PMID- 29538008
OWN - NLM
STAT- MEDLINE
DCOM- 20190523
LR  - 20190523
IS  - 1365-2346 (Electronic)
IS  - 0265-0215 (Linking)
VI  - 35
IP  - 7
DP  - 2018 Jul
TI  - Toll-like receptor 4 deficient mice do not develop remifentanil-induced 
      mechanical hyperalgesia: An experimental randomised animal study.
PG  - 505-510
LID - 10.1097/EJA.0000000000000803 [doi]
AB  - BACKGROUND: Drugs with antagonistic actions on the Toll-like receptor 4 (Tlr4), 
      such as naloxone at ultra low doses, have been used to inhibit opioid-induced 
      hyperalgesia in rodents suggesting the involvement of this receptor and pathway 
      on opioid-induced hyperalgesia. OBJECTIVE: The aim of this study was to determine 
      whether mice without the Tlr4 gene (Tlr4) would not develop remifentanil-induced 
      hyperalgesia. DESIGN: An experimental randomised animal study. SETTING: 
      Experimental Unit, Complutense University of Madrid, Madrid, Spain. ANIMALS: 
      Twelve adult female wild-type mice and 12 adult Tlr4 mice. INTERVENTIONS: Under 
      sevoflurane anaesthesia, a 1-h, constant rate subcutaneous infusion of 
      remifentanil (4 mug kg min) or 0.9% saline. MAIN OUTCOME MEASURES: Mechanical 
      nociceptive thresholds were evaluated using a von Frey hair test before 
      (baseline) and on days 5, 6 and 7 after treatment. Hyperalgesia was considered to 
      be a decrease in the mechanical nociceptive threshold. Changes in mechanical 
      nociceptive thresholds in the different groups were compared with one-sided 
      paired t tests. RESULTS: Baseline mechanical nociceptive thresholds were similar 
      in all groups (2.2 +/- 0.1 g). Remifentanil produced a 24% decrease in mechanical 
      nociceptive thresholds in the wild-type mice (1.7 +/- 0.0 g, averaged over 3 days, 
      P = 0.00021), whereas the nociceptive thresholds were not changed in Tlr4 mice 
      (2.2 +/- 0.1 g, P = 0.857) or in mice receiving 0.9% saline (Tlr4, 2.2 +/- 0.1 g, 
      P = 0.807; wild-type, 2.2 +/- 0.1 g, P = 0.962). CONCLUSION: Tlr4 receptor 
      involvement is suggested in the development of remifentanil-induced hyperalgesia 
      in mice. TRIAL REGISTRATION: CEA-UCM 107/2012.
FAU - Aguado, Delia
AU  - Aguado D
AD  - From the Department of Animal Medicine and Surgery, Veterinary Faculty, 
      Complutense University of Madrid (UCM), Madrid, Spain (DA, RB, IAG).
FAU - Bustamante, Rocio
AU  - Bustamante R
FAU - Gomez de Segura, Ignacio A
AU  - Gomez de Segura IA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Anaesthesiol
JT  - European journal of anaesthesiology
JID - 8411711
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - P10582JYYK (Remifentanil)
SB  - IM
MH  - Analgesics, Opioid/*toxicity
MH  - Animals
MH  - Female
MH  - Hyperalgesia/*chemically induced/*metabolism
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Physical Stimulation/adverse effects
MH  - Random Allocation
MH  - Remifentanil/*toxicity
MH  - Toll-Like Receptor 4/*deficiency/genetics
EDAT- 2018/03/15 06:00
MHDA- 2019/05/24 06:00
CRDT- 2018/03/15 06:00
PHST- 2018/03/15 06:00 [pubmed]
PHST- 2019/05/24 06:00 [medline]
PHST- 2018/03/15 06:00 [entrez]
AID - 10.1097/EJA.0000000000000803 [doi]
PST - ppublish
SO  - Eur J Anaesthesiol. 2018 Jul;35(7):505-510. doi: 10.1097/EJA.0000000000000803.