Spinal microglia-neuron interactions in chronic pain

Ho, Idy H. T.; Chan, Matthew T. V.; Wu, William Ka Kei; Liu, Xiao Dong

doi:10.1002/jlb.3mr0520-695r

Cited by 37 publications

(25 citation statements)

References 158 publications

(284 reference statements)

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“…The physiology of nociception and pathophysiology of chronic pain include peripheral and central structural and functional neuronal alterations as well as neuro-immune interactions, which become more prominent during inflammatory reactions [67]. Research over the past decades has increasingly detailed the brain’s capacity for reorganization of structural and functional neural network architecture to adapt to environmental needs.…”

Section: Pain Pathophysiologymentioning

confidence: 99%

Chronic Pain and the Endocannabinoid System: Smart Lipids – A Novel Therapeutic Option?

Zieglgänsberger

Brenneisen

Berthele³

et al. 2022

Med Cannabis Cannabinoids

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The development of a high-end cannabinoid-based therapy is the result of intense translational research, aiming to convert recent discoveries in the laboratory into better treatments for patients. Novel compounds and new regimes for drug treatment are emerging. Given that previously unreported signaling mechanisms for cannabinoids have been uncovered, clinical studies detailing their high therapeutic potential are mandatory. The advent of novel genomic, optogenetic, and viral tracing and imaging techniques will help to further detail therapeutically relevant functional and structural features. An evolutionarily highly conserved group of neuromodulatory lipids, their receptors, and anabolic and catabolic enzymes are involved in a remarkable variety of physiological and pathological processes and has been termed the endocannabinoid system (ECS). A large body of data has emerged in recent years, pointing to a crucial role of this system in the regulation of the behavioral domains of acquired fear, anxiety, and stress-coping. Besides neurons, also glia cells and components of the immune system can differentially fine-tune patterns of neuronal activity. Dysregulation of ECS signaling can lead to a lowering of stress resilience and increased incidence of psychiatric disorders. Chronic pain may be understood as a disease process evoked by fear-conditioned nociceptive input and appears as the dark side of neuronal plasticity. By taking a toll on every part of your life, this abnormal persistent memory of an aversive state can be more damaging than its initial experience. All strategies for the treatment of chronic pain conditions must consider stress-related comorbid conditions since cognitive factors such as beliefs, expectations, and prior experience (memory of pain) are key modulators of the perception of pain. The anxiolytic and anti-stress effects of medical cannabinoids can substantially modulate the efficacy and tolerability of therapeutic interventions and will help to pave the way to a successful multimodal therapy. Why some individuals are more susceptible to the effects of stress remains to be uncovered. The development of personalized prevention or treatment strategies for anxiety and depression related to chronic pain must also consider gender differences. An emotional basis of chronic pain opens a new horizon of opportunities for developing treatment strategies beyond the repeated sole use of acutely acting analgesics. A phase I trial to determine the pharmacokinetics, psychotropic effects, and safety profile of a novel nanoparticle-based cannabinoid spray for oromucosal delivery highlights a remarkable innovation in galenic technology and urges clinical studies further detailing the huge therapeutic potential of medical cannabis (Lorenzl et al.; this issue).

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Section: Pain Pathophysiologymentioning

confidence: 99%

Chronic Pain and the Endocannabinoid System: Smart Lipids – A Novel Therapeutic Option?

Zieglgänsberger

Brenneisen

Berthele³

et al. 2022

Med Cannabis Cannabinoids

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“…Microglia can directly influence neuronal activity and neuroplasticity through many signals [ 63 , 126 ] ( Figure 4 ). Interactions between microglia and neurons play an important role in many neurological disorders with altered neural network excitability [ 127 ].…”

Section: Molecular Pathways Underlying Exercise-induced Astrocyte Crosstalkmentioning

confidence: 99%

Neuroplastic Effect of Exercise Through Astrocytes Activation and Cellular Crosstalk

Li¹,

Xu²,

Yun³

et al. 2021

Aging and disease

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Physical exercise is an effective therapy for neurorehabilitation. Exercise has been shown to induce remodeling and proliferation of astrocyte. Astrocytes potentially affect the recruitment and function of neurons; they could intensify responses of neurons and bring more neurons for the process of neuroplasticity. Interactions between astrocytes, microglia and neurons modulate neuroplasticity and, subsequently, neural circuit function. These cellular interactions promote the number and function of synapses, neurogenesis, and cerebrovascular remodeling. However, the roles and crosstalk of astrocytes with neurons and microglia and any subsequent neuroplastic effects have not been studied extensively in exercise-induced settings. This article discusses the impact of physical exercise on astrocyte proliferation and highlights the interplay between astrocytes, microglia and neurons. The crosstalk between these cells may enhance neuroplasticity, leading to the neuroplastic effects of exercise.

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“…Microglial cells are important glial cells in the spinal cord that are responsible for the sensitization and maintenance of chronic pain (Ho et al 2020). Cortical and spinal microglia are crucial immunological constituents of the CNS that exert key functions in governing inflammatory responses in a variety of CNS disorders (Matsuura et al 2012).…”

Section: Introductionmentioning

confidence: 99%

β-elemene relieves neuropathic pain in mice through the regulation on C-X-C motif chemokine receptor 3 and GABAA receptor

Dai

Zeng

Deng

et al. 2022

Can. J. Physiol. Pharmacol.

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β-elemene (Bel) is a sesquiterpene compound has shown potential in the antinociceptive treatment. This study focused on the function of Bel in neuropathic pain relief in mice. A murine model with spared nerve injury (SNI) was established and treated with Bel. The paw withdrawal thresholds in response to mechanical and thermal stimulations were examined using von Frey filaments. The L4-L6 spinal dorsal horn tissue samples were collected for histological examination. Bel treatment reduced the sensitivities of model mice to mechanical and thermal stimulations, and it inhibited activation of microglia and the secretion of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in tissues. Bel treatment reduced the expression of nociceptor excitatory NMDAR whereas enhanced the expression of nociceptor inhibitory GABAA receptor to relieve the nociception of mice. CXCR3 was a downstream molecule mediated by Bel. Either overexpression of CXCR3 or downregulation of GABAA receptor in the tissues aggravated the neuropathic pain in SNI mice which was initially relieved by Bel. In conclusion, this study suggested that Bel might serve as a drug for nociception management by inhibiting CXCR3 and upregulating GABAA receptor. This study may offer novel insights into the field of neuropathic pain relief.

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Spinal microglia-neuron interactions in chronic pain

Cited by 37 publications

References 158 publications

Chronic Pain and the Endocannabinoid System: Smart Lipids – A Novel Therapeutic Option?

Chronic Pain and the Endocannabinoid System: Smart Lipids – A Novel Therapeutic Option?

Neuroplastic Effect of Exercise Through Astrocytes Activation and Cellular Crosstalk

β-elemene relieves neuropathic pain in mice through the regulation on C-X-C motif chemokine receptor 3 and GABAA receptor

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