Abstract
Background: Fentanyl can induce acute opioid tolerance and postoperative hyperalgesia when administered at a single high dose; thus, this study examined the analgesic efficacy of a combination of fentanyl and Yokukansan (YKS). Methods: Rats were divided into control, formalin-injected (FOR), YKS-treated+FOR (YKS), fentanyl-treated+FOR (FEN), and YKS+FEN+FOR (YKS+FEN) groups. Acute pain was induced via subcutaneous injection of formalin into the paw. The time engaged in pain-related behavior was measured. Results: In the early (0–10 min) and intermediate (10–20 min) phases, pain-related behavior in the YKS+FEN group was significantly inhibited compared with the FOR group. In the late phase (20–60 min), pain-related behavior in the FEN group was the longest and significantly increased compared with the YKS group. We explored the influence on the extracellular signal-regulated kinase (ERK) pathway in the spinal cord, and YKS suppressed the phosphorylated ERK expression, which may be related to the analgesic effect of YKS in the late phase. Conclusions: These findings suggest that YKS could reduce the use of fentanyl and combined use of YKS and fentanyl is considered clinically useful.
Highlights
Fentanyl and remifentanil are potent ultra-short-acting μ-opioid receptor agonists widely used for pain management in the perioperative period [1]
It is reported that 0.04 μg/kg of fentanyl has no effect on formalin-induced pain and 0.16 μg/kg significantly inhibits it [38]
The present study examined the analgesic effect of a combination of fentanyl and YKS using a rat model of acute inflammatory pain
Summary
Fentanyl and remifentanil are potent ultra-short-acting μ-opioid receptor agonists widely used for pain management in the perioperative period [1]. Their use is limited because they can induce acute opioid tolerance and a post-treatment state of heightened pain sensitivity, known as opioid-induced hyperalgesia (OIH), when administered at a single high dose [2,3,4,5]. Fentanyl can induce acute opioid tolerance and postoperative hyperalgesia when administered at a single high dose; this study examined the analgesic efficacy of a combination of fentanyl and Yokukansan (YKS). In the late phase (20–60 min), pain-related behavior in the FEN group was the longest and significantly increased compared with the YKS group. Conclusions: These findings suggest that YKS could reduce the use of fentanyl and combined use of YKS and fentanyl is considered clinically useful
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