Effect of Kamishoyosan on Primary Dysmenorrhea Pain

Dysmenorrhea refers to pathological symptoms that occur in association with menstruation during the menstrual period. Treatment options for dysmenorrhea include nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose estrogen-progestin combination pills. However, some patients do not respond to these treatments, and long-term use can lead to adverse reactions, raising additional problems. To overcome these issues, Kampo (traditional Japanese herbal) medicines are often used, with prescriptions based on Kampo medicine diagnoses. In this study, we investigated the analgesic effects of Kamishoyosan, a Kampo medicine frequently used to treat this disease, using a mouse primary dysmenorrhea (PD) model. Since Kamishoyosan is typically administered over a long term in clinical settings, we also evaluated its effects on PD after single-dose or repeated long-term administration. Oxytocin administration to continuously estradiol-treated mice significantly increased the number of writhing responses (an index of pain), uterine tissue level of prostaglandin F2α (PGF2α), and calcium ion (Ca²⁺) level, while uterine blood flow significantly decreased. In contrast, repeated administration of Kamishoyosan decreased the number of writhing responses. The uterine tissue PGF2α and Ca²⁺ levels reduced after single-dose administration at a high dose and regardless of dosage after repeated administration. Uterine blood flow was improved by single-dose administration regardless of dosage. These results showed that continuous administration of Kamishoyosan exerted analgesic effects on PD symptoms even at non-high doses. Furthermore, Kamishoyosan may reduce PD-related pain by acting on uterine contraction factor (including PG)-producing pathways and uterine blood flow.