Korean J Physiol Pharmacol.  2013 Apr;17(2):121-125. 10.4196/kjpp.2013.17.2.121.

Ginsenosides Have a Suppressive Effect on c-Fos Expression in Brain and Reduce Cardiovascular Responses Increased by Noxious Stimulation to the Rat Tooth

• Jung JY
• Seong KJ
• Moon IO
• Cho JH
• Kim SH
• Kim WJ

• KMID: 1429382
• DOI: http://doi.org/10.4196/kjpp.2013.17.2.121

Abstract

The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth.

Keyword

Antinociception; Cardiovascular; c-Fos; Ginsenosides; Toothache

MeSH Terms

Animals
Arterial Pressure
Brain
Ginsenosides
Heart Rate
Incisor
Naloxone
Neurons
Paraventricular Hypothalamic Nucleus
Rats
Rats, Sprague-Dawley
Solitary Nucleus
Supraoptic Nucleus
Tooth
Toothache
Ventral Thalamic Nuclei
Ginsenosides
Naloxone

Figure

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  Fig. 1 Structure of the representative ginsenosides in ginseng.

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  Fig. 2 Effects of ginsenosides on the number Fos-IR neurons increased by NS to tooth in the trigeminal spinal subnuclei and thalamus. (A) c-Fos immunoreactivity in trigeminal spinal subnuclei and thalamus. (B~D) Fos-IR neurons were increased in the trigeminal spinal subnucleus candalis (Vc) and transitional region between subnucleus interpolaris (Vi), thalamic ventral posteromedial nucleus (VPM) and centrolateral nucleus (CLN). 1.5 h after NS to the upper and lower incisor pulp with 2 M KCl. Ginsenosides reduced the number of Fos-IR neurons increased by NS to tooth in a dose-dependent manner and IC75 for ginsenosides is 50 mg/kg. Naloxon (Nal; 5 mg/kg, i.p.), an opioid antagonist, did not block the inhibitory effects of ginsenosides on the number of Fos-IR neurons increased by NS to tooth. Data represent as mean±SEM (n=5), **p<0.01.

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  Fig. 3 Effects of ginsenosides on the cardiovascular responses elevated by NS to tooth. The blood pressure (BP) and heart rate (HR) were increased immediately after NS to tooth. Ginsenosides (Gin; 50 mg/kg, i.p.) ameliorated the BP and HR increased by NS to tooth. Data represent as mean±SEM (n=12), *p<0.05.

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  Fig. 4 Effects of ginsenosides on the number of Fos-IR neurons increased by NS to tooth in the nucleus tractus solitaries (NTS) and rostral ventrolateral medulla (RVLM). (A) c-Fos immunoreactivity in NTS and RVLM. (B, C) The NS to tooth caused a robust increment of Fos-IR neurons in the NTS and RVLM, central pressor regulating areas and ginsenosides (Gin; 50 mg/kg, i.p.) reduced the number of Fos-IR neurons increased by NS to tooth in the NTS and RVLM. Data represent as mean±SEM (n=5), *p<0.05, **p<0.01.

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  Fig. 5 Effects of ginsenosides on the number of Fos-IR neurons enhanced by NS to tooth in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). (A) c-Fos immunoreactivity in PVN and SON. (B, C) Fos-IR neurons were significantly increased in the hypothalamic PVN and SON 1.5 h after NS to tooth and ginsenoside (Gin; 50 mg/kg, i.p.) reduced the number of Fos-IR neurons increased by NS to tooth. Data represent as mean±SEM (n=5), *p<0.05, **p<0.01.

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