Toll-like receptor 4 deficient mice do not develop remifentanil-induced mechanical hyperalgesia: An experimental randomised animal study

Autor: Rocío Bustamante, Ignacio A. Gómez de Segura, Delia Aguado
Rok vydání: 2018
Předmět:
Zdroj: European journal of anaesthesiology. 35(7)
ISSN: 1365-2346
Popis: 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 μg 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.
Databáze: OpenAIRE