Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model, and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice.

Xiaolin Su,Yong-Hua Ji,Wentong Zhang,Bin Wu,Qiuhong Wang,Zhi-Yong Tan

doi:10.3389/fphar.2019.01522

Abstract

Radix angelicae pubescentis (RAP) has been used in Chinese traditional medicine to treat painful diseases such as rheumatism and headache. A previous study has reported that columbianadin (CBN), a major coumarin in RAP inhibits acute and inflammatory pain behaviors. However, the effects of CBN on neuropathic pain behaviors, and the potential underlying mechanism have not been reported. In the present study, the effects of CBN, compared to another major coumarin of RAP osthole (OST), on oxaliplatin-induced neuropathic pain behaviors and on the voltage-gated calcium currents in small dorsal root ganglion (DRG) neurons were studied in mice. It was found that CBN and OST inhibited both mechanical and cold hypersensitivity induced by oxaliplatin. Moreover, CBN and OST might preferentially inhibit T- and L-type calcium currents (Ica). The inhibitory effects of CBN and OST on the oxaliplatin-induced mechanical allodynia were prevented by gabapentin. These results suggest that CBN, as well as OST might inhibit neuropathic pain behaviors through an inhibition of T- and L-type calcium currents in nociceptive DRG neurons.

Highlights

Radix angelicae pubescentis (RAP) is the dried roots of Angelica pubescens Maxim
We examined the effects of CBN, compared to OST, on mechanical allodynia and thermal hyperalgesia in a neuropathic pain model associated with a chemotherapy drug oxaliplatin
We first studied the effects of CBN and OST on the nociceptive behaviors in a mouse model of neuropathic pain induced by oxaliplatin

Summary

Introduction

Radix angelicae pubescentis (RAP) is the dried roots of Angelica pubescens Maxim. Freziera biserrata Shan et Yuan (family Umbelliferae) and was initially described in Shennong Ben Cao Jing as a traditional Chinese medicine. A major coumarin in RAP osthole (OST) inhibits pain behaviors in multiple pain models such as inflammatory pain, diabetic pain, and low back pain models (Chen et al, 1995; Wu et al, 2017; Singh et al, 2018; Yuan et al, 2018) These results suggested that OST is an anti-nociceptive component in RAP. Columbianadin (CBN) is another major coumarin in RAP and there is one study so far reported that CBN inhibits acute and inflammatory pain behaviors (Chen et al, 1995; Chinese Pharmacopoeia Commission, 2015). Neither the potential mechanism underlying the anti-nociceptive effects of CBN nor if CBN modulates ion channels has been reported

Objectives

Methods

Results

Conclusion