Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Mol Pain. 2020 Jan-Dec;16:1744806920903515. doi: 10.1177/1744806920903515.
Somatosensation encompasses a wide range of sensations including pain, itch, touch, and temperature and is essential for the detection of environmental stimuli, ultimately allowing an organism to escape, communicate, and adapt to its environment. Such sensations are detected by primary sensory neurons whose nerve endings are located in the skin. Compared to external stimuli, mechanisms underlying endogenous stimulation of primary sensory neurons, such as by lipids, are still largely unknown. Here, we focus on one of the endogenous bioactive lipids, sphingosine-1-phosphate (S1P), to investigate the physiological roles of S1P in pain and itch. We showed that S1P-induced calcium responses in sensory neurons through S1P receptors. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are nonselective calcium-permeable ion channels that are known to be involved in pain and itch. Neurons that respond to S1P show reduced responsiveness when treated with antagonists that block either TRPA1 or TRPV1 alone or in combination. In addition, using single and double knockout mice (TRPA1; TRPV1; TRPA1/TRPV1) with loss of function of these channels, we demonstrated that both TRP channels are involved in S1P-induced neuronal responses in vitro. Next, we examined the effects of S1P on pain and itch responsiveness in freely behaving mice post-S1P injection into the cheek, neck, and hind paw. Our findings reveal that S1P induces both pain and itch in vivo and that these responses are partially dependent upon the TRPV1, but not TRPA1 channels.
躯体感觉包括广泛的感觉，包括疼痛、瘙痒、触摸和温度，对于环境刺激的检测至关重要，最终使生物体能够逃避、交流和适应其环境。这些感觉是由初级感觉神经元检测到的，其神经末梢位于皮肤中。与外部刺激相比，内源性刺激初级感觉神经元的机制，如脂质，在很大程度上仍然未知。在这里，我们专注于内源性生物活性脂质之一，即鞘氨醇-1-磷酸（S1P），以研究 S1P 在疼痛和瘙痒中的生理作用。我们表明，S1P 通过 S1P 受体在感觉神经元中诱导钙反应。瞬时受体电位阳离子通道亚家族 A 成员 1（TRPA1）和香草素 1（TRPV1）是非选择性钙通透性离子通道，已知它们参与疼痛和瘙痒。对 S1P 有反应的神经元在用单独或联合阻断 TRPA1 或 TRPV1 的拮抗剂处理时，其反应性降低。此外，使用具有这些通道功能丧失的单和双敲除小鼠（TRPA1；TRPV1；TRPA1/TRPV1），我们证明这两种 TRP 通道都参与了 S1P 在体外诱导神经元反应。接下来，我们检查了 S1P 对颊、颈和后爪中 S1P 注射后自由活动小鼠的疼痛和瘙痒反应的影响。我们的发现表明 S1P 在体内诱导疼痛和瘙痒，并且这些反应部分依赖于 TRPV1，但不依赖于 TRPA1 通道。
