The monoacylglycerol lipase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model
Open accessAbstract
Aim The present study tested whether the selective monoacylglycerol lipase (MAGL) inhibitor JZL184 would reduce allodynia and paw edema in the carrageenan test.Main methods The anti-edematous and anti-allodynic effects of JZL184 were compared to those of PF-3845, an inhibitor of fatty acid amide hydrolase (FAAH), and diclofenac, a non-selective cyclooxygenase inhibitor. Cannabinoid receptor involvement in the anti-edematous and anti-allodynic effects of JZL184 was evaluated by administration of the respective CB1 and CB2 receptor antagonists rimonabant and SR144528 as well as with CB1(-/-) and CB2(-/-) mice. JZL184 (1.6, 4, 16, or 40mg/kg) was administered for six days to assess tolerance.Key findings JZL184 administered before or after carrageenan significantly attenuated carrageenan-induced paw edema and mechanical allodynia. Complementary genetic and pharmacological approaches revealed that the anti-allodynic effects of JZL184 required both CB1 and CB2 receptors, but only CB2 receptors mediated its anti-edematous actions. Importantly, both the anti-edematous and anti-allodynic effects underwent tolerance following repeated injections of high dose JZL184 (16 or 40mg/kg), but repeated administration of low dose JZL184 (4mg/kg) retained efficacy.Significance These results suggest that the MAGL inhibitor JZL184 reduces inflammatory nociception through the activation of both CB1 and CB2 receptors, with no evidence of tolerance following repeated administration of low doses.
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Pharmacological inhibition or genetic deletion of FAAH attenuates carrageenan-induced inflammation as well as mechanical allodynia and thermal hyperalgesia.
“For example, pharmacological inhibition or genetic deletion of FAAH attenuates carrageenan-induced inflammation as well as mechanical allodynia and thermal hyperalgesia (increased sensitivity to a noxious heat stimuli) (Ghosh et al, 2013;Karbarz et al, 2009;Lichtman et al, 2004).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Ghosh et al, 2013
Inhibition of MAGL attenuates carrageenan-induced acute paw edema and inflammatory pain.
“Similarly, inhibition of MAGL, the primary catabolic enzyme of 2-AG (Blankman et al, 2007), attenuates carrageenan-induced, acute paw edema and inflammatory pain (Comelli et al, 2007;Ghosh et al, 2013;Ignatowska-Jankowska et al, 2014).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Ghosh et al, 2013
The selective MAGL inhibitors JZL184 and KML129 attenuate carrageenan-induced mechanical allodynia through CB1 and CB2 receptor-dependent mechanisms, but only CB2 receptors mediate the anti-edematous effects of these inhibitors.
“The selective MAGL inhibitors JZL184 and KML129 attenuate carrageenan-induced mechanical allodynia through CB 1 and CB 2 receptor-dependent mechanisms, but only CB 2 receptors mediate the antiedematous effects of these inhibitors (Ghosh et al, 2013;Ignatowska-Jankowska et al, 2014).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Ghosh et al, 2013
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- Authors
- Ghosh, S., Wise, L. E., Chen, Y., Gujjar, R., Mahadevan, A., Cravatt, B. F., & Lichtman, A. H.
- Affiliations
- Virginia Commonwealth University (US)
- Organix (United States) (US)
- Scripps Research Institute (US)
- Corresponding author
- Lichtman, Aron H.
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 92
- Issue
- 8-9
- Pages
- 498-505
- ISSN
- 0024-3205 (ISSN-L)
- PMC
- PMC3717616
- OpenAlex
- W2005449195
- Cited by
- 127
- References
- 60
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 9 · 2020: 6 · 2019: 3 · 2018: 17 · 2017: 9 · 2016: 9 · 2015: 11 · 2014: 18 · 2013: 12 · 2012: 1
- FWCI
- 9.88
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (P01DA009789, P01DA017259, R01DA003672, R01DA005488, R01-DA-03672, P50DA005274)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- JZL184, monoacylglycerol lipase inhibitors, inflammatory pain, carrageenan-induced paw edema, mechanical allodynia, CB1 receptor, CB2 receptor, diclofenac, rimonabant, SR144528, drug tolerance, endocannabinoid system
- MeSH terms
- Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Anti-Inflammatory Agents, Non-Steroidal, Carrageenan, Diclofenac, Edema, Hyperalgesia, Inflammation, Mice, Inbred C57BL, Monoacylglycerol Lipases, Pain, Pain Measurement, Physical Stimulation, Piperidines, Pyridines, Mice, Knockout, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Mice, Benzodioxoles
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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