Nakatsuka Terumasa, Park Jin-Soo, Kumamoto Eiichi, Tamaki Tetsuya, Yoshimura Megumu
Department of Physiology, Saga Medical School, Nabeshima, Saga 849-8501, Japan Department of Orthopedic Surgery, Wakayama Medical School, Wakayama 640-8516, Japan.
Pain. 1999 Jul;82(1):39-47. doi: 10.1016/S0304-3959(99)00037-8.
Although hyperalgesia elicited by inflammation has been shown to be partly due to central sensitization, the cellular mechanisms are not clear at the moment. The present study was designed to address this issue using the blind whole-cell patch-clamp technique; glutamatergic primary-afferent inputs to substantia gelatinosa (SG) neurons were compared between spinal cord slices of naive rats and rats inflamed by an intraplantar injection of complete Freund's adjuvant. In naive rats, a large number of SG neurons examined received monosynaptic A delta- (69% of 41 neurons innervated by A fibers) and/or polysynaptic C- (94% of 36 neurons innervated by C fibers) afferent inputs, and only a few neurons received monosynaptic A beta inputs (7%). In addition, when examined in neurons which have both of the A- and C-afferent inputs, A afferent-evoked excitatory postsynaptic currents (EPSCs) were larger in amplitude than C afferent-induced ones; a ratio (A/C ratio) of the former to latter amplitude was 1.8 +/- 0.1 (n = 36). In inflamed rats, a change in the synaptic responses was observed: (1) SG neurons receiving monosynaptic A delta-afferent inputs decreased in number (to 20% of 30 neurons tested, innervated by A fibers), whereas those having monosynaptic A beta-afferent inputs increased to 33%, and (2) the A/C ratio decreased to 0.7 +/- 0.1 (n = 33). These results suggest that after inflammation, a substantial number of A beta-afferents sprout into the SG from their original location (laminae III-V) and that sensory information that used to be conveyed directly to the SG through A delta afferents is transmitted there indirectly through interneurons. These reorganizations of sensory pathway may contribute, at least in part, to underlying mechanisms for the development of hyperalgesia due to inflammation.
尽管炎症引起的痛觉过敏已被证明部分归因于中枢敏化，但其细胞机制目前尚不清楚。本研究旨在使用盲法全细胞膜片钳技术解决这一问题；比较了正常大鼠和足底注射完全弗氏佐剂致炎大鼠脊髓切片中，向脊髓背角胶状质（SG）神经元的谷氨酸能初级传入输入。在正常大鼠中，大量被检测的SG神经元接受单突触Aδ-（由A纤维支配的41个神经元中的69%）和/或多突触C-（由C纤维支配的36个神经元中的94%）传入输入，只有少数神经元接受单突触Aβ输入（7%）。此外，在同时具有A-和C-传入输入的神经元中进行检测时，A传入诱发的兴奋性突触后电流（EPSCs）的幅度大于C传入诱发的电流；前者与后者幅度的比值（A/C比值）为1.8±0.1（n = 36）。在致炎大鼠中，观察到突触反应的变化：（1）接受单突触Aδ传入输入的SG神经元数量减少（降至由A纤维支配的30个测试神经元的20%），而具有单突触Aβ传入输入的神经元增加到33%，以及（2）A/C比值降至0.7±0.1（n = 33）。这些结果表明，炎症后，大量Aβ传入纤维从其原始位置（Ⅲ-Ⅴ层）向SG发芽，并且过去通过Aδ传入纤维直接传递到SG的感觉信息现在通过中间神经元间接传递到那里。这些感觉通路的重组可能至少部分地促成了炎症引起的痛觉过敏发生的潜在机制。
