Influence of serotonin receptor antagonists on substance P and serotonin release evoked by tooth pulp stimulation with electro-acupuncture in the trigeminal nucleus cudalis of the rabbit

doi:10.1016/S0168-0102(01)00207-3

Neuroscience Research

Volume 40, Issue 1, May 2001, Pages 45-51

https://doi.org/10.1016/S0168-0102(01)00207-3 Get rights and content

Abstract

We studied the effect of NAN-190 (5-HT_1A antagonist), ketanserin (5-HT₂ antagonist) and ICS 205-930 (5-HT₃ antagonist) on tooth pulp stimulation (TPS)-induced 5-HT release and substance P (SP) release in the superficial layers of the trigeminal nucleus caudalis (SpVc-I,II) in the presence or absence of electro-acupuncture (EAP). TPS slightly increased 5-HT release and significantly increased SP release. In combination with EAP, TPS-induced 5-HT release was remarkably enhanced, whereas SP release was significantly suppressed. Pretreatment with NAN-190 (3.5 mg/kg, i.v.) significantly enhanced the increase in TPS-induced 5-HT release in the presence of EAP. On the other hand, the increase of 5-HT release induced following TPS in the presence of EAP was inhibited by pretreatment with ketanserin (2.5 mg/kg, i.v.) and ICS 205-930 (1 mg/kg, i.v.). When NAN-190 was pre-treated in the animals combined TPS and EAP, the amount of SP release was significantly reduced compared with the absence of this drug. On the other hand, pretreatment with ketanserin and ICS 205-930 reversed the inhibitory effect of EAP on the TPS-generated SP release, especially ICS 205-930, which remarkably enhanced TPS-induced SP release compared with the absence of this drug. On the basis of the obtained results, we concluded that NAN-190 and ICS 205-930 act on EAP-induced analgesia positively and suppressively, respectively, by regulation of TPS-generated SP release through activation of their subtype receptors. On the other hand, ketanserin does not affect TPS-induced 5-HT release and SP release in the presence of EAP.

Introduction

Although acupuncture has been a very common healing technique in the treatment of pain in the oriental world since ancient age, its detailed mechanism still remains unresolved. The spinal trigeminal nucleus (STN) is considered to be closely associated with the perception and transmission of orofacial sensory information (Kelly, 1981). STN is divided into three subnuclei: oralis, interpolaris and caudalis (Olszewki, 1950). Among these subnuclei, subnucleus caudalis is thought to be most functionally and anatomically analogous to spinal dorsal horn (Hu et al., 1981) and a site for the relay nucleus of the craniofacial nociceptive information to higher levels of the brain. We have already demonstrated that electro-acupuncture (EAP) produced inhibition of tooth pulp stimulation (TPS)-evoked potential and substance P (SP) release in the superficial layers of the trigeminal nucleus caudalis (SpVc-I,II) through activation of the descending 5-HTergic systems linking up with opioidergic systems (Takagi et al., 1996). With regard to 5-HT receptor subtypes, in the last decade, at least seven distinct 5-HT receptor subtypes have been identified. Therefore, we previously investigated which subtypes are involved in the modulation of EAP using electrophysiological technique. As a result, we obtained the evidence that some antagonists of 5-HT receptor subtypes enhanced the inhibitory action of EAP against field potentials evoked by TPS, whereas others suppressively acted on EAP-induced analgesia, thus suggesting that multiple 5-HT receptor subtypes involved in modulation of EAP may be grouped into two types (Takagi and Yonehara, 1998). In the present study, in order to elucidate what mechanisms are involved in the manifestation of two types of phenomena through 5-HTergic pathway, we examined the effect of antagonists of 5-HT receptor subtypes divided into two groups on TPS-evoked 5-HT release and SP release in the presence of EAP in SpVc-I,II.

Section snippets

Perfusion of the S_pVc-I,II

A total of at least 110 male rabbits (approx. 2.5–3.0 kg b.w.) were used in this study. The animals were anesthetized with urethane (1.0 g/kg i.p.). A bipolar, enamel-insulated stimulating electrode (0.1 mm diameter, 0.5 mm exposed tip) was inserted into the pulp and fixed with dental cement and resin. The animal was then placed in a stereotaxic apparatus and a push–pull cannula was introduced into the superficial layers of the trigeminal nucleus on the ipsilateral side to the stimulating

Effect of EPA on TPS-induced 5-HT release in the S_pVc,I-II

As shown in Fig. 1, the amount of 5-HT in the perfusate was initially high, but gradually decreased with time to a steady level (corresponding to fraction Nos. 4 and 5) 2–3 h after starting perfusion (Fig. 1) and this level was maintained for at least 6 h (fraction No. 14). The level of 5-HT in the resting state, that is, in two 20-min fractions obtained in a 40-min period, from 140 min after starting the perfusion to 180 min (fraction No. 4 and 5), was 79.6±10.2 pg/20 min (one fraction, n=8).

Discussion

A number of studies on pain in recent years have suggested that two modulatory systems are controlling conduction of the ascending sensory message at the level related to the first synaptic relay stations in the trigeminal nuclei and spinal cord (Duggan, 1978, Fields and Basbaum, 1978, Besson and Chaouch, 1987). One is the intrinsic mechanism associated with the segmental opioid system and the other is a descending monoaminergic system originating in the brainstem. We have already reported that

Acknowledgements

I would like to thank Dr Jun Takagi for his help with excellent technique. This study was supported by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Science/Sports and Culture of Japan (07672013).

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Influence of serotonin receptor antagonists on substance P and serotonin release evoked by tooth pulp stimulation with electro-acupuncture in the trigeminal nucleus cudalis of the rabbit

Abstract

Introduction

Section snippets

Perfusion of the SpVc-I,II

Effect of EPA on TPS-induced 5-HT release in the SpVc,I-II

Discussion

Acknowledgements

Pain

Neuropharmacology

Gen. Pharmacol.

Eur. J. Pharmacol.

Neurosci. Lett.

Jpn. J. Pharmacol.