Inhibiting Endocannabinoid Hydrolysis as Emerging Analgesic Strategy Targeting a Spectrum of Ion Channels Implicated in Migraine Pain - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35457225/
Migraine is a disabling neurovascular disorder characterized by severe pain with still limited efficient treatments. Endocannabinoids, the endogenous painkillers, emerged, alternative to plant cannabis, as promising analgesics against migraine pain. In this thematic review, we discuss how inhibition of the main endocannabinoid-degrading enzymes, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), could raise the level of endocannabinoids (endoCBs) such as 2-AG and anandamide in order to alleviate migraine pain.
Conclusion/Relevance: The specific distribution and homeostasis of endoCBs in the main regions of the nociceptive system and their generation 'on demand', along with recent availability of MAGL and FAAH inhibitors suggest new perspectives for endoCBs-mediated analgesia in migraine pain.
• Source: International Journal of Molecular Sciences
• Conclusion: “The specific distribution and homeostasis of endoCBs [endocannabinoids] in the main regions of the nociceptive system and their generation ‘on demand’, along with recent availability of MAGL [monoacylglycerol lipase] and FAAH [fatty acid amide hydrolase] inhibitors suggest new perspectives for endoCBs-mediated analgesia in migraine pain.”
• Endocannabinoids are endogenous painkillers—unlike cannabis. The inhibition of the main endocannabinoid-degrading enzymes, MAGL and FAAH, could increase the concentrations of endocannabinoids (endoCBs) including 2-AG and anandamide to relieve migraine pain.
• The effect of this therapy is due to the specificity and selectivity of the experimental compounds. These compounds need to target sites where endoCB can be mobilized with regard to local neuroimmune activity.
• The authors wrote, “This field of research needs further investigation, which now become possible by combining various modern methods including highly sensitive ABPP assays to evaluate activities and the sensitivity to inhibition of endoCBs hydrolases, LC/MS spectrometry to determine endoCB levels in specific tissues, along with electrophysiological tools and behavioral testing in animals. Identification of novel treatments acting specifically on druggable molecular targets in the brain and in the peripheral meningeal trigeminovascular nociceptive system suggests a promising approach to control migraine pain, ultimately limiting the undesired side effects of new treatments.”