Yokukansan Improves Mechanical Allodynia through the Regulation of Interleukin-6 Expression in the Spinal Cord in Mice with Neuropathic Pain.

Shigeru Ebisawa,Tsugunobu Andoh,Yasushi Kuraishi,Yutaka Shimada

doi:10.1155/2015/870687

Shigeru Ebisawa, Tsugunobu Andoh + Show 2 more

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https://doi.org/10.1155/2015/870687

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Abstract

Neuropathic pain is caused by nerve injury. Yokukansan (Yi-Gan San), a traditional Japanese (Kampo) medicine, has been widely used for neuropathic pain control. However, the analgesic mechanisms remain unknown. In this study, we investigated the analgesic mechanisms of yokukansan in a mouse model of neuropathic pain. Partial sciatic nerve ligation (PSL) induced mechanical allodynia in mice. Repetitive oral administration of the extracts of yokukansan and the constituent herbal medicine Atractylodis Lanceae Rhizoma, but not Glycyrrhizae Radix, relieved mechanical allodynia in the PSL mice and inhibited the PSL-induced expression of interleukin- (IL-) 6 mRNA in the spinal cord. Yokukansan did not attenuate intrathecal IL-6-induced mechanical allodynia. IL-6 immunoreactivity was detected in microglia and astrocytes in the spinal dorsal horn. These results suggest that yokukansan relieves mechanical allodynia in PSL mice by regulating the expression of IL-6 in astrocytes and/or microglia in the spinal cord. In addition, the components of Atractylodis Lanceae Rhizoma, one of the constituent herbal medicines in yokukansan, may play an important role in the regulation of IL-6 expression and neuropathic pain control.

Highlights

Neuropathic pain is primarily induced by sensory nerve damage and is very difficult to control
Our preliminary experiment showed that keishikajutsubuto attenuates mechanical allodynia in partial sciatic nerve ligation (PSL) mice
We investigated the antiallodynic effects of the extracts of Glycyrrhizae Radix and Atractylodis Lanceae Rhizoma, which are components of both yokukansan and keishikajutsubuto

Summary

Introduction

Neuropathic pain is primarily induced by sensory nerve damage and is very difficult to control. Several animal models of neuropathic pain have been developed [1] and evaluated, with the findings indicating that ATP, cytokines (e.g., interleukin- (IL-) 6, IL-1β, and tumor necrosis factor alpha), nitric oxide, prostaglandins, and brain-derived neurotrophic factor released from microglia and astrocytes in the spinal cord contribute to neuropathic pain [2]. Yokukansan is used to control nighttime crying in children and to treat insomnia and neurosis. Recent reports showed that yokukansan controls hallucinations and aggravation of dementia-associated symptoms and neuropathic pain [3, 4]. The inhibitory mechanisms of yokukansan for the control of neuropathic pain remain unclear. In the present study, we investigated the therapeutic effects of yokukansan on neuropathic pain and the underlying mechanisms in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL)

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