8月11日，中国科学院上海生命科学研究院神经科学研究所的博士研究生张方雄及合作者在张旭研究员指导下完成的研究成果得以发表。此项成果主要是激活伤害性感觉神经元中B型钠尿肽/钠尿肽受体A信号通路抑制炎性痛。
背根节中的伤害性感觉神经元是痛觉传导通路的第一站，伤害性刺激使这些神经元的传入纤维释放谷氨酸等兴奋性神经递质，向脊髓及大脑传递痛觉信息。张旭研究组首先发现外周组织炎症可以显着增加伤害性感觉神经元中B型钠尿肽及其受体钠尿肽受体A的基因表达，随后他们观察到在谷氨酸作用条件下，B型钠尿肽通过增加大电导钙激活性钾离子通道的开放概率来降低伤害性感觉神经元的兴奋性，对痛觉信息传入起抑制作用。在脊髓腔内注射B型钠尿肽可显着地抑制急性和慢性炎症痛。
因此，由伤害性感觉传入纤维分泌的B型钠尿肽通过激活位于突触前的钠尿肽受体A对兴奋性突触传递起抑制性调节作用，该研究还提示激活伤害性感觉神经元中的B型钠尿肽/钠尿肽受体A信号转导通路有可能是一种新的镇痛策略。
该工作得到了科学院、科技部和国家自然科学基金的资助。（生物谷Bioon.com）
揭密疼痛的感觉与机理
Nature Medicine：Resolvins或是治疗炎症疼痛的新型镇痛药
Psychological Science：思念爱人可缓解疼痛
Nature：与慢性疼痛有关的传感神经元
计算机软件减轻患者疼痛
生物谷推荐原文出处：
The Journal of Neuroscience doi:10.1523/JNEUROSCI.0657-10.2010
Inhibition of Inflammatory Pain by Activating B-Type Natriuretic Peptide Signal Pathway in Nociceptive Sensory Neurons
Fang-Xiong Zhang,1 Xing-Jun Liu,1 Li-Qin Gong,1 Jun-Ru Yao,1 Kai-Cheng Li,1 Zi-Yan Li,2 Li-Bo Lin,3 Ying-Jin Lu,1 Hua-Sheng Xiao,3 Lan Bao,2 Xiao-Hui Zhang,1 and Xu Zhang1
1Institute of Neuroscience and State Key Laboratory of Neuroscience, 2Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and 3National Engineering Center for Biochip at Shanghai, Shanghai 201203, China
B-type natriuretic peptide (BNP) has been known to be secreted from cardiac myocytes and activate its receptor, natriuretic peptide receptor-A (NPR-A), to reduce ventricular fibrosis. However, the function of BNP/NPR-A pathway in the somatic sensory system has been unknown. In the present study, we report a novel function of BNP in pain modulation. Using microarray and immunoblot analyses, we found that BNP and NPR-A were expressed in the dorsal root ganglion (DRG) of rats and upregulated after intraplantar injection of complete Freund's adjuvant (CFA). Immunohistochemistry showed that BNP was expressed in calcitonin gene-related peptide (CGRP)-containing small neurons and IB4 (isolectin B4)-positive neurons, whereas NPR-A was present in CGRP-containing neurons. Application of BNP reduced the firing frequency of small DRG neurons in the presence of glutamate through opening large-conductance Ca2+-activated K+ channels (BKCa channels). Furthermore, intrathecal injection of BNP yielded inhibitory effects on formalin-induced flinching behavior and CFA-induced thermal hyperalgesia in rats. Blockade of BNP signaling by BNP antibodies or cGMP-dependent protein kinase (PKG) inhibitor KT5823 [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester] impaired the recovery from CFA-induced thermal hyperalgesia. Thus, BNP negatively regulates nociceptive transmission through presynaptic receptor NPR-A, and activation of the BNP/NPR-A/PKG/BKCa channel pathway in nociceptive afferent neurons could be a potential strategy for inflammatory pain therapy.
