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Fig. 4 | The Journal of Headache and Pain

Fig. 4

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

Fig. 4

Dual MAGL/FAAH inhibitor AKU-005 reduces nociceptive firing mediated by CB1 receptors. A Example traces of APs recorded from the peripheral part of trigeminal nerve innervating rat meninges for the control condition before any application (top), during the 1-min active phase of KCl-induced spiking activity without (middle) and in the presence of AKU-005 (100 nM) (bottom trace). B Time courses of spike frequency (10-s bin size) induced by two subsequent 10-min pulses of 50 mM KCl and 1 ΌM Capsaicin, in the presence of only 100 nM AKU-005 and the combination of 100 nM AKU-005 and 1 ΌM AM-251 during the 2nd KCl pulse. After exposure to AKU-005, the 2nd KCl-induced firing was reduced. To test that the effect was mediated by cannabinoid CB1 receptors, the experiment was repeated in the presence of specific CB1 blocker AM-251 (1 µM). C Firing induced during the 2nd KCl pulse was reduced in the presence of AKU-005 (AKU) application (N = 7, Kruskal Wallis test, * = 0.03) in comparison to the control (N = 8) condition (Cntr) (the ratio of the APs between 2nd and 1st KCL pulse). Firing was increased again by the combination of both AM-251 and AKU-005 (N = 7, Kruskal Wallis test, ** = 0.004). D Blockade of CB1 receptors did not change the efficacy of next applied capsaicin compared to application of only AKU-005 (number of APs/1 min)

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