Background: Recent studies pointed up that curcumin produces an anti-nociceptive effect in inflammatory and neuropathic pain. However, the possible mechanisms of action that underline the anti-allodynic effect induced by curcumin are not yet established. The purpose of this study was to determine the possible anti-allodynic effect of curcumin in rats with L5-L6 spinal nerve ligation (SNL). Furthermore, we study the possible participation of the NOcyclic GMP-ATP-sensitive K + channels pathway in the anti-allodynic effect induced by curcumin. Methods: Tactile allodynia was measured using von Frey filaments by the up-down method in female Wistar rats subjected to SNL model of neuropathic pain. Results: Intrathecal and oral administration of curcumin prevented, in a dose-dependent fashion, SNL-induced tactile allodynia. The anti-allodynic effect induced by curcumin was prevented by the intrathecal administration of L-NAME (100 μg/rat, a non-selective nitric oxide synthase inhibitor), ODQ (10 μg/rat, an inhibitor of guanylatecyclase), and glibenclamide (50 μg/rat, channel blocker of ATP-sensitive K + channels). Conclusions: These data suggest that the anti-allodynic effect induced by curcumin is mediated, at least in part, by the NO-cyclic GMP-ATP-sensitive K + channels pathway in the SNL model of neuropathic pain in rats.

The design, stereoselective synthesis and in vivo antiallodynic activity of four novel paroxetine analogs, named 3‐hydroxy paroxetines (3HPXs), is reported herein. Among the novel synthesized compounds, three showed an antiallodynic effect, while (R,R)‐3HPX was found to be 2.5 times more bioactive than (‐)‐paroxetine itself in neuropathic rats. Consequently, the current investigation not only discloses a novel promising analgesic drug, but also reveals that functionalization at the C3 position of paroxetine could be as effective as the common functionalization at either C4 or within the sesamol group.