title: Increased phosphorylation of extracellular signal-regulated kinase in trigeminal nociceptive neurons following propofol administration in rats.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Shoda
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitagawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Suzuki
authors.forename: Ieko
authors.initials: I
authors.lastname: Nitta-Kubota
authors.forename: Makiko
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kondo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Masuda
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Oi
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D001921:Brain / Q000187:drug effects; D002211:Capsaicin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008012:Lidocaine / Q000008:administration & dosage; D008297:Male; D009619:Nociceptors / Q000187:drug effects* / Q000201:enzymology; D010424:Pentobarbital / Q000494:pharmacology; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000008:administration & dosage; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000779:Anesthetics, Local; D006993:Hypnotics and Sedatives; D018689:Sensory System Agents; D008012:Lidocaine; D048049:Extracellular Signal-Regulated MAP Kinases; D010424:Pentobarbital; D002211:Capsaicin; D015742:Propofol