Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain DOI Creative Commons

Sebastian Parusel,

Min‐Hee Yi, Christine Hunt

et al.

Neuroscience Bulletin, Journal Year: 2022, Volume and Issue: 39(3), P. 368 - 378

Published: Aug. 17, 2022

Abstract Chronic pain relief remains an unmet medical need. Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis. Particularly, microglia play crucial role the development chronic pain. To better understand microglial pain, specific regional and temporal manipulations are necessary. Recently, two new approaches have emerged that meet these demands. Chemogenetic tools allow expression designer receptors exclusively activated by drugs (DREADDs) specifically microglia. Similarly, optogenetic for manipulation via activation artificially expressed, light-sensitive proteins. Chemo- vivo powerful interrogating function This review summarizes emerging studying highlights their potential applications microglia-related neurological disorders.

Language: Английский

Pain-resolving immune mechanisms in neuropathic pain DOI
Nathan T. Fiore, Sophie R. Debs, Jessica P. Hayes

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: unknown

Published: March 1, 2023

Language: Английский

Citations

111
Neuropathic Pain: Mechanisms, Sex Differences, and Potential Therapies for a Global Problem DOI Creative Commons
Shahrzad Ghazisaeidi, Milind M. Muley, Michael W. Salter

et al.

The Annual Review of Pharmacology and Toxicology, Journal Year: 2023, Volume and Issue: 63(1), P. 565 - 583

Published: Jan. 20, 2023

The study of chronic pain continues to generate ever-increasing numbers publications, but safe and efficacious treatments for remain elusive. Recognition sex-specific mechanisms underlying has resulted in a surge studies that include both sexes. A predominant focus been on identifying sex differences, yet many newly identified cellular alterations gene expression are conserved between the Here we review differences similarities molecular signals drive generation resolution neuropathic pain. mix reflects degeneracy peripheral central signaling processes by which neurons, immune cells, glia codependently hypersensitivity. Recent findings critical nodes foreshadow development rationally designed, broadly applicable analgesic strategies. However, paucity effective, compels targeted therapies as well increase therapeutic options help reduce global burden suffering.

Language: Английский

Citations

99
Neuroimmune mechanisms and therapies mediating post-ischaemic brain injury and repair DOI
Takashi Shichita, Hiroaki Ooboshi, Akihiko Yoshimura

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(5), P. 299 - 312

Published: March 27, 2023

Language: Английский

Citations

61
Inflammation in pathogenesis of chronic pain: Foe and friend DOI Creative Commons

Xiao-Xia Fang,

Meng-Nan Zhai,

Meixuan Zhu

et al.

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

Citations

57
Mesenchymal stem cells in the treatment of spinal cord injury: Mechanisms, current advances and future challenges DOI Creative Commons

Yuanliang Xia,

Jianshu Zhu,

Ruohan Yang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 24, 2023

Spinal cord injury (SCI) has considerable impact on patient physical, mental, and financial health. Secondary SCI is associated with inflammation, vascular destruction, subsequent permanent damage to the nervous system. Mesenchymal stem cells (MSCs) have anti-inflammatory properties, promoting regeneration release neuro-nutrients, are a promising strategy for treatment of SCI. Preclinical studies shown that MSCs promote sensory motor function recovery in rats. In clinical trials, been reported improve American Injury Association (ASIA) scores. However, effectiveness treating patients remains controversial. tumorigenesis ensuring survival hostile environment challenging. this article we examine evidence pathophysiological changes occurring after We then review underlying mechanisms summarize potential application practice. Finally, highlight challenges surrounding use discuss future applications.

Language: Английский

Citations

54
A richer and more diverse future for microglia phenotypes DOI Creative Commons
Jie Wang,

Wen‐Bin He,

Junlong Zhang

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 9(4), P. e14713 - e14713

Published: March 21, 2023

Microglia are the only resident innate immune cells derived from mesoderm in nerve tissue. They play a role development and maturation of central nervous system (CNS). mediate repair CNS injury participate endogenous response induced by various diseases exerting neuroprotective or neurotoxic effects. Traditionally, microglia considered to be resting state, M0 type, under physiological conditions. In this they perform surveillance constantly monitoring pathological responses CNS. undergo series morphological functional changes state eventually polarize into classically activated (M1) alternatively (M2). M1 release inflammatory factors toxic substances inhibit pathogens, while M2 exert effects promoting regeneration. However, recent years, view regarding M1/M2 polarization has gradually changed. According some researchers, phenomenon is not yet confirmed. The term used for simplified description its phenotype function. Other researchers believe that process rich diverse, consequently, classification method limitations. This conflict hinders academic community establishing more meaningful pathways terms, therefore, careful revision concept required. present article briefly reviews current consensus controversy microglial typing provide supporting materials objective understanding microglia.

Language: Английский

Citations

54
Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury DOI Creative Commons

Yangning Lan,

Xiaoxuan Zhang, Shaorui Liu

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(2), P. 349 - 363.e9

Published: Feb. 1, 2024

Language: Английский

Citations

35
Sex differences in mechanisms of pain hypersensitivity DOI Creative Commons
Jeffrey S. Mogil, Marc Parisien,

Sahel Jahangiri Esfahani

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 163, P. 105749 - 105749

Published: June 3, 2024

The introduction of sex-as-a-biological-variable policies at funding agencies around the world has led to an explosion very recent observations sex differences in biology underlying pain. This review considers evidence sexually dimorphic mechanisms mediating pain hypersensitivity, derived from modern assays persistent rodent animal models. Three well-studied findings are described detail: male-specific role spinal cord microglia, female-specific calcitonin gene-related peptide (CGRP), and prolactin its receptor. Other sex-specific molecular involvement subjected pathway analyses reveal least one novel hypothesis: that females may preferentially use Th1 males Th2 T cell activity mediate chronic

Language: Английский

Citations

23
Divergent sex-specific pannexin-1 mechanisms in microglia and T cells underlie neuropathic pain DOI
Churmy Y. Fan, Brendan B. McAllister, Sierra Stokes-Heck

et al.

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

Published: Jan. 1, 2025

Language: Английский

Citations

3
Noteworthy perspectives on microglia in neuropsychiatric disorders DOI Creative Commons
Hongrui Zhu,

Ao Guan,

Jiayuan Liu

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Oct. 4, 2023

Abstract Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood–brain barrier architecture, and intriguingly, the regulation of emotions behaviors. have a profound impact on neuronal survival, wiring synaptic plasticity. As professional phagocytic cells brain, remove dead cell debris neurotoxic agents via an elaborate mechanism. The functional profile microglia varies considerately depending age, gender, disease context other internal or external environmental factors. Numerous studies demonstrated pivotal involvement neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain symptoms associated with major depression disorder, anxiety autism spectrum disorder schizophrenia. In this review, we summarized latest discoveries regarding microglial ontogeny, subtypes state spectrum, biological functions mechanistic underpinnings emotional behavioral disorders. Furthermore, highlight potential microglia-targeted therapies propose outstanding questions to be addressed future research human microglia.

Language: Английский

Citations

42