Fibroblast growth factor 13 actes on sodium channel 1.7 to regulate thermal pain

On February 2, neurons, an international academic journal, published a research paper online entitled "Fibroblast growth factor 13 acting on sodium channel 1.7 to regulate thermal pain", which will then be published in print as a cover paper.
the study revealed the key regulatory mechanisms for pain caused by injury-causing heat stimulation, which was completed by Zhang Xu Research Group of the Institute of Neuroscience of the Shanghai Institute of Life Sciences of the Chinese Academy of Sciences and the Center for Excellence and Innovation in Brain Science and Intelligent Technology.
damage-causing stimulation temperature (overheating and over-cooling), mechanical and chemical stimuli can cause pain and evade reactions, thus protecting the body from harm.
of different properties are converted into action-level signals through specific membrane proteins, which travel along the sensory nerve into the spine to the brain.
For a long time, the neuroscience community has widely believed that the conduction of thermal pain signals is related to temperature receptors such as instantaneous receptor potential cation channel V1 (TRPV1), but experimental results show that these temperature receptors are only partially involved in thermal pain conduction, suggesting that there may be unknown mechanisms for heat pain transmission and regulation.
the study found that fibroblast growth factor 13 (FGF13) is the key regulatory molecule of thermal pain, revealing that FGF13's regulation of voltage-gated sodium channel Nav1.7 is a new molecular cell biological mechanism of thermal pain.
Zhang Xu's team recently used single-cell transcription groups and in-body electrophysiological recording techniques to divide the back root somatic sensory neurons into 10 types, including 6 major types of damaged mechanical and thermal sensory neurons (Li et al., Cell Research, 2016).
raises new scientific questions about whether these different types of damaged machinery have the same thermal pain regulation mechanisms as thermal sensory neurons.
they observed that FGF13 was selectively expressed in a variety of damaged mechanical and thermal sensory neurons (Figure A) in the nervous system of adult mice, with lower levels of expression in other nerve tissues and neurons.
team prepared mice that specifically knocked out the FGF13 gene in the back root injury sensory neurons and found that the mice that were missing FGF13 selectively lost their response to injury-like thermal stimuli (greater than 43oC) (Figure B) and remained normal for damaged mechanical stimuli.
functional magnetic resonance imaging (fMRI) reveals that the absence of injuric sensory neurons FGF13 has led to a significant decline in the brain's response to injury-causing thermal stimuli (Figure C), identifying brain regions associated with heat pain perception, memory and mood.
also found that FGF13 and Nav1.7 interacted to increase Nav1.7 currents.
injury thermal stimulation increases the interaction between FGF13 and Nav1.7, thus maintaining the number of Nav1.7 on the cell membrane, causing neurons to produce persistent motion levels under injury thermal stimulation and transmitting pain information to the central nervous system (Figure D).
they further found that the binding points of FGF13 and Nav1.7 were at the base of Nav1.7, and that blocking the binding of FGF13 to Nav1.7 also reduced heat pain.
, FGF13 can regulate thermal pain by acting on Nav1.7.
In this study, Zhang Xu's team found that FGF13, expressed in injury machinery and thermal sensory neurons, selectively regulates thermal pain, and reveals that FGF13's role in Nav1.7 is the key mechanism of thermal pain conduction, breaking through the conceptual understanding of the current theory of pain and providing new analgesic target molecules.
The work was carried out by assistant researcher Yang Liu, postdoctoral researcher Dong Fei and research team under the guidance of researcher Zhang Xu, postdoctoral researcher Yang Qing of the Shanghai Clinical Research Center of the Chinese Academy of Sciences under the guidance of researchers Chen Limin and Xu Fuqiang (Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences) to complete mouse brain imaging research, Shanghai Academy of Biological Sciences Institute of Biochemistry and Cell Biology researcher Bao Wei and Shanghai Jiaodian University School of Medicine associate researcher Cheng Xiaoyang to guide cell biology and electrophysiology research.
the work was supported by the Chinese Academy of Sciences Strategic Pilot Science and Technology Special (Category B), the National Natural Science Foundation of China and the Shanghai Science and Technology Special Project.
.