Institute of Neurosciences, Institute of Neuroscience, Brain Science and Intelligent Technology Innovation Center, Academician Zhang Xu, a research group in the latest study revealed nociceptive heat stimulation of the key to the regulation of pain, the relevant research results online recently published in the internationally renowned academic journal " Neurons". It is reported that the paper will be published in the form of cover paper.
Nociceptive temperature (overheating and undercooling), mechanical and chemical stimuli can cause pain and avoid response, thereby protecting the body is no longer hurt. For a long time, the neuroscientists widely believe that the conduction of thermal pain signal and transient receptor potential cation channel V1 (TRPV1) and other temperature receptors, but experimental results show that these temperature receptors are only partially involved in heat conduction pain, suggesting that there may be unknown Heat conduction and regulation mechanism.
This study found that fibroblast growth factor 13 (FGF13) is a key regulator of thermal pain, and revealed that FGF13 is a novel molecular cellular mechanism responsible for the regulation of voltage-gated sodium channel Nav1.7. Zhang Xu group of single-cell transcriptome and in vivo electrophysiological recording technique, the dorsal root ganglion somatic sensory neurons are divided into 10 types, including 6 major types of nociceptive mechanical and thermal sensory neurons, and observed in the FGF13 is selectively expressed in various types of nociceptive mechanical and thermal sensory neurons in the adult mouse nervous system, and is low in other neural tissues and neurons. The team prepared mice that specifically knocked down the FGF13 gene in dorsal root ganglionic nociceptive sensory neurons and found that these FGF13-deficient mice selectively lost complete response to nociceptive thermal stimuli (greater than 43 ° C) Nociceptive mechanical stimulation and other senses to maintain normal. Functional magnetic resonance imaging (fMRI) revealed that the loss of nociceptive sensory neurons (FGF13) led to a significant reduction in the brain's response to nociceptive thermal stimuli, and identified brain regions associated with thermal pain perception, memory, and mood. The researchers also found that FGF13 and Nav1.7 interaction, increased Nav1.7 current. Nociceptive heat stimulation increased the interaction of FGF13 and Nav1.7, thus maintaining the amount of Nav1.7 on the cell membrane. The neurons produce persistent action potentials under the nociceptive heat stimulation and transmit pain information to the central nervous system. The study further found that the binding site of FGF13 and Nav1.7 at the carboxy terminus of Nav1.7, blocking FGF13 and Nav1.7 binding can also reduce the heat pain. Thus, FGF13 can modulate thermal pain by acting on Nav1.7.
The findings not only show that FGF13, which is expressed in nociceptive mechanical and thermal sensory neurons, selectively regulates heat pain and that FGF13 acts on Nav1.7 as a key mechanism of heat-pain transmission, breaking through the current pain theory Conceptual understanding, and provides a new analgesic target molecules.
It is reported that this work is completed by assistant researcher Yang Liu, postdoctoral fellow Dong Fei and research team under the guidance of researcher Zhang Xu, Shanghai Institute of Clinical Research, Chinese Academy of Sciences Yang Qing, Chen Limin and Xu Fuqiang (Wuhan Institute of Physical Mathematics, Chinese Academy of Sciences) (Beijing Institute of Biochemistry and Cell Biology) and Cheng Xiaoyang, associate professor (Shanghai Jiaotong University School of Medicine) were involved in the study of cell biology and electrophysiology. This work was funded by the Chinese Academy of Sciences Strategic Leadership Program (B), the National Natural Science Foundation of China and the Shanghai Science and Technology Project.
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