Systemic administration of resveratrol suppress the nociceptive neuronal activity of spinal trigeminal nucleus caudalis in rats

Abstract

Although a modulatory role has been reported for the red wine polyphenol resveratrol on several types of ion channels and excitatory synaptic transmission in the nervous system, the acute effects of resveratrol in vivo, particularly on nociceptive transmission of the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous resveratrol administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from 18 SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was inhibited by resveratrol (0.5-2 mg/kg, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. These inhibitory effects were reversed after approximately 20 min. The relative magnitude of inhibition by resveratrol of SpVc WDR neuronal discharge frequency was significantly greater for noxious than non-noxious stimulation. These results suggest that, in the absence of inflammatory or neuropathic pain, acute intravenous resveratrol administration suppresses trigeminal sensory transmission, including nociception, and so resveratrol may be used as a complementary and alternative medicine therapeutic agent for the treatment of trigeminal nociceptive pain, including hyperalgesia.

Local administration of resveratrol inhibits excitability of nociceptive wide-dynamic range neurons in rat trigeminal spinal nucleus caudalis

“…These SpVc neurons responded to non-noxious and noxious mechanical stimulation and exhibited a somatic receptive field in the orofacial area (mainly the whisker pad; Fig. 1A), as described previously (Takeda et al, 2000(Takeda et al, , 2012Takehana et al, 2016). In addition, all these neurons responded to mechanical stimulation of the receptive field innervated by ophthalmic and maxillary branches.…”

“…Because previous studies have demonstrated that WDR neurons in the SpVc region have an important role in the mechanism underlying hyperalgesia and referred pain associated with orofacial pain (Takeda et al, 2000(Takeda et al, , 2005(Takeda et al, , 2012Nishikawa et al, 2004) and that the discharge of these neurons is suppressed by intravenous resveratrol administration (Takehana et al, 2016), the focus of the present study was on the effects of resveratrol on SpVc WDR neuronal activity; we did not examine nociceptive-specific neurons. Post-stimulus histograms (bin = 100 ms) were generated in response to each stimulus.…”

“…The location of the recording sites for SpVc WDR neuron activity was identified as described previously (Takeda et al 2000(Takeda et al , 2012Takehana et al, 2016). Briefly, at the end of the recording sessions, rats were deeply anesthetized and anodal direct current (DC; 30 μA, 5 min) was passed through the recording micropipette.…”

“…Extracellular recordings of SpVc WDR unit activity were performed as described previously (Takeda et al 2000(Takeda et al , 2012Takehana et al, 2016). Briefly, mechanical stimulation was used as a search stimulus to identify the receptive field quickly and to avoid sensitization of peripheral receptors.…”

“…It is well known that the spinal trigeminal nucleus caudalis (SpVc) is most important relay stations for trigeminal nociceptive inputs from inflammation and tissue injury (Sessle et al 2000;Takeda et al, 2012). Recently, Takehana et al (2016) reported that, in the absence of inflammatory or neuropathic pain, acute intravenous administration of resveratrol suppresses SpVc wide-dynamic range (WDR) neurons via both peripheral and central mechanisms. Therefore, resveratrol may be a potential CAM therapeutic agent for the treatment of trigeminal nociceptive pain without side effects.…”