Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: A mouse model study

Abstract

Abstract Background Yokukansan (YKS), a traditional Japanese medicine (Kampo), has been widely used to treat neurosis, dementia, and chronic pain. Previous in vitro studies have suggested that YKS acts as a partial agonist of the 5-HT1A receptor, resulting in amelioration of chronic pain through inhibition of nociceptive neuronal activity. However, its effectiveness for treating postoperative pain remains unknown, although its analgesic mechanism of action has been suggested to involve serotonin and glutamatergic neurotransmission. This study aimed to investigate the effect of YKS on postoperative pain in an animal model. Methods A mouse model of postoperative pain was created by plantar incision, and YKS was administered orally the day after paw incision. Pain thresholds for mechanical and heat stimuli were examined in a behavioral experiment. In addition, to clarify the involvement of the serotonergic nervous system, we examined the antihyperalgesic effects of YKS in mice that were serotonin-depleted by para-chlorophenylalanine (PCPA) treatment. Results Serotonin immunoreactivity in the spinal dorsal horn was entirely abolished by PCPA pretreatment; however, it did not change the pain threshold after paw incision. YKS increased the pain threshold in a dose-dependent manner, whereas the antihyperalgesic effect of YKS was significantly attenuated by PCPA as compared with that in postoperative pain model mice without PCPA treatment. Conclusion In this study, we revealed that oral administration of YKS had acute analgesic effects in a mouse model of postoperative pain, and our behavioral experiments using serotonin-depleted mice suggested that YKS acts as a partial agonist of one of the serotonin receptors.