Shoda Emi, Kitagawa Junichi, Suzuki Ikuko, Nitta-Kubota Ieko, Miyamoto Makiko, Tsuboi Yoshiyuki, Kondo Masahiro, Masuda Yuji, Oi Yoshiyuki, Ren Ke, Iwata Koichi
Department of Anesthesiology, Nihon University School of Dentistry, Tokyo, Japan.
J Pain. 2009 Jun;10(6):573-85. doi: 10.1016/j.jpain.2008.11.013. Epub 2009 Apr 23.
Although propofol (PRO) is widely used in clinic as a hypnotic agent, the underlying mechanisms of its action on pain pathways is still unknown. Sprague-Dawley rats were assigned to receive PRO or pentobarbital (PEN) and were divided into 2 groups as LIGHT and DEEP hypnotic levels based on the EEG analysis. Rats in each hypnotic level received capsaicin injection into the face and phosphorylated extracellular signal-regulated kinase (pERK) immunohistochemistry was performed in subnucleus caudalis (Vc) and upper cervical spinal cord. In the rats with PEN or PRO administration, a large number of pERK-like immunoreactive (LI) cells was observed in the trigeminal spinal subnuclei interpolaris and caudalis transition zone (Vi/Vc), middle Vc, and transition zone between Vc and upper cervical spinal cord (Vc/C2) following capsaicin injection into the whisker-pad region. The number of pERK-LI cells in Vi/Vc, middle Vc, and Vc/C2 was significantly larger in rats with PRO infusion than those with PEN infusion. The number of pERK-LI cells was increased following an increase in the dose of PRO but not in PEN. The pERK-LI cells were mainly distributed in the Vi/Vc, middle Vc, and Vc/C2 after the bolus infusion of PRO. The expression of pERK-LI cells was depressed after the intravenous lidocaine application before bolus PRO infusion. The present findings suggest that PRO induced an enhancement of the activity of trigeminal nociceptive pathways through nociceptors innervating the venous structure, as indicated by a lidocaine-sensitive increase in pERK. This may explain deep pain around the injection regions during intravenous bolus infusion of PRO.
The effect of propofol administration on ERK phosphorylation in the subregions of the spinal trigeminal complex and upper cervical spinal cord neurons were precisely analyzed in rats with PRO infusion. A large number of pERK-LI cells was observed following intravenous PRO administration, suggesting an enhancement of trigeminal nociceptive activity and that PRO may produce pain through nociceptors innervating the venous structures during infusion.
尽管丙泊酚（PRO）作为一种催眠剂在临床上广泛应用，但其作用于疼痛通路的潜在机制仍不清楚。将Sprague-Dawley大鼠分为接受PRO或戊巴比妥（PEN）组，并根据脑电图分析分为浅催眠水平和深催眠水平2组。每个催眠水平的大鼠均接受辣椒素注射到面部，并在三叉神经脊束核尾侧亚核（Vc）和颈上段脊髓进行磷酸化细胞外信号调节激酶（pERK）免疫组化。在给予PEN或PRO的大鼠中，向须垫区域注射辣椒素后，在三叉神经脊束核极间亚核和尾侧过渡区（Vi/Vc）、Vc中部以及Vc与颈上段脊髓之间的过渡区（Vc/C2）观察到大量pERK样免疫反应性（LI）细胞。输注PRO的大鼠在Vi/Vc、Vc中部和Vc/C2中的pERK-LI细胞数量明显多于输注PEN的大鼠。pERK-LI细胞数量随PRO剂量增加而增加，但PEN则不然。单次推注PRO后，pERK-LI细胞主要分布在Vi/Vc、Vc中部和Vc/C2。在推注PRO前静脉注射利多卡因后，pERK-LI细胞的表达受到抑制。目前的研究结果表明，PRO通过支配静脉结构的伤害感受器诱导三叉神经伤害性通路活性增强，这表现为pERK对利多卡因敏感的增加。这可能解释了静脉推注PRO期间注射区域周围的深部疼痛。
在输注PRO的大鼠中精确分析了丙泊酚给药对脊髓三叉神经复合体亚区和颈上段脊髓神经元中ERK磷酸化的影响。静脉注射PRO后观察到大量pERK-LI细胞，提示三叉神经伤害性活动增强，并且PRO可能在输注期间通过支配静脉结构的伤害感受器产生疼痛。
