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Fig. 8 | The Journal of Headache and Pain

Fig. 8

From: Potent dual MAGL/FAAH inhibitor AKU-005 engages endocannabinoids to diminish meningeal nociception implicated in migraine pain

Fig. 8

AKU-005 and AEA promote paired-pulse depression in meningeal afferents. A Time courses of spike frequency (10-s bin size) induced by APs recorded from the peripheral part of trigeminal nerve innervating rat meninges within the 1-min active phase of the 2nd KCl pulse. By clustering the recordings, we defined paired-pulse potentiation (PPP) when the number KCl-evoked APs was higher during the 2nd KCl pulse and paired-pulse depression (PPD) when the number KCl-evoked APs was higher during the 1st KCl pulse. B AP morphologies corresponding to PPP and PPD recordings showed no differences. C A statistical analysis showed that physiologically PPP are more frequent than PPD. In the presence of AKU-005 or AEA during the 2nd KCl pulse, PPD clusters are more prevalent for AKU-005 and AEA, while PPP clusters are less prevalent under the same treatments. PPP and PPD clusters are comparable when 2-AG was applied during the 2nd KCl pulse

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