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Modulation of neuronal activity in CNS pain pathways following propofol administration in rats: Fos and EEG analysis

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Abstract

We studied Fos expression in the central nociceptive pathways at different sedative levels in order to clarify the central mechanism of propofol’s nociceptive action. Sprague–Dawley rats received propofol (PRO) or pentobarbital (PEN) and were divided into two groups with different doses of drug administration (light and deep sedative levels) based on the electroencephalogram analysis. Rats at each sedative level received heat stimulation to their face and Fos immunohistochemistry was performed at various brain sites. We also infused lidocaine into the jugular vein to test whether PRO directly activated nociceptors distributed in the vein. Fos expression in two major ascending pain pathways (lateral and medial systems) and descending modulatory system were precisely analyzed following intravenous (i.v.) administration of PRO or PEN. Many Fos protein-like immunoreactive (Fos protein-LI) cells were expressed in the trigeminal spinal nucleus caudalis (Vc), parabrachial nucleus, parafascicular nucleus, a wide area of the primary somatosensory cortex, anterior cingulate cortex, amygdala, periaqueductal gray, solitary tract nucleus, and lateral hypothalamus following heating of the face during PRO or PEN infusion. The number of Fos protein-LI cells was significantly greater in many Central nervous system regions during PRO infusion compared with PEN. Fos expression was significantly greater in the Vc and Periaqueductal gray following greater amount of PRO infusions compared, whereas they were significantly smaller in the Vc in the rats with PEN infusion. The Fos expression was significantly depressed following i.v. infusion of lidocaine before PRO administration. The present findings suggest that PRO is involved in the enhancement of Vc activity through direct activation of the primary afferent fibers innervating veins, resulting in pain induction during infusion.

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Abbreviations

ACC:

Anterior cingulate cortex

Aq:

Aqueduct

BLA:

Basolateral amygdaroid nucleus

CNS:

Central nervous system

CeA:

Central nucleus of amygdala

EEG:

Electroencephalograph

HP:

Hypothalamus

INS:

Insular

LPBN:

Lateral parabrachial nucleus

Me5:

Mesencephalic nucleus

PAG:

Periaqueductal gray

PEN:

Pentobarbital

PF:

Parafascicular thalamic nucleus

PRO:

Propofol

Py:

Pyramis

RVM:

Rostral ventromedial medulla

SI:

Primary somatosensory cortex

SC:

Superior colliculus

SN:

Substantia nigra

Sm:

Thalamic nucleus submedius

STN:

Solitary tract nucleus

V3:

3rd ventricle

VBc:

Ventrobasal thalamic complex

Vc:

Trigeminal spinal nucleus caudalis

VLO:

Ventrolateral orbital cortex

cc:

Central canal

scp:

Superior cerebellar peduncle

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Acknowledgments

We thank Profs. R. Dubner and B. J. Sessle for invaluable comments on the manuscript. This study was supported in part by Research Grants from Sato and Uemura Funds from Nihon University School of Dentistry, and a grant from the Dental Research Center, Nihon University School of Dentistry; Nihon University multidisciplinary research grant for KI and Individual Research Grant for YT; a grant from the Ministry of Education, Culture, Sports, Science, and Technology to promote multidisciplinary research projects; a grant from the Ministry of Education, Culture, Sports, Science, and Technology to promote multidisciplinary research projects “Brain Mechanisms for Cognition, Memory and Behavior” at Nihon University. We thank Dr. D. A. Thomas for correcting English usage in the manuscript.

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Authors and Affiliations

  1. Department of Anesthesiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo , 101-8310, Japan

    Ieko Kubota, Emi Shoda & Yoshiyuki Oi

  2. Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo, 101-8310, Japan

    Yoshiyuki Tsuboi, Masahiro Kondo & Koichi Iwata

  3. Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, 101-8310, Japan

    Yoshiyuki Tsuboi, Masahiro Kondo & Koichi Iwata

  4. Division of Oral and Maxillofacial Biology, Institute for Oral Science, Matsumoto Dental University, 1780 Gobara, Hirooka, Shiojiri, Nagano, 399-0781, Japan

    Yuji Masuda

  5. Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20 Fujimi-cho, Chiyoda-ku, Tokyo, 102-8159, Japan

    Junichi Kitagawa

  6. Division of Applied System Neuroscience Advanced Medical Research Center, Nihon University Graduate School of Medical Science, 30-1 Ohyaguchi-Kamimachi Itabashi, Tokyo, 173-8610, Japan

    Koichi Iwata

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  1. Ieko Kubota
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  2. Yoshiyuki Tsuboi
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  7. Yoshiyuki Oi
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  8. Koichi Iwata
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Correspondence to Koichi Iwata.

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Kubota, I., Tsuboi, Y., Shoda, E. et al. Modulation of neuronal activity in CNS pain pathways following propofol administration in rats: Fos and EEG analysis. Exp Brain Res 179, 181–190 (2007). https://doi.org/10.1007/s00221-006-0779-x

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  • DOI: https://doi.org/10.1007/s00221-006-0779-x

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