Cannabinoid control of neurogenic inflammation

McKenna, Meagan; McDougall, Jason J.

doi:10.1111/bph.15208

Cited by 25 publications

(28 citation statements)

References 123 publications

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“…Alternatively, the expected increased availability of AEA after JZL195 might induce desensitization of the transient receptor potential vanilloid 1 channel [52], probably via the inhibition of the release of nitric oxide (NO) [53] or of neuropeptides from primary afferents at the spinal level [48]. Further, the potential effect of 2-AG or PEA on the PPARs receptors at the meningeal level could contribute to a reduction of NTG-induced inflammation [54,55].…”

Section: Discussionmentioning

confidence: 99%

Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine

Greco¹,

Demartini²,

Francavilla³

et al. 2021

Cells

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The endocannabinoid system exerts an important role in pain processing and modulation. Modulation of the system with hydrolase inhibitors of anandamide (AEA) or 2-arachidonyl glycerol (2-AG) has proved effective in reducing migraine-like features in animal models of migraine. Here, we investigated the effect of dual inhibition of the AEA and 2-AG catabolic pathways in the nitroglycerin-based animal model of migraine. The dual inhibitor JZL195 was administered to rats 2 h after nitroglycerin or vehicle injection. Rats were then exposed to the open field test and the orofacial formalin test. At the end of the tests, they were sacrificed to evaluate calcitonin gene-related peptide (CGRP) serum levels and gene expression of CGRP and cytokines in the cervical spinal cord and the trigeminal ganglion. The dual inhibitor significantly reduced the nitroglycerin-induced trigeminal hyperalgesia and pain-associated behavior, possibly via cannabinoid 1 receptors-mediated action, but it did not change the hypomotility and the anxiety behaviors induced by nitroglycerin. The decreased hyperalgesia was associated with a reduction in CGRP and cytokine gene expression levels in central and peripheral structures and reduced CGRP serum levels. These data suggest an antinociceptive synergy of the endocannabinoid action in peripheral and central sites, confirming that this system participates in reduction of cephalic pain signals.

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Section: Discussionmentioning

confidence: 99%

Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine

Greco¹,

Demartini²,

Francavilla³

et al. 2021

Cells

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“…Cannabinoids have multimodal mechanisms of action producing analgesia including: modulation of neuronal nociceptive processing, inhibition of pro-inflammatory molecule release, inhibition of mast cell activation, and modulation of endogenous opioid receptors in primary afferent pathways (Vučković et al, 2018;Amin and Ali, 2019;McKenna and McDougall, 2020). Similarly, cannabis may also provide relief for symptom clusters which accompany CNCP, such as nausea, anxiety, insomnia and depression via its effects on the endocannabinoid system (Manzanares et al, 2006;Hill et al, 2007) and so may also reduce the psychological distress associated with chronic pain (Feingold et al, 2017).…”

Section: Cannabinoids and Pain Modulationmentioning

confidence: 99%

Practical Strategies Using Medical Cannabis to Reduce Harms Associated With Long Term Opioid Use in Chronic Pain

et al. 2021

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Background: Chronic non-cancer pain (CNCP) is estimated to affect 20% of the adult population. Current United States and Canadian Chronic non-cancer pain guidelines recommend careful reassessment of the risk-benefit ratio for doses greater than 90 mg morphine equivalent dose (MED), due to low evidence for improved pain efficacy at higher morphine equivalent dose and a significant increase in morbidity and mortality. There are a number of human studies demonstrating cannabis opioid synergy. This preliminary evidence suggests a potential role of cannabis as an adjunctive therapy with or without opioids to optimize pain control.Methods: In 2017, the Canadian Opioid Guidelines Clinical Tool was created to encourage judicious opioid prescribing for CNCP patients and to reevaluate those who have been chronically using high MED. Mirroring this approach, we draw on our clinical experiences and available evidence to create a clinical tool to serve as a foundational clinical guideline for the initiation of medical cannabis in the management of CNCP patients using chronic opioid therapy.Findings: Following principles of harm reduction and risk minimization, we suggest cannabis be introduced in appropriately selected CNCP patients, using a stepwise approach, with the intent of pain management optimization. We use a structured approach to focus on low dose cannabis (namely, THC) initiation, slow titration, dose optimization and frequent monitoring.Conclusion: When low dose THC is introduced as an adjunctive therapy, we observe better pain control clinically with lower doses of opioids, improved pain related outcomes and reduced opioid related harm.

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“…Sound scientific evidence reports that the activation of the endocannabinoid system (ECS) is crucial in the inflammatory process modulation: the stimulation of cannabinoid receptors (CBrs) by agonists and inverse agonists leads to the activation of several intracellular pathways counteracting the inflammatory cascade (McKenna & McDougall, 2020; Oláh, Szekanecz, & Bíró, 2017). Although both CB1 and CB2 receptors have been detected in the immune system cells, CB2 receptors (CB2r) have a more specific pattern of expression in these cells, possessing a crucial role in cannabinoid system‐mediated regulation of inflammatory and immunity processes (Atwood & MacKie, 2010).…”

Section: Introductionmentioning

confidence: 99%

Non‐psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors‐, endocannabinoids‐, and NF‐κB‐mediated signaling

Borgonetti

Benatti

Governa

et al. 2022

Phytotherapy Research

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Cannabis sativa L. is increasingly emerging for its protective role in modulating neuroinflammation, a complex process orchestrated among others by microglia, the resident immune cells of the central nervous system. Phytocannabinoids, especially cannabidiol (CBD), terpenes, and other constituents trigger several upstream and downstream microglial intracellular pathways. Here, we investigated the molecular mechanisms of a CBD‐ and terpenes‐enriched C. sativa extract (CSE) in an in vitro model of neuroinflammation. We evaluated the effect of CSE on the inflammatory response induced by exposure to lipopolysaccharide (LPS) in BV‐2 microglial cells, compared with CBD and β‐caryophyllene (CAR), CB2 receptors (CB2r) inverse and full agonist, respectively. The LPS‐induced upregulation of the pro‐inflammatory cytokines IL‐1β, IL‐6, and TNF‐α was significantly attenuated by CSE and only partially by CBD, whereas CAR was ineffective. In BV‐2 cells, these anti‐inflammatory effects exerted by CSE phytocomplex were only partially dependent on CB2r modulation and they were mediated by the regulation of enzymes responsible for the endocannabinoids metabolism, by the inhibition of reactive oxygen species release and the modulation of JNK/p38 cascade with consequent NF‐κB p65 nuclear translocation suppression. Our data suggest that C. sativa phytocomplex and its multitarget mechanism could represent a novel therapeutic strategy for neuroinflammatory‐related diseases.

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Cannabinoid control of neurogenic inflammation

Cited by 25 publications

References 123 publications

Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine

Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine

Practical Strategies Using Medical Cannabis to Reduce Harms Associated With Long Term Opioid Use in Chronic Pain

Non‐psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors‐, endocannabinoids‐, and NF‐κB‐mediated signaling

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