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Effects of systemic bicuculline or morphine on formalin-evoked pain-related behaviour and c-Fos expression in trigeminal nuclei after formalin injection into the lip or tongue in rats

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Abstract

This study examined differences in nociceptive responses between lip and tongue. Formalin-induced pain-related behaviour and c-Fos expression in the trigeminal caudal nucleus (Vc) with/without systemic preadministration of a γ-aminobutyric acid (GABA) type A receptor antagonist, bicuculline (2 mg/kg, i.p., 10 min before formalin injection) or a μ-opioid receptor agonist, morphine (3 mg/kg, i.p., 10 min before formalin injection) have been studied. Formalin injection into the upper lip induced an immediate pain-related behaviour, mostly face-rubbing behaviour, for 15 min (phase 1, mean ± SEM/5 min, 81.2 ± 30.1), followed by a more increased activity for 15 min (phase 2, 205.4 ± 43.6) and a decline to baseline for next 15 min (phase 3, 63.9 ± 28.0). Formalin injection into the tongue induced similar amount of pain-related behaviour at phase 1 (67.9 ± 16.7), followed by similar activity at phase 2 (48.6 ± 6.2), and lesser behaviour at phase 3 (20.4 ± 7.6). The behaviour at phase 2 decreased following preadministration of bicuculline or morphine when formalin was injected into the lip (b, 62.5 ± 14.5; m, 95.8 ± 10.0) but not into the tongue (b, 31.0 ± 9.2; m, 77.4 ± 27.0). A considerable numbers of c-Fos-immunoreactive (IR) cells were induced in the caudal and inter-medio-lateral center of superficial layers of the Vc (VcI/II; mean ± SEM/section = 225.8 ± 12.9) and magnocellular zone of the Vc (VcIII/IV; 67.1 ± 4.7) 2 h after formalin injection into the lip. Much smaller numbers of c-Fos-IR cells were induced in the rostral and dorso-medial one-fourth of the VcI/II (72.6 ± 3.7) and VcIII/IV (55.6 ± 6.6) after formalin injection into the tongue. Following preadministration with systemic bicuculline or morphine, the formalin-induced c-Fos-IR cells were decreased more in the VcI/II when formalin was injected into the lip (VcI/II, 102.4 ± 8.0; VcIII/IV, 32.8 ± 1.4) than into the tongue (VcI/II, 49.5 ± 8.1; VcIII/IV, 31.7 ± 5.3). These results show that the lip is more sensitive to formalin-induced noxious stimulation and regulated more through GABAA and μ-opioid receptors than the tongue.

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Abbreviations

GABA:

γ-Aminobutyric acid

NK-1:

Neurokinin 1

IR:

Immunoreactive

PB:

Phosphate buffer

Spdh:

Spinal dorsal horn

TG:

Trigeminal ganglion

TSN:

Trigeminal sensory nuclei

Vc:

Trigeminal caudal nucleus

VcI/II:

Superficial layers of Vc

VcIII/IV:

Magnocellular zone of Vc

Vi:

Trigeminal interpolar nucleus

Vidm:

Dorsomedial nucleus of Vi

Vo:

Trigeminal nucleus oralis

Vodm:

Dorsomedial nucleus of Vo

Vp:

Trigeminal principal nucleus

VspTr:

Trigeminal spinal tract

WGA-HRP:

Horseradish peroxidase conjugated with wheat germ agglutinin

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Science/Sports and Culture of Japan (19592108 and 20791562). We thank Drs. Dong Wook. Kim and Daisuke Asakura for strong collaborations.

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Authors and Affiliations

  1. Department of Oral Anatomy and Neurobiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan

    S. Sugiyo, D. Uehashi, F. Satoh & Motohide Takemura

  2. Department of Dentistry and Oral Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan

    T. Abe

  3. Department of Pharmacology, Nihon University School of Dentistry, Tokyo, 101-8310, Japan

    M. Kobayashi

  4. School of Pharmaceutical Science, Ohu University, Koriyama, Fukushima, 963-8611, Japan

    N. Yonehara

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  1. S. Sugiyo
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  2. D. Uehashi
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  3. F. Satoh
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  4. T. Abe
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  5. N. Yonehara
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Correspondence to Motohide Takemura.

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Sugiyo, S., Uehashi, D., Satoh, F. et al. Effects of systemic bicuculline or morphine on formalin-evoked pain-related behaviour and c-Fos expression in trigeminal nuclei after formalin injection into the lip or tongue in rats. Exp Brain Res 196, 229–237 (2009). https://doi.org/10.1007/s00221-009-1842-1

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  • DOI: https://doi.org/10.1007/s00221-009-1842-1

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