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Br J Pharmacol. 2017 Nov;174(21):3780-3789. doi: 10.1111/bph.13970. Epub 2017 Aug 30.

Effects of centrally administered endocannabinoids and opioids on orofacial pain perception in rats.

Author information

1
Department of Cardiovascular and Thoracic Surgery, University of Ulm, Ulm, Germany.
2
Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
3
Department of Cardiac Anesthesiology, University Hospital Ulm, Ulm, Germany.
4
Department of Cardiovascular Physiology, Interdepartmental Chair of Experimental and Clinical Physiology, Medical University of Lodz, Lodz, Poland.

Abstract

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 CB1 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 CB1 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.

PMID:
28771697
PMCID:
PMC5647185
DOI:
10.1111/bph.13970
[Indexed for MEDLINE]
Free PMC Article

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