The Analgesic and Anti-Stress Effects of a Kampo Medicine (Yokukansan) in Rats with Chronic Constriction Injury ? A Comparative Study with Kamishoyosan

Background: Yokukansan (YKS), which is a Japanese traditional herbal (Kampo) medicine, is composed of seven crude drugs: Uncariae cum uncis ramulus, Cnidii rhizoma, Bupleuri radix, Atractylodis lanceae rhizoma, Poria, Angelicae radix and Glycyrrhizae radix. Although YKS is typically administered to patients with symptoms such as emotional irritability and neurosis, it has also recently been reported to be effective against pain disorders. Kamishoyosan (KSS), which contains similar component galenicals to YKS, is used to treat neuropsychiatric symptoms. The present study investigated the effects of these medicines on neuropathic pain and the stress caused by pain. Methods: The present study used a rat model of chronic constriction injury (CCI). At week 2 post-CCI, decreases in the mechanical and thermal withdrawal thresholds were confirmed in the CCI rats and the drugs were administered for a two-week period. At week 4 post-CCI, the levels of plasma corticosterone and chromogranin A, which are markers of mental stress, were measured to evaluate the anti-stress effects. Furthermore, we investigated the changes in pain threshold and spinal astrocytes, which are involved in the expression of chronic pain, to evaluate the analgesic effects. Results: The levels of plasma corticosterone and chromogranin A significantly increased in the CCI rats. Moreover, the pain threshold significantly decreased and the activation of the spinal astrocytes was observed. The increases in the levels of corticosterone and chromogranin A were significantly suppressed by the administration of either YKS or KSS. However, the control of astrocytic activation and the decrease in the pain threshold only occurred after the administration of YKS. Conclusion: The results indicate that YKS effectively reduces both the stress caused by pain and neuropathic pain.