Abstract

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.