Akanuma Yuko, Kato Mami, Takayama Yasunori, Ikemoto Hideshi, Adachi Naoki, Ohashi Yusuke, Yogi Wakako, Okumo Takayuki, Tsukada Mana, Sunagawa Masataka
Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan.
Department of Anesthesiology, St. Luke's International Hospital, Tokyo 104-8560, Japan.
Medicines (Basel). 2020 Dec 17;7(12):75. doi: 10.3390/medicines7120075.
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 (YKS). 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. 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. These findings suggest that YKS could reduce the use of fentanyl and combined use of YKS and fentanyl is considered clinically useful.
当以单次高剂量给药时，芬太尼可诱导急性阿片类药物耐受性和术后痛觉过敏；因此，本研究考察了芬太尼与（YKS）联合使用的镇痛效果。将大鼠分为对照组、注射福尔马林组（FOR）、YKS治疗+FOR组（YKS）、芬太尼治疗+FOR组（FEN）和YKS+FEN+FOR组（YKS+FEN）。通过向爪部皮下注射福尔马林诱导急性疼痛。测量与疼痛相关行为的持续时间。在早期（0 - 10分钟）和中期（10 - 20分钟），与FOR组相比，YKS+FEN组的疼痛相关行为受到显著抑制。在后期（20 - 60分钟），FEN组的疼痛相关行为持续时间最长，与YKS组相比显著增加。我们探究了对脊髓细胞外信号调节激酶（ERK）通路的影响，YKS可抑制磷酸化ERK表达，这可能与YKS在后期的镇痛作用有关。这些发现表明，YKS可减少芬太尼的使用，YKS与芬太尼联合使用在临床上被认为是有用的。
