Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel-specific modulator, in rats

The Journal of Headache and Pain

Research Article

Zhi-Yong Tan¹  Yong-Hua Ji²  Pin Ye²  Bin Wu²  Zheng-Wei Li² 

[1] Department of Pharmacology and Toxicology and Stark Neurosciences Research Institute, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, 200436, Shanghai, People’s Republic of China;

关键词: Dorsal Root Ganglion;    Brain Natriuretic Peptide;    Dorsal Root Ganglion Neuron;    Inflammatory Pain;    Pain Behavior;   

DOI  :  10.1186/s10194-016-0685-y

 received in 2016-07-10, accepted in 2016-09-24,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundA previous study found that brain natriuretic peptide (BNP) inhibited inflammatory pain via activating its receptor natriuretic peptide receptor A (NPRA) in nociceptive sensory neurons. A recent study found that functional NPRA is expressed in almost all the trigeminal ganglion (TG) neurons at membrane level suggesting a potentially important role for BNP in migraine pathophysiology.MethodsAn inflammatory pain model was produced by subcutaneous injection of BmK I, a sodium channel-specific modulator from venom of Chinese scorpion Buthus martensi Karsch. Quantitative PCR, Western Blot, and immunohistochemistry were used to detect mRNA and protein expression of BNP and NPRA in dorsal root ganglion (DRG) and dorsal horn of spinal cord. Whole-cell patch clamping experiments were conducted to record large-conductance Ca2+-activated K+ (BKCa) currents of membrane excitability of DRG neurons. Spontaneous and evoked pain behaviors were examined.ResultsThe mRNA and protein expression of BNP and NPRA was up-regulated in DRG and dorsal horn of spinal cord after BmK I injection. The BNP and NPRA was preferentially expressed in small-sized DRG neurons among which BNP was expressed in both CGRP-positive and IB4-positive neurons while NPRA was preferentially expressed in CGRP-positive neurons. BNP increased the open probability of BKCa channels and suppressed the membrane excitability of small-sized DRG neurons. Intrathecal injection of BNP significantly inhibited BmK-induced pain behaviors including both spontaneous and evoked pain behaviors.ConclusionsThese results suggested that BNP might play an important role as an endogenous pain reliever in BmK I-induced inflammatory pain condition. It is also suggested that BNP might play a similar role in other pathophysiological pain conditions including migraine.

【 授权许可】

CC BY   
© The Author(s). 2016