Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

Bo Deng,Dandan Ke,Liqun Jia,Yuanyuan Wang,Lin Pan,Huangying Tan,Lili Yu,Qing Xiang,Aiping Song

doi:10.1155/2016/3629489

Abstract

One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

Highlights

Background or IntroductionOxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic colorectal cancer [1]
We examined the effects of herbal medicine Wen-luo-tong (WLT) on glial activation in the spinal dorsal horn in a rat model of OXL-induced neuropathic chronic pain
We examined the expression of excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factorα (TNF-α) in the spinal dorsal horn

Summary

Introduction

Oxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic colorectal cancer [1]. One of its main dose-limiting complications is painful neuropathy [2]. The primarily sensory symptoms occur in up to 60% of patients, and they commonly have a delayed manifestation that can linger for many years [3, 4]. The signs of neuropathy start with paresthesia, followed by hyperesthesia [5] and a heightened sensitivity to cold/low temperatures [6]. These patients suffer from both the physical symptoms and a decreased quality-of-life [1]. The presently available pain drugs only offer marginal relief due to either a lack of efficacy or the risk of unacceptable side effects [1]

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Conclusion