Optically recorded response of the superficial dorsal horn: dissociation from neuronal activity, sensitivity to formalin-evoked skin nociceptor activation.

Optically recorded response of the superficial dorsal horn: dissociation from neuronal activity, sensitivity to formalin-evoked skin nociceptor activation.
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DOI:
10.1152/jn.00976.2004
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发表时间:
2005-07
影响因子:
2.5
通讯作者:
Jaekwang Lee;M. Tommerdahl;O. Favorov;B. Whitsel
Jaekwang Lee;M. Tommerdahl;O. Favorov;B. Whitsel
中科院分区:
医学3区
文献类型:
--
作者:
Jaekwang Lee;M. Tommerdahl;O. Favorov;B. Whitsel

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在大鼠脊髓中,以激活C-纤维的强度对背根进行切片重复电刺激引起同侧背角(DH(s))的浅表部分中的透光率(OIS(DR))的缓慢发展和延长(30-50 s)的变化。抑制星形胶质细胞代谢[通过浴用400 μ M氟乙酸和200 μ M谷氨酰胺(FAc + Gln)]或干扰神经胶质细胞和神经元K+转运[通过100 μ M 4-氨基吡啶(4-AP)]导致OIS(DR)和突触后DH(s)对单脉冲恒流背根刺激(P-PSP(DR))的反应解离。FAc+Gln组OIS(DR)降低,P-PSP(DR)不变; 4-AP组P-PSP(DR)升高,OIS(DR)降低。相反,当K(+)o升高至8 mM时,OIS(DR)和P-PSP(DR)均增加。这些来自正常受试者切片的观察结果被解释为表明OIS(DR)主要反映与DH(s)星形胶质细胞摄取K+和谷氨酸(GLU)相关的细胞体积和光散射变化。在3-5天前接受福尔马林皮内注射的受试者的切片中,OIS(DR)和注射部位同侧DH(s)对15 mM K+或100 μ M GLU的100-ms局部应用(通过吹式移液管)的反应均显著降低,DH(s)对升高的K(+)o的正常灵敏度降低。综合考虑,这些观察结果提出了一种可能性,即DH(s)K(+)o和GLU(o)的调节受损可能导致皮内注射福尔马林后CNS疼痛回路的启动和维持以及感觉运动异常。
In rat spinal cord, slice repetitive electrical stimulation of the dorsal root at an intensity that activates C-fibers evokes a slow-to-develop and prolonged (30-50 s) change in light transmittance (OIS(DR)) in the superficial part of the ipsilateral dorsal horn (DH(s)). Inhibition of astrocyte metabolism [by bath-applied 400 microM fluoroacetate and 200 microM glutamine (FAc + Gln)] or interference with glial and neuronal K+ transport [by 100 microM 4-aminopyridine (4-AP)] leads to dissociation of the OIS(DR) and the postsynaptic DH(s) response to a single-pulse, constant-current dorsal root stimulus (P-PSP(DR)). The OIS(DR) decreases under FAc+Gln, whereas the P-PSP(DR) remains unaltered; under 4-AP, the P-PSP(DR) increases, but the OIS(DR) decreases. In contrast, both the OIS(DR) and P-PSP(DR) increase when K(+)o is elevated to 8 mM. These observations from slices from normal subjects are interpreted to indicate that the OIS(DR) mainly reflects cell volume and light scattering changes associated with DH(s) astrocyte uptake of K+ and glutamate (GLU). In slices from subjects that received an intracutaneous injection of formalin 3-5 days earlier, both the OIS(DR) and the response of the DH(s) ipsilateral to the injection site to 100-ms local application (via puffer pipette) of 15 mM K+ or 100 microM GLU were profoundly reduced, and the normally exquisite sensitivity of the DH(s) to elevated K(+)o is decreased. Considered collectively, the observations raise the possibility that impaired regulation of DH(s) K(+)o and GLU(o) may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities that develop following intracutaneous formalin injection.