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.

HES-B and HES-C are equally retained in the blood vessels. Middle-sized HES-B with low DS and middle substitution pattern stayed in the blood vessels as long as the large-sized HES. HES solutions of varying characters should be examined to optimize HES infusion.

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 two 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 regulated-kinase (pERK) immunohistochemistry were performed in subnucleus caudalis (Vc) and upper cervical spinal cord. 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) in the rats with PEN or PRO administration 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 injection than those with PEN injection. 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 dominantly distributed in the Vi/Vc, middle Vc and Vc/C2 after the bolus injections of PRO. The expression of pERK-LI cells was depressed after the intravenous lidocaine application before PRO injection. The present findings suggested 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 injection of PRO.*To whom all correspondence should be addressed. Telephone number: +81 -3 -3219 -8112 Fax number: +81 -3 -3219 -8341 e-mail address: E-mail: iwata-k@dent.nihon-u.ac.jp. 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 injection. 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. NIH Public AccessAuthor Manuscript J Pain. Author manuscript; available in PMC 2010 June 1.

No abstract

Propofol (PRO) is frequently used as the reliable sedative agent in clinic situation because it is safe and easy to control the depth of sedative level. PRO, however, has weak analgesic action even causing acute pain sensation during intravenous infusion. For the clinical use of sedatives, the invasive action such as pain should be relieved. It is very important to know underlying mechanisms of the weak analgesic action of propofol in order to improve clinical use of PRO. We studied the phosphorylated Extracellular Signal-regulated Kinase (pERK) expression in the trigeminal spinal nucleus and upper cervical nociceptive neurons to clarify the central mechanism of the enhancement of trigeminal transmission. We observed that a large number of pERK-LI cells were expressed in Vi/Vc zone, middle Vc and Vc-C2 zone immediately after the large amount of propofol injection. The number of pERK-LI cells was increased following increase in the amount of PRO administration. We also observed that the expression of pERK-LI cells was depressed after the lidocaine injection before PRO injection. The present findings suggest that PRO has a strong ability to enhance nociceptive neuronal activity in the trigeminal region through the primary afferent nociceptors innervated in the cervical vein, resulting in the central sensitization of the trigeminal nociceptive pathways during infusion.