8月11日,，中國(guó)科學(xué)院上海生命科學(xué)研究院神經(jīng)科學(xué)研究所的博士研究生張方雄及合作者在張旭研究員指導(dǎo)下完成的研究成果得以發(fā)表。此項(xiàng)成果主要是激活傷害性感覺神經(jīng)元中B型鈉尿肽/鈉尿肽受體A信號(hào)通路抑制炎性痛,。
背根節(jié)中的傷害性感覺神經(jīng)元是痛覺傳導(dǎo)通路的第一站，傷害性刺激使這些神經(jīng)元的傳入纖維釋放谷氨酸等興奮性神經(jīng)遞質(zhì),，向脊髓及大腦傳遞痛覺信息,。張旭研究組首先發(fā)現(xiàn)外周組織炎癥可以顯著增加傷害性感覺神經(jīng)元中B型鈉尿肽及其受體鈉尿肽受體A的基因表達(dá)，隨后他們觀察到在谷氨酸作用條件下,，B型鈉尿肽通過增加大電導(dǎo)鈣激活性鉀離子通道的開放概率來降低傷害性感覺神經(jīng)元的興奮性,，對(duì)痛覺信息傳入起抑制作用。在脊髓腔內(nèi)注射B型鈉尿肽可顯著地抑制急性和慢性炎癥痛,。
因此，由傷害性感覺傳入纖維分泌的B型鈉尿肽通過激活位于突觸前的鈉尿肽受體A對(duì)興奮性突觸傳遞起抑制性調(diào)節(jié)作用,，該研究還提示激活傷害性感覺神經(jīng)元中的B型鈉尿肽/鈉尿肽受體A信號(hào)轉(zhuǎn)導(dǎo)通路有可能是一種新的鎮(zhèn)痛策略,。
該工作得到了科學(xué)院、科技部和國(guó)家自然科學(xué)基金的資助,。（生物谷Bioon.com）
揭密疼痛的感覺與機(jī)理
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Psychological Science：思念愛人可緩解疼痛
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生物谷推薦原文出處：
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.
