CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages

Han, Ki Hoon; Lim, Sunny; Ryu, Jewon; Lee, Cheol-Whan; Kim, Yuna; Kang, Ju‐Hee; Kang, Suk-Yun; Ahn, Yeong Ki; Park, Chan-Sik; Kim, Jae Joong

doi:10.1093/cvr/cvp240

Cited by 201 publications

(191 citation statements)

References 27 publications

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“…However, inflamed tissue has been shown to express 10-100 times the number of CB2 receptors compared to CB1 receptor mRNA, suggesting that EDN may act primarily through CB2 receptors [176,177]. CB2 receptor mRNA is found primarily on immune cells, to include mast cells, T lymphocytes, leukocytes, natural killer cells and macrophages [176,177].…”

Section: The Role Of the Endocannabinoid System In Dry Needling-mediamentioning

confidence: 99%

Peripheral and Spinal Mechanisms of Pain and Dry Needling Mediated Analgesia: A Clinical Resource Guide for Health Care Professionals

Butts¹,

Dunning²

2016

Int J Phys Med Rehabil

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There are a number of biochemical, biomechanical, endocrinological and neurovascular mechanisms underpinning the anti-nociceptive and anti-inflammatory effects of dry needling (DN). While myofascial trigger points likely play a role in peripheral pain, a diagnostic tool for localizing them has not been validated, and DN studies that have targeted trigger points to elicit localized twitch responses have reported mixed results. Therefore, the mechanism responsible for DN-mediated analgesia may be more complicated. DN activates opioid-based pain reduction, mediated by endogenous cannabinoids and the sympathetic nervous system, and non-opioid pain relief via serotonin and norepinephrine from the brain stem. DN also triggers the hypothalamic-pituitary-adrenal axis centrally and the corticotropin releasing hormone-proopiomelanocortin-corticosteroid axis locally to inhibit cox-2, reducing inflammatory cytokines. Recent studies demonstrate that DN combined with mechanical and/or electrical stimulation may reverse PKC-mediated peripheral hyperalgesic priming by normalizing nociceptive channels, to include TRPV, ASIC, TTX and P2X/Y. Electrical DN (EDN) stimulates immune cells, fibroblasts and keratinocytes to release CGRP and substance-P, altering the stimulation of TTX receptors to reverse hyperalgesia. It also encourages the supraoptic nucleus to release oxytocin to quiet ASIC receptors peripherally and stimulate opioid interneurons spinally. Moreover, EDN inhibits ERK1/2 kinase pathways of inflammation in the spinal cord and stimulates Aδ fibers and N/OFQ to reverse C-fiber mediated central changes. Mechanotransduction of fibroblasts and peripheral nerves via TRPV1 and P2X/Y-mediated intracellular Ca 2+ wave propagation and subsequent activation of the nucleus accumbens inhibits spinal pain transmission via glycinergic and opioidergic interneurons. The increased ATP is metabolized to adenosine, which activates P1 purinergic receptors, events considered key to DN analgesia and rho kinase-based tissue remodeling. Mechanotransduction-mediated release of histamine further explains analgesia secondary to needling points distal to pain. DN-mediated analgesia is dependent on a number of synergistic physiologic events involving biochemical and mechanical processes in neural, connective and muscle tissue.

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Section: The Role Of the Endocannabinoid System In Dry Needling-mediamentioning

confidence: 99%

Peripheral and Spinal Mechanisms of Pain and Dry Needling Mediated Analgesia: A Clinical Resource Guide for Health Care Professionals

Butts¹,

Dunning²

2016

Int J Phys Med Rehabil

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“…Han et al 24 examined the relative expression of CB1 and CB2 receptors in freshly isolated human monocytes and identified significant upregulation of CB1 receptors as monocytes differentiate into macrophages. This upregulation of CB1 receptor expression correlated with the increase in reactive oxygen species (ROS) production.…”

Section: Cannabinoids and Atherosclerosis Effect On Immune Cellsmentioning

confidence: 99%

Cannabinoids and Atherosclerotic Coronary Heart Disease

Singla

Sachdeva

Mehta

2012

Clinical Cardiology

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Marijuana is the most abused recreational drug in the United States. Cannabinoids, the active ingredients of marijuana, affect multiple organ systems in the human body. The pharmacologic effects of marijuana, based on stimulation of cannabinoid receptors CB1 and CB2, which are widely distributed in the cardiovascular system, have been well described. Activation of these receptors modulates the function of various cellular elements of the vessel wall, and may contribute to the pathogenesis of atherosclerosis. Clinically, there are reports linking marijuana smoking to the precipitation of angina and acute coronary syndromes. Recently, large published clinical trials with CB1 antagonist rimonabant did not show any significant benefit of this agent in preventing progression of atherosclerosis. In light of these findings and emerging data on multiple pathways linking cannabinoids to atherosclerosis, we discuss the literature on the role of cannabinoids in the pathophysiology of atherosclerosis. We also propose a marijuana paradox, which implies that inhalation of marijuana may be linked to precipitation of acute coronary syndromes, but modulation of the endocannabinoid system by a noninhalation route may have a salutary effect on the development of atherosclerosis.The authors have no funding, financial relationships, or conflicts of interest to disclose.

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“…In addition, ∆‐9‐THC‐stimulated human T‐cells show less proliferation and inhibition of interferon‐gamma production, as well as downregulation of T‐helper 1 cells78 that are present in atherosclerotic lesions and which contribute to the inflammatory state of the lesions. The endocannabinoid system (ECS) and cannabinoid receptors (both CB1 and CB2) are highly active in cells found in atherosclerotic plaques such as macrophages and vascular smooth muscle cells 2, 79. Macrophages are activated by oxidized LDL through increased (anandamide) and 2‐arachidonoylglycerol (2‐AG) concentration, as well as upregulation of CB1 and CB2, thus initiating cholesterol accumulation in immune cells, affecting endothelial cells, and vascular smooth muscle cells 2, 79, 80…”

Section: The Ecs In Cvd Pathologymentioning

confidence: 99%

Cannabinoids, the Heart of the Matter

Alfulaij

Meiners

Michalek

et al. 2018

JAHA

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CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages

Abstract: CB1 promotes pro-inflammatory responses of macrophages through ROS production, which is negatively regulated by CB2 through Rap1 activation. Blocking CB1 together with selective activation of CB2 may suppress pro-inflammatory responses of macrophages.

Cited by 201 publications

References 27 publications

Peripheral and Spinal Mechanisms of Pain and Dry Needling Mediated Analgesia: A Clinical Resource Guide for Health Care Professionals

Peripheral and Spinal Mechanisms of Pain and Dry Needling Mediated Analgesia: A Clinical Resource Guide for Health Care Professionals

Cannabinoids and Atherosclerotic Coronary Heart Disease

Cannabinoids, the Heart of the Matter

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