Experimental Brain Research

, Volume 179, Issue 2, pp 181–190 | Cite as

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

  • Ieko Kubota
  • Yoshiyuki Tsuboi
  • Emi Shoda
  • Masahiro Kondo
  • Yuji Masuda
  • Junichi Kitagawa
  • Yoshiyuki Oi
  • Koichi Iwata
Research Article


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.


Sedation Nociception Trigeminal Rat Propofol 



Anterior cingulate cortex




Basolateral amygdaroid nucleus


Central nervous system


Central nucleus of amygdala








Lateral parabrachial nucleus


Mesencephalic nucleus


Periaqueductal gray




Parafascicular thalamic nucleus






Rostral ventromedial medulla


Primary somatosensory cortex


Superior colliculus


Substantia nigra


Thalamic nucleus submedius


Solitary tract nucleus


3rd ventricle


Ventrobasal thalamic complex


Trigeminal spinal nucleus caudalis


Ventrolateral orbital cortex


Central canal


Superior cerebellar peduncle


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Ieko Kubota
    • 1
  • Yoshiyuki Tsuboi
    • 2
    • 3
  • Emi Shoda
    • 1
  • Masahiro Kondo
    • 2
    • 3
  • Yuji Masuda
    • 4
  • Junichi Kitagawa
    • 5
  • Yoshiyuki Oi
    • 1
  • Koichi Iwata
    • 2
    • 3
    • 6
  1. 1.Department of AnesthesiologyNihon University School of DentistryTokyo Japan
  2. 2.Department of PhysiologyNihon University School of DentistryTokyoJapan
  3. 3.Division of Functional Morphology, Dental Research CenterNihon University School of DentistryTokyoJapan
  4. 4.Division of Oral and Maxillofacial Biology, Institute for Oral ScienceMatsumoto Dental UniversityNaganoJapan
  5. 5.Department of Physiology, School of Life Dentistry at TokyoNippon Dental UniversityTokyoJapan
  6. 6.Division of Applied System Neuroscience Advanced Medical Research CenterNihon University Graduate School of Medical ScienceTokyoJapan

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