Antiallodynic effect induced by [6]‐gingerol in neuropathic rats is mediated by activation of the serotoninergic system and the nitric oxide–cyclic guanosine monophosphate–adenosine triphosphate‐sensitive K⁺ channel pathway

Abstract

The present study evaluated the possible antiallodynic effect induced by [6]-gingerol in rats with L5-L6 spinal nerve ligation (SNL). Moreover, we determined the possible mechanism underlying the antiallodynic effect induced by [6]-gingerol in neuropathic rats. The animals underwent L5-L6 SNL for the purpose of developing tactile allodynia. Tactile allodynia was measured with von Frey filaments. Intrathecal administration of [6]-gingerol reversed SNL-induced tactile allodynia. The [6]-gingerolinduced antiallodynic effect was prevented by the intrathecal administration of methiothepin (30 μg per rat; nonselective 5-hydroxytryptamine [5-HT] antagonist), WAY-100635 (6 μg per rat; selective 5-HT 1A receptor antagonist), SB-224289 (5 μg per rat; selective 5-HT 1B receptor antagonist), BRL-15572 (4 μg per rat; selective 5-HT 1D receptor antagonist), and SB-659551 (6 μg per rat; selective 5-HT 5A receptor antagonist), but naloxone (50 μg per rat; nonselective opioid receptor antagonist) did not prevent the [6]-gingerol-induced antiallodynic effect. Moreover, intrathecal administration of Nω-nitro-L-arginine methyl ester (100 μg per rat; nonselective nitric oxide [NO] synthase inhibitor), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μg per rat; inhibitor of guanylate cyclase), and glibenclamide (50 μg per rat; channel blocker of adenosine triphosphate [ATP]-sensitive K + channels) prevented the [6]-gingerol-induced antiallodynic effect. These data suggest that the antiallodynic effect induced by [6]-gingerol is mediated by the serotoninergic system involving the activation of 5-HT 1A/1B/1D/5A receptors, as well as the NO-cyclic guanosine monophosphate-ATP-sensitive K + channel pathway but not by the opioidergic system.

Anti-allodynic effect induced by curcumin in neuropathic rat is mediated through the NO-cyclic-GMP-ATP sensitive K+ channels pathway

“…All experiments were performed on female Wistar rats weighing 140-160 g (n = 162). Previous studies have demonstrated no difference in tactile allodynia between female and male rats in the SNL model [23,28,29]. For this reason, we decided to use female rat in this study.…”

“…Other studies have reported that drugs which activate the NO-cGMP pathway seem to modulate the opening of the K + channels in order to produce nociception [20]. Previous studies have indicated that natural products produce anti-nociceptive and anti-allodynic effects through the NO-cGMP-ATP sensitive channels K + pathway [20][21][22][23][24][25][26]. There is evidence that suggests that curcumin exhibits its anti-nociceptive effect by directly stimulating K + ATP channels in an inflammatory pain model [27].…”

Ginger (Zingiber officinale Roscoe) as a nutraceutical: Focus on the metabolic, analgesic, and antiinflammatory effects

“…Moreover, 6-gingerol attenuated acetic acid-induced writhing response and formalin-induced pain (Young et al, 2005). Preclinical studies subsequently provided evidence for the therapeutic effect of 6-gingerol in rats with L5-L6 spinal nerve ligation (Mata-Bermudez, Izquierdo, de los Monteros-Zuñiga, Coen, & Godínez-Chaparro, 2018).…”

“…The antiallodynic effect induced by intrathecal administration of 6-gingerol was mediated, at least in part, by the NO-cGMP-ATPsensitive K+ channel pathways and by the serotoninergic system via activation of 5-HT A/1B/1D/1F (Mata-Bermudez et al, 2018).…”

“…Moreover, 6‐gingerol attenuated acetic acid–induced writhing response and formalin‐induced pain (Young et al, 2005). Preclinical studies subsequently provided evidence for the therapeutic effect of 6‐gingerol in rats with L5–L6 spinal nerve ligation (Mata‐Bermudez, Izquierdo, de los Monteros‐Zuñiga, Coen, & Godínez‐Chaparro, 2018). The antiallodynic effect induced by intrathecal administration of 6‐gingerol was mediated, at least in part, by the NO–cGMP–ATP‐sensitive K+ channel pathways and by the serotoninergic system via activation of 5‐HT A/1B/1D/1F (Mata‐Bermudez et al, 2018).…”