title: Sensitization of the transient receptor potential vanilloid type 1 ion channel by isoflurane or sevoflurane does not result in extracellular signal-regulated kinase 1/2 activation in rat spinal dorsal horn neurons.
abstract: Clinically relevant concentrations of isoflurane or sevoflurane sensitize transient receptor potential vanilloid type 1 to several of its activators, including capsaicin. It has, moreover, been suggested these volatile general anaesthetics may augment nociceptive signalling arising from surgical procedures and thereby contribute to post-operative pain. To investigate this suggestion, we have studied intraplantar capsaicin injection-induced phosphorylation of extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons (which is a recognized marker of spinal nociceptive processing) in rat during isoflurane or sevoflurane anaesthesia after 60 min under anaesthesia. Control animals were anaesthetized with pentobarbital (which of itself does not activate extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons). Unilateral intraplantar capsaicin injection in control animals evoked extracellular signal-regulated kinase 1/2 phosphorylation in a group of neurons in lamina I and lamina II of the ipsilateral spinal dorsal horn in a somatotopically appropriate area. In contrast, both anaesthetic gases (given for 60 min and without subsequent capsaicin injection) induced extracellular signal-regulated kinase 1/2 activation in a different group of mainly lamina I neurons bilaterally. The total number of spinal dorsal horn neurons labelled on the ipliateral side following capsaicin injection into the isoflurane-, or sevoflurane-, anaesthetized animals was significantly less than that produced by capsaicin alone. Further, capsaicin injection into isoflurane-, or sevoflurane-, anaesthetized animals reduced extracellular signal-regulated kinase 1/2 phosphorylation induced by the gases alone on both sides. These findings do not support the suggestion that isoflurane-, or sevoflurane-, induced sensitization of transient receptor potential vanilloid type 1 by capsaicin, or other agonist, is translated into induction of spinal nociceptive processing and consequential pain sensation.
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, 369, Fulham Road, London SW10 9NH, UK.
authors.forename: J P M
authors.initials: JP
authors.lastname: White
authors.forename: M
authors.initials: M
authors.lastname: Cibelli
authors.forename: A R
authors.initials: AR
authors.lastname: Fidalgo
authors.forename: C C
authors.initials: CC
authors.lastname: Paule
authors.forename: P J
authors.initials: PJ
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Jenes
authors.forename: A S C
authors.initials: AS
authors.lastname: Rice
authors.forename: I
authors.initials: I
authors.lastname: Nagy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D007150:Immunohistochemistry; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D020671:Posterior Horn Cells / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D008738:Methyl Ethers; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D000077149:Sevoflurane; D007530:Isoflurane; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3