Gyejigachulbu-Tang Relieves Oxaliplatin-Induced Neuropathic Cold and Mechanical Hypersensitivity in Rats via the Suppression of Spinal Glial Activation.

Byung-Soo Ahn,Deog Sang Hwang,Seong-Kyu Kim,Ji-Hye Lee,Ha Neul Kim,Sun Kwang Kim,Hyunsu Bae,Byung-Il Min,Ji-Hwan Lee

doi:10.1155/2014/436482

Abstract

Activation of spinal glial cells plays a crucial role in the pathogenesis of neuropathic pain. An administration of oxaliplatin, an important anticancer drug, often induces acute neuropathic cold hypersensitivity and/or mechanical hypersensitivity in patients. Gyejigachulbu-tang (GBT), a herbal formula comprising Cinnamomi Cortex, Paeoniae Radix, Atractylodis Lanceae Rhizoma, Zizyphi Fructus, Glycyrrhizae Radix, Zingiberis Rhizoma, and Aconiti Tuber, has been used in East Asia to treat various pain symptoms, especially in cold patients. This study investigated whether and how GBT alleviates oxaliplatin-induced cold and mechanical hypersensitivity in rats. The behavioral signs of cold and mechanical hypersensitivity were evaluated by a tail immersion test in cold water (4°C) and a von Frey hair test, respectively. The significant cold and mechanical hypersensitivity were observed 3 days after an oxaliplatin injection (6 mg/kg, i.p.). Daily oral administration of GBT (200, 400, and 600 mg/kg) for 5 days markedly attenuated cold and mechanical hypersensitivity. Immunoreactivities of glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker) in the spinal dorsal horn were significantly increased by an oxaliplatin injection, which were restored by GBT administration. These results indicate that GBT relieves oxaliplatin-induced cold and mechanical hypersensitivity in rats possibly through the suppression of spinal glial activation.

Highlights

Oxaliplatin is a third-generation platinum-based chemotherapy drug that has gained importance in the treatment of advanced colorectal cancer [1, 2]
We investigated whether GBT relieves oxaliplatin-induced cold and mechanical hypersensitivity and if so, whether such antiallodynic effects of GBT are related to the modulation of spinal glial activation
On the 3rd day after an oxaliplatin injection, there was no significant difference in cold and mechanical sensitivity between the normal saline-administered control group and GBT-administered groups, slight increases in tail withdrawal latency and mechanical threshold were observed after GBT treatments

Summary

Introduction

Oxaliplatin is a third-generation platinum-based chemotherapy drug that has gained importance in the treatment of advanced colorectal cancer [1, 2]. Unlike the other platinum compounds (e.g., cisplatin), oxaliplatin does not induce a nephrotoxicity but often induces a very acute painful neuropathy even from a single administration [3]. This acute neurotoxic side effect, the only major dose-limiting toxicity associated with oxaliplatin use [4], is characterized by the rapid onset of spontaneous severe pain and cold hypersensitivity in the hands, feet, perioral area, or throat [5,6,7]. Many lines of evidence have revealed that spinal astrocytes and microglia change their morphology and function following peripheral nerve damage

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Conclusion