Analgesic Efficacy of a Combination of Fentanyl and a Japanese Herbal Medicine " Yokukansan" in Rats with Acute Inflammatory Pain

Yuko Akanuma; Mami Kato; Yasunori Takayama; Hideshi Ikemoto; Naoki Adachi; Yusuke Ohashi; Wakako Yogi; Takayuki Okumo; Mana Tsukada; Masataka Sunagawa

doi:10.3390/medicines7120075

Analgesic Efficacy of a Combination of Fentanyl and a Japanese Herbal Medicine " Yokukansan" in Rats with Acute Inflammatory Pain

Medicines (Basel). 2020 Dec 17;7(12):75. doi: 10.3390/medicines7120075.

Authors

Yuko Akanuma^{1

2}, Mami Kato¹, Yasunori Takayama¹, Hideshi Ikemoto¹, Naoki Adachi¹, Yusuke Ohashi^{1

3}, Wakako Yogi^{1

4}, Takayuki Okumo¹, Mana Tsukada¹, Masataka Sunagawa¹

Affiliations

¹ Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan.
² Department of Anesthesiology, St. Luke's International Hospital, Tokyo 104-8560, Japan.
³ Department of Palliative Medicine, Showa University Yokohama Northern Hospital, Kanagawa 224-8503, Japan.
⁴ Pharmaceutical Department, Showa University Hospital, Tokyo 142-8666, Japan.

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.

Keywords: Yokukansan; fentanyl; herbal medicine; phosphorylated extracellular signal-regulated kinase (pERK); transient receptor potential ankyrin 1 (TRPA1) channel; whole-cell patch-clamp recording.