| Summary: | <b>Background:</b> Japanese herbal medicine, called Kampo medicine, and acupuncture are mainly used in Japanese traditional medicine. In this experiment, the analgesic effect of <i>Yokukansan</i> (YKS) alone and a combination of YKS and electroacupuncture (EA) on inflammatory pain induced by formalin injection were examined. <b>Methods:</b> Animals were divided into four groups: a control group, formalin injection group (formalin), YKS-treated formalin group (YKS), and YKS- and EA-treated formalin group (YKS + EA). The duration of pain-related behaviors and extracellular signal-regulated protein kinase (ERK) activation in the spinal cord after formalin injection in the right hind paw were determined. <b>Results:</b> The duration of pain-related behaviors was dramatically prolonged in the late phase (10–60 min) in the formalin group. The YKS treatment tended to reduce (<i>p</i> = 0.08), whereas YKS + EA significantly suppressed the pain-related behaviors (<i>p</i> < 0.01). Immunohistochemical and Western blot analyses revealed that the number of phosphorylated ERK1/2 (pERK1/2)-positive cells and the pERK expression level, which were increased by formalin injection, were significantly inhibited by YKS (<i>p</i> < 0.05) and YKS + EA (<i>p</i> < 0.01). <b>Conclusions:</b> The YKS + EA combination therapy elicited an analgesic effect on formalin-induced acute inflammatory pain.
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