Effects of Centrally Administered Endocannabinoids and Opioids on Orofacial Pain Perception in Rats.

BACKGROUND AND PURPOSE:

Endocannabinoids and opioids play a vital role in mediating pain-induced analgesia. The specific effects of these compounds within orofacial region are largely unknown. In this study we tried to determine whether the increase of cannabinoid and opioid concentration in cerebrospinal fluid affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles.

EXPERIMENTAL APPROACH:

The study objectives were realized on rats using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation. The amplitude of ETJ was the 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) produced a reduction of ETJ amplitude. The antinociceptive effect of AEA, EM-2, URB597 and JZL195 was blocked by CB1R antagonist, AM251 and by MOR-antagonist, β-funaltrexamine (β-FNA). In contrast to AEA, 2-arachidonoylglycerol (2-AG) 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 MOR 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.

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