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The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach.
Journal of Translational Medicine ( IF 7.4 ) Pub Date : 2020-01-17 , DOI: 10.1186/s12967-019-02200-2
Daniela C Rosenberger 1 , Uta Binzen 1, 2 , Rolf-Detlef Treede 1 , Wolfgang Greffrath 1
Affiliation  

BACKGROUND Pain is the vital sense preventing tissue damage by harmful noxious stimuli. The capsaicin receptor TRPV1 is activated by noxious temperatures, however, acute heat pain is only marginally affected in mice after TRPV1 knockout but completely eliminated in mice lacking TRPV1 positive fibers. Exploring contribution of candidate signal transduction mechanisms to heat pain in humans needs translational models. METHODS We used focused, non-damaging, short near-infrared laser heat stimuli (wavelength 1470/1475 nm) to study the involvement of TRPV1-expressing nerve fibers in the encoding of heat pain intensity. Human psychophysics (both sexes) were compared to calcium transients in native rat DRG neurons and heterologously expressing HEK293 cells. RESULTS Heating of dermal and epidermal nerve fibers in humans with laser stimuli of ≥ 2.5 mJ (≥ 25 ms, 100 mW) induced pain that increased linearly as a function of stimulus intensity in double logarithmic space across two orders of magnitude and was completely abolished by desensitization using topical capsaicin. In DRG neurons and TRPV1-expressing HEK cells, heat sensitivity was restricted to capsaicin sensitive cells. Strength duration curves (2-10 ms range) and thresholds (DRGs 0.56 mJ, HEK cells 0.52 mJ) were nearly identical. Tachyphylaxis upon repetitive stimulation occurred in HEK cells (54%), DRGs (59%), and humans (25%). CONCLUSION TRPV1-expressing nociceptors encode transient non-damaging heat pain in humans, thermal gating of TRPV1 is similar in HEK cells and DRG neurons, and TRPV1 tachyphylaxis is an important modulator of heat pain sensitivity. These findings suggest that TRPV1 expressed in dermal and epidermal populations of nociceptors serves as first line defense against heat injury.

中文翻译:

辣椒素受体TRPV1是防止急性非破坏性热量的第一道防线:一种翻译方法。

背景技术疼痛是防止有害有害刺激对组织造成损害的重要感觉。辣椒素受体TRPV1被有害温度激活,但是急性热痛仅在敲除TRPV1后在小鼠中受到轻微影响,而在缺乏TRPV1阳性纤维的小鼠中则完全消除。探索候选信号转导机制对人类热痛的贡献需要转化模型。方法我们使用聚焦的,无损的,短的近红外激光热刺激(波长1470/1475 nm)来研究表达TRPV1的神经纤维在热痛强度编码中的作用。将人类心理物理学(男女)与天然大鼠DRG神经元和异源表达HEK293细胞的钙瞬变进行了比较。结果激光刺激≥2的人的真皮和表皮神经纤维发热。5 mJ(≥25 ms,100 mW)引起的疼痛随着双对数空间中两个数量级的刺激强度而线性增加,并通过局部使用辣椒素脱敏而完全消除。在DRG神经元和表达TRPV1的HEK细胞中,热敏感性仅限于辣椒素敏感性细胞。强度持续时间曲线(2-10 ms范围)和阈值(DRG 0.56 mJ,HEK细胞0.52 mJ)几乎相同。重复刺激后的速激肽发生在HEK细胞(54%),DRG(59%)和人类(25%)中。结论表达TRPV1的伤害感受器编码人类短暂的非破坏性热痛,HEPV细胞和DRG神经元中TRPV1的热门控相似,TRPV1速激肽是热痛敏感性的重要调节剂。
更新日期:2020-01-17
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