title: Emulsified isoflurane enhances thermal transient receptor potential vanilloid-1 channel activation-mediated sensory/nociceptive blockade by QX-314.
abstract: BACKGROUND
  QX-314 produces nociceptive blockade, facilitated by permeation through transient receptor potential vanilloid-1 (TRPV1) channels. TRPV1 channel can be activated by noxious heat and sensitized by volatile anesthetics. The authors hypothesized that emulsified isoflurane (EI) could enhance thermal TRPV1 channel activation-mediated sensory/nociceptive blockade by QX-314.
  
  
  METHODS
  Rats were perineurally injected with QX-314 (Sigma-Aldrich Co. Ltd. Shanghai, China) alone or QX-314 combined with EI, followed by heat exposure on the injection site. The tail-flick and tail-clamping tests were used to assess sensory and nociceptive blockade, respectively; a sciatic nerve block model was used to assess motor and sensory blockade. Effects of EI on thermal activation of TRPV1 channels were evaluated on rat dorsal root ganglia neurons by whole-cell patch-clamp recordings.
  
  
  RESULTS
  Heat exposure enhanced sensory/nociceptive blockade by QX-314 in rat tails, but not motor blockade in sciatic nerve block model. QX-314 alone or QX-314 + 42°C produced no nociceptive blockade. QX-314 + 48°C produced 100% nociceptive blockade with duration of 12.5 ± 2.0 h (mean ± SEM). By adding 2% EI, QX-314 + 42°C produced 80% nociceptive blockade with duration of 8.1 ± 1.9 h, which was similar to the effect of QX-314 + 46°C (7.7 ± 1.1 h; P = 0.781). The enhancement of heat on sensory/nociceptive blockade of QX-314 was prevented by TRPV1 channel antagonist. The temperature thresholds of TRPV1 channel activation on dorsal root ganglia neurons were significantly reduced by EI.
  
  
  CONCLUSIONS
  Thermal activation of TRPV1 channels enhanced long-lasting sensory/nociceptive blockade by QX-314 without affecting motor blockade. The addition of EI reduced temperature thresholds for inducing long-lasting sensory/nociceptive blockade due to QX-314.
authors.affiliation: From the Laboratory of Anesthesia and Critical Care Medicine (C.Z., J.L., W.Z., D.L., Y.C., X.C., T.L.), Department of Anesthesiology (P.L., J.L., W.Z., X.C.), Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Liang
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
authors.forename: Daqing
authors.initials: D
authors.lastname: Liao
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D005727:Ganglia, Spinal / Q000187:drug effects; D006358:Hot Temperature; D007530:Isoflurane / Q000008:administration & dosage* / Q000494:pharmacology*; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects; D009407:Nerve Block; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D010743:Phospholipids; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000187:drug effects*; D013024:Soybean Oil; D050916:TRPV Cation Channels / Q000187:drug effects*; D013623:Tail / Q000187:drug effects / Q000294:innervation
chemical_list: D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D010743:Phospholipids; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C545823:soybean oil, phospholipid emulsion; C012647:QX-314; D013024:Soybean Oil; D008012:Lidocaine; D007530:Isoflurane