TY - JOUR T1 - Curcumin Acts as a Positive Allosteric Modulator of <em>α</em><sub>7</sub>-Nicotinic Acetylcholine Receptors and Reverses Nociception in Mouse Models of Inflammatory Pain JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 190 LP - 200 DO - 10.1124/jpet.117.245068 VL - 365 IS - 1 AU - Eslam Gaber El Nebrisi AU - Deniz Bagdas AU - Wisam Toma AU - Halima Al Samri AU - Anna Brodzik AU - Yasmin Alkhlaif AU - Keun-Hang Susan Yang AU - Frank Christopher Howarth AU - Imad M. Damaj AU - Murat Oz Y1 - 2018/04/01 UR - http://jpet.aspetjournals.org/content/365/1/190.abstract N2 - Effects of curcumin, a major ingredient of turmeric, were tested on the function of the α7-subunit of the human nicotinic acetylcholine (α7-nACh) receptor expressed in Xenopus oocytes and on nociception in mouse models of tonic and visceral pain. Curcumin caused a significant potentiation of currents induced by acetylcholine (ACh; 100 μM) with an EC50 value of 0.2 µM. The effect of curcumin was not dependent on the activation of G-proteins and protein kinases and did not involve Ca2+-dependent Cl− channels expressed endogenously in oocytes. Importantly, the extent of curcumin potentiation was enhanced significantly by decreasing ACh concentrations. Curcumin did not alter specific binding of [125I]α-bungarotoxin. In addition, curcumin attenuated nociceptive behavior in both tonic and visceral pain models without affecting motor and locomotor activity and without producing tolerance. Pharmacological and genetic approaches revealed that the antinociceptive effect of curcumin was mediated by α7-nACh receptors. Curcumin potentiated the antinociceptive effects of the α7-nACh receptor agonist N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU282987). Collectively, our results indicate that curcumin is a positive allosteric modulator of α7-nACh receptor and reverses nociception in mouse models of tonic and visceral pain. ER -