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Effects of centrally administered endocannabinoids and opioids on orofacial pain perception in rats
Author(s) -
Zubrzycki Marek,
Janecka Anna,
Liebold Andreas,
Ziegler Mechthild,
Zubrzycka Maria
Publication year - 2017
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13970
Subject(s) - am251 , endocannabinoid system , fatty acid amide hydrolase , monoacylglycerol lipase , pharmacology , cannabinoid , anandamide , cannabinoid receptor , chemistry , 2 arachidonoylglycerol , depolarization induced suppression of inhibition , periaqueductal gray , neuroscience , medicine , antagonist , receptor , central nervous system , psychology , biochemistry , midbrain
Background and Purpose Endocannabinoids and opioids play a vital role in mediating pain‐induced analgesia. The specific effects of these compounds within the orofacial region are largely unknown. In this study, we tried to determine whether an increase in cannabinoid and opioid concentration in the CSF affects impulse transmission between the motor centres localized in the vicinity of the third and fourth cerebral ventricles. Experimental Approach The study objectives were realized on rats using a method that allows the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation. The amplitude of ETJ was a measure of the effect of neurotransmitters on neural structures. Key Results Perfusion of cerebral ventricles with anandamide (AEA), endomorphin‐2 (EM‐2), URB597, an inhibitor of fatty acid amide hydrolase (FAAH) and JZL195, a dual inhibitor of FAAH and monoacylglycerol lipase (MAGL) reduced the ETJ amplitude. The antinociceptive effect of AEA, EM‐2, URB597 and JZL195 was blocked by CB 1 receptor antagonist, AM251 and by μ receptor‐antagonist, β‐funaltrexamine. In contrast to AEA, 2‐arachidonoylglycerol alone did not decrease ETJ amplitude. Conclusions and Implications We demonstrated that in the orofacial area, analgesic activity is modulated by AEA and that EM‐2‐induced antinociception was mediated by μ and CB 1 receptors. The action of AEA and EM‐2 is tightly regulated by FAAH and FAAH/MAGL, by preventing the breakdown of endogenous cannabinoids in regions where they are produced on demand. Therefore, the current findings support the therapeutic potential of FAAH and FAAH/MAGL inhibitors as novel pharmacotherapeutic agents for orofacial pain.