Abstract
Although propofol (PRO) is widely used in clinic as a hypnotic agent, the underlying
mechanisms of its action on pain pathways is still unknown. Sprague-Dawley rats were
assigned to receive PRO or pentobarbital (PEN) and were divided into 2 groups as LIGHT
and DEEP hypnotic levels based on the EEG analysis. Rats in each hypnotic level received
capsaicin injection into the face and phosphorylated extracellular signal-regulated
kinase (pERK) immunohistochemistry was performed in subnucleus caudalis (Vc) and upper
cervical spinal cord. In the rats with PEN or PRO administration, a large number of
pERK-like immunoreactive (LI) cells was observed in the trigeminal spinal subnuclei
interpolaris and caudalis transition zone (Vi/Vc), middle Vc, and transition zone
between Vc and upper cervical spinal cord (Vc/C2) following capsaicin injection into
the whisker-pad region. The number of pERK-LI cells in Vi/Vc, middle Vc, and Vc/C2
was significantly larger in rats with PRO infusion than those with PEN infusion. The
number of pERK-LI cells was increased following an increase in the dose of PRO but
not in PEN. The pERK-LI cells were mainly distributed in the Vi/Vc, middle Vc, and
Vc/C2 after the bolus infusion of PRO. The expression of pERK-LI cells was depressed
after the intravenous lidocaine application before bolus PRO infusion. The present
findings suggest that PRO induced an enhancement of the activity of trigeminal nociceptive
pathways through nociceptors innervating the venous structure, as indicated by a lidocaine-sensitive
increase in pERK. This may explain deep pain around the injection regions during intravenous
bolus infusion of PRO.
Perspective
The effect of propofol administration on ERK phosphorylation in the subregions of
the spinal trigeminal complex and upper cervical spinal cord neurons were precisely
analyzed in rats with PRO infusion. A large number of pERK-LI cells was observed following
intravenous PRO administration, suggesting an enhancement of trigeminal nociceptive
activity and that PRO may produce pain through nociceptors innervating the venous
structures during infusion.
Key words
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Article info
Publication history
Published online: April 24, 2009
Accepted:
November 18,
2008
Received in revised form:
November 13,
2008
Received:
March 10,
2008
Footnotes
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; 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. K.R. is supported by NIH Grant DE11964.
Identification
Copyright
© 2009 American Pain Society. Published by Elsevier Inc. All rights reserved.
