12(8), P. 1055 - 1055

Published: July 29, 2022

Endometriosis is a common gynecological disorder seen in women and characterized by chronic pelvic pain infertility. This becoming more prevalent with increased morbidity. The etiology of endometriosis remains to be fully elucidated, which will lead improved therapeutic options. In this review, we evaluate the biochemical mechanisms leading oxidative stress their implication pathophysiology endometriosis, as well potential treatments that target these processes. A comprehensive exploration previous research revealed associated elevated reactive oxygen species oxidation products, decreased antioxidants detoxification enzymes, dysregulated iron metabolism. High levels contributed inflammation, extracellular matrix degradation, angiogenesis, cell proliferation, may explain its role endometriosis. Endometriosis-associated was attributed neurogenic inflammation feed-forward mechanism involving macrophages, pro-inflammatory cytokines, pain-inducing prostaglandins. N-acetylcysteine, curcumin, melatonin, combined vitamin C E supplementation displayed promising results for treatment but further needed use population.

Language: Английский

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Multimodal control of dendritic cell functions by nociceptors

Science, Journal Year: 2023, Volume and Issue: 379(6639)

Published: March 31, 2023

It is known that interactions between nociceptors and dendritic cells (DCs) can modulate immune responses in barrier tissues. However, our understanding of the underlying communication frameworks remains rudimentary. Here, we show control DCs three molecularly distinct ways. First, release calcitonin gene-related peptide imparts a transcriptional profile on steady-state characterized by expression pro-interleukin-1β other genes implicated DC sentinel functions. Second, nociceptor activation induces contact-dependent calcium fluxes membrane depolarization enhances their production proinflammatory cytokines when stimulated. Finally, nociceptor-derived chemokine CCL2 contributes to orchestration DC-dependent local inflammation induction adaptive against skin-acquired antigens. Thus, combined actions chemokines, neuropeptides, electrical activity fine-tune

Language: Английский

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Inflammation in pathogenesis of chronic pain: Foe and friend

Molecular Pain, Journal Year: 2023, Volume and Issue: 19

Published: May 23, 2023

Chronic pain is a refractory health disease worldwide causing an enormous economic burden on individuals and society. Accumulating evidence suggests that inflammation in the peripheral nervous system (PNS) central (CNS) major factor pathogenesis of chronic pain. The early- late phase may have distinctive effects initiation resolution pain, which can be viewed as friend or foe. On one hand, painful injuries lead to activation glial cells immune PNS, releasing pro-inflammatory mediators, contribute sensitization nociceptors, leading pain; neuroinflammation CNS drives promotes development other macrophages PNS promote via anti-inflammatory mediators specialized pro-resolving (SPMs). In this review, we provide overview current understanding deterioration Further, summarize number novel strategies used prevent treat by controlling inflammation. This comprehensive view relationship between its specific mechanism will targets for treatment

Language: Английский

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The role of Toll‐like receptors in neuropsychiatric disorders: Immunopathology, treatment, and management

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 44(3), P. 1267 - 1325

Published: Jan. 16, 2024

Neuropsychiatric disorders denote a broad range of illnesses involving neurology and psychiatry. These include depressive disorders, anxiety, schizophrenia, bipolar disorder, attention deficit hyperactivity autism spectrum headaches, epilepsy. In addition to their main neuropathology that lies in the central nervous system (CNS), lately, studies have highlighted role immunity neuroinflammation neuropsychiatric disorders. Toll-like receptors (TLRs) are innate act as bridge between adaptive immune systems via adaptor proteins (e.g., MYD88) downstream elements; TLRs classified into 13 families involved normal function CNS. expression affects course is influenced during pharmacotherapy; For example, multiple normalized major disorder pharmacotherapy. Here, neuroimmunology, treatment, management discussed. We recommend longitudinal comparatively assess cell-type-specific illness progression, remission. Also, further research should explore molecular insights regulation related pathways.

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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Macrophage as a Peripheral Pain Regulator

Cells, Journal Year: 2021, Volume and Issue: 10(8), P. 1881 - 1881

Published: July 24, 2021

A neuroimmune crosstalk is involved in somatic and visceral pathological pain including inflammatory neuropathic components. Apart from microglia essential for spinal supraspinal processing, the interaction of bone marrow-derived infiltrating macrophages and/or tissue-resident with primary afferent neurons regulates signals peripheral tissue. Recent studies have uncovered previously unknown characteristics macrophages, such as their origins association regulation signals. Peripheral nerve intestinal resident addition to adult monocyte-derived secrete a variety mediators, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, high mobility group box 1 morphogenic protein 2 (BMP2), that regulate excitability afferents. Neuron-derived mediators neuropeptides, ATP macrophage-colony stimulating factor activity or polarization diverse macrophages. Thus, multitasks homeostatic conditions participate by interacting neurons.

Language: Английский

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Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy

The Journal of Headache and Pain, Journal Year: 2020, Volume and Issue: 21(1)

Published: Aug. 17, 2020

Neuropathic pain (NP) is a sustained and nonreversible condition characterized by long-term devastating physical psychological damage. Therefore, it urgent to identify an effective treatment for NP. Unfortunately, the precise pathogenesis of NP has not been elucidated. Currently, microbiota-gut-brain axis drawn increasing attention, emerging role gut microbiota investigated in numerous diseases including Gut considered as pivotal regulator immune, neural, endocrine, metabolic signaling pathways, which participates forming complex network affect development directly or indirectly. In this review, we conclude current understanding preclinical clinical findings regarding provide novel therapeutic method relief medication dietary interventions.

Language: Английский

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Dorsal Root Ganglia Macrophages Maintain Osteoarthritis Pain

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(39), P. 8249 - 8261

Published: Aug. 16, 2021

Pain is the major debilitating symptom of osteoarthritis (OA), which difficult to treat. In OA patients joint tissue damage only poorly associates with pain, indicating other mechanisms contribute pain. Immune cells regulate sensory system, but little known about involvement immune in Here, we report that macrophages accumulate dorsal root ganglia (DRG) distant from site injury two rodent models OA. DRG acquired an M1-like phenotype, and depletion resolved pain male female mice. Sensory neurons innervating damaged knee shape into phenotype. Persisting accumulation macrophages, programming phenotype were independent Na_v1.8 nociceptors. Inhibition by intrathecal injection IL4-IL10 fusion protein or M2-like persistent conclusion, these findings reveal a crucial role for maintaining suggest new direction treat SIGNIFICANCE STATEMENT correlates changes than cause We identified containing somata are infiltrated shaped neurons. show actively maintain remotely damage. The pain-promoting role. Targeting either cytokine skews resolves Our work reveals mechanism contributes maintenance affected suggests target chronic

Language: Английский

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Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: March 17, 2021

Abstract GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of in multiple models infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, the mouse malaria parasite Plasmodium berghei . Sepsis induced LPS wild-type mice is protected artesunate (ARU) neuroprotectin D1 (NPD1), actions these agents are lost −/− mice. Notably, found that ARU binds to macrophages promotes phagocytosis clearance pathogens. Moreover, ablation potentiated infection, sepsis, their sequelae, whereas adoptive transfer NPD1- or ARU-primed reduced pain-like behaviors. Our findings reveal physiological host cells activating suggest agonists may help treat bacterial infections, malaria.

Language: Английский

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