Heat hypersensitivity is attenuated with altered expression level of spinal astrocytes after sciatic nerve injury in TRPV1 knockout mice
Heat hypersensitivity is attenuated with altered expression level of spinal astrocytes after sciatic nerve injury in TRPV1 knockout mice
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DOI：
10.1016/j.neures.2020.12.007
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发表时间：
2021-07-31
影响因子：
2.9
通讯作者：
Sakai, Akinori
中科院分区：
文献类型：
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作者：
Baba, Kazuhiko;Kawasaki, Makoto;Sakai, Akinori
瞬时受体电位香草素1(TRPV1)调节疼痛。研究表明，在神经病理性疼痛模型中，TRPV1在脊髓背角表达上调，但其机制尚不清楚。在这里，我们通过采用部分坐骨神经结扎(PSNL)的方法，在成年雄性C57BL/6J(野生型：WT)和TRPV1基因敲除(TRPV1-/-)小鼠上研究了TRPV1调节神经病理性疼痛的机制。我们分析了L5同侧脊髓背角I、II层的机械/热敏感性(von Frey试验/热板法)和神经胶质细胞/神经元活性(免疫荧光法Iba1/GFAP/FosB)。PSNL组第7天和第14天的机械/热敏感性、小胶质细胞Iba-1和星形胶质细胞GFAP的表达水平以及FosB阳性神经元的数量均显著高于WT和TRPV1-/-小鼠的假手术组和非手术组。虽然机械敏感性在WT和TRPV1-/-小鼠之间相当，但在PSNL后第14天，TRPV1-/-小鼠对热敏感的阈值显著高于WT小鼠。相反，在PSNL后第7天和第14天，TRPV1/-小鼠的FosB阳性神经元的增加明显低于WT小鼠。这些结果提示，TRPV1可能通过增加脊髓背角星形胶质细胞来调节热感觉。(C)2021年爱思唯尔公司和日本神经科学学会。版权所有。
Transient receptor potential vanilloid 1 (TRPV1) modulates pain. Studies have indicated that TRPV1 is upregulated in the spinal dorsal horn in the neuropathic pain model, but its mechanism is unknown. Here, we examined the mechanism by which TRPV1 modulates neuropathic pain by employing partial sciatic nerve ligation (pSNL) in adult male C57BL/6 J (wild-type: WT) and TRPV1 knockout (Trpv1-/-) mice. We analyzed mechanical/heat sensitivities (von Frey test/hot plate test) and glial/neuronal activities (Iba1/GFAP/FosB by immunofluorescence) in laminae I and II in the L5 ipsilateral dorsal horn of the spinal cord. Mechanical/heat sensitivities, expression levels of microglial Iba-1 and astrocytic GFAP, and the number of FosB-positive neurons were significantly increased on days 7 and 14 in the pSNL group compared with the sham-operated and non-operated groups of both WT and Trpv1-/-mice. While mechanical sensitivity was comparable between WT and Trpv1-/-mice, the threshold against heat sensitivity was markedly prolonged in Trpv1-/-than WT mice on day 14 after pSNL. Conversely, the increment of FosB positive neurons was significantly attenuated in Trpv1-/-than WT mice on days 7 and 14 after pSNL. These results suggest that TRPV1 may modulate thermal perception via increased astrocytes in the dorsal horn of the spinal cord. (c) 2021 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.