Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice

Nozaki, Chihiro; Markert, Astrid; Zimmer, Andreas

doi:10.1016/j.euroneuro.2015.04.001

Cited by 35 publications

(48 citation statements)

References 29 publications

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“…Similarly, mice lacking the 2-AG-catabolising enzyme monoacylglycerol lipase (MAGL) exhibited significantly augmented nociceptive behaviour in the formalin and acetic acid tests and no alterations in thermal tail-withdrawal latency, effects that were likely due to desensitisation of CB1R (Petrenko, Yamazaki, Sakimura, Kano, & Baba, 2014;Schlosburg et al, 2010). In a recent study, nitroglycerin-induced mechanical allodynia and neuronal activation of the trigeminal nucleus to model migraine were abolished in FAAH-deficient mice, results also seen in mice administered FAAH inhibitors (Nozaki, Markert, & Zimmer, 2015). These effects were shown to be CB1Rmediated and they infer that one or more FAAH substrates mediate antinociception via CB1R.…”

Section: Near Here]mentioning

confidence: 92%

Cannabinoids and Pain: Sites and Mechanisms of Action

Starowicz

Finn

2017

Advances in Pharmacology

134

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The endocannabinoid system, consisting of the cannabinoid receptor (CBR) and cannabinoid receptor (CBR), endogenous cannabinoid ligands (endocannabinoids), and metabolizing enzymes, is present throughout the pain pathways. Endocannabinoids, phytocannabinoids, and synthetic cannabinoid receptor agonists have antinociceptive effects in animal models of acute, inflammatory, and neuropathic pain. CBR and CBR located at peripheral, spinal, or supraspinal sites are important targets mediating these antinociceptive effects. The mechanisms underlying the analgesic effects of cannabinoids likely include inhibition of presynaptic neurotransmitter and neuropeptide release, modulation of postsynaptic neuronal excitability, activation of the descending inhibitory pain pathway, and reductions in neuroinflammatory signaling. Strategies to dissociate the psychoactive effects of cannabinoids from their analgesic effects have focused on peripherally restricted CBR agonists, CBR agonists, inhibitors of endocannabinoid catabolism or uptake, and modulation of other non-CBR/non-CBR targets of cannabinoids including TRPV1, GPR55, and PPARs. The large body of preclinical evidence in support of cannabinoids as potential analgesic agents is supported by clinical studies demonstrating their efficacy across a variety of pain disorders.

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Section: Near Here]mentioning

confidence: 92%

Cannabinoids and Pain: Sites and Mechanisms of Action

Starowicz

Finn

2017

Advances in Pharmacology

134

View full text Add to dashboard Cite

show abstract

“…FAAH inhibitors (ie, PF-3845 and URB597) reverse allodynia in a mouse model of nitroglycerin-induced migraine through a CB 1 receptor-dependent mechanism (Nozaki et al, 2015). Others have found that the peripherally restricted FAAH inhibitor URB937 administration evoked anti-hyperalgesic effect in rats (Greco et al, 2015).…”

Section: Models Of Migraine Headachementioning

confidence: 99%

The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain

Donvito

Nass

Wilkerson

et al. 2017

Neuropsychopharmacol.

222

168

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A great need exists for the development of new medications to treat pain resulting from various disease states and types of injury. Given that the endogenous cannabinoid (that is, endocannabinoid) system modulates neuronal and immune cell function, both of which play key roles in pain, therapeutics targeting this system hold promise as novel analgesics. Potential therapeutic targets include the cannabinoid receptors, type 1 and 2, as well as biosynthetic and catabolic enzymes of the endocannabinoids N-arachidonoylethanolamine and 2-arachidonoylglycerol. Notably, cannabinoid receptor agonists as well as inhibitors of endocannabinoid-regulating enzymes fatty acid amide hydrolase and monoacylglycerol lipase produce reliable antinociceptive effects, and offer opioid-sparing antinociceptive effects in myriad preclinical inflammatory and neuropathic pain models. Emerging clinical studies show that 'medicinal' cannabis or cannabinoid-based medications relieve pain in human diseases such as cancer, multiple sclerosis, and fibromyalgia. However, clinical data have yet to demonstrate the analgesic efficacy of inhibitors of endocannabinoid-regulating enzymes. Likewise, the question of whether pharmacotherapies aimed at the endocannabinoid system promote opioid-sparing effects in the treatment of pain reflects an important area of research. Here we examine the preclinical and clinical evidence of various endocannabinoid system targets as potential therapeutic strategies for inflammatory and neuropathic pain conditions.

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“…Increased expression of CB2 but not CB1 receptors was observed in tongue epithelial cells in patients with burning mouth syndrome [246]. In migraine patients, AEA and 2-AG were observed to be downregulated, and FAAH was upregulated [247,248]. In a nitroglycerin-induced migraine pain model in rats, FAAH activity was increased in the medulla and hypothalamus, and the activity of both FAAH and MAGL was increased in the mesencephalon [249].…”

Section: Modulation Of Cannabinoid Receptors and Endocannabinoids In mentioning

confidence: 99%

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

Hossain

Ando

Unno

2020

IJMS

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Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in the brain. Alternative approaches have been developed to overcome this problem by selectively targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoids that may be locally synthesized on demand at sites where their actions are pertinent. Many preclinical studies have reported that these strategies are effective for treating neuropathic pain and produce no or minimal side effects. Recently, we observed that inhibition of degradation of a major endocannabinoid, 2-arachydonoylglycerol, can attenuate NOP following trigeminal nerve injury in mice. This review will discuss the above-mentioned alternative approaches that show potential for treating neuropathic pain including NOP.

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Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice

Cited by 35 publications

References 29 publications

Cannabinoids and Pain: Sites and Mechanisms of Action

Cannabinoids and Pain: Sites and Mechanisms of Action

The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

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