奥曲肽对福尔马林诱导的大鼠痛反应和脊髓背角pCREB表达的抑制作用

Inhibitory action of octreotide on the nociceptive responses and espression of pCREB in the spinal dorsal horn of rat with formalin- induced pain

目的:本研究旨在观察局部应用奥曲肽对福尔马林诱发的痛反应以及脊髓背角磷酸化的c AMP反应元件结合蛋白(phosphorylated c AMP response element binding protein,p CREB)表达的影响。方法:实验采用行为学观察和外周神经单纤维记录的方法,研究足底注射2.5%福尔马林50μl诱发的SD大鼠痛反应;同时采用免疫组织化学染色观察脊髓背角p CREB的表达。结果:福尔马林足底注射可以引起大鼠典型的双相性痛行为,敏化C和Aδ类初级传入单位,包括机械阈值的下降和传入放电率的增加(P<0.001);同时福尔马林注射还可以明显增加双侧脊髓背角p CREB的表达,以注射侧最为显著(P<0.05和P<0.01)。足底注射生长抑素类似物奥曲肽(20μmol/L,50μl)可明显降低福尔马林诱发的第二相特异性伤害行为评分,减少C和Aδ类单位的传入放电率;同时局部应用奥曲肽还可以部分抑制福尔马林诱发的脊髓背角p CREB表达增加。结论:结果提示,局部应用奥曲肽可以显著抑制福尔马林诱发的痛反应,脊髓背角p CREB参与了此过程。

Objective： The purpose of the present study was to observe the effect of local application of octreotide on the nociceptive responses induced by formalin and expression of phosphorylated cAMP response element binding protein （pCREB） in the spinal dorsal horn. Methods： The behavioral observation and recording on single unit from peripheral nerve were used to investigate the nociceptive responses induced by intra-plantar injection of formalin （2.5%, 50 μl） in Sprague Dawley （SD） rats, and immunohistochemical method was used to observe the expression of pCREB positive cells in the spinal dorsal horn. Results： The intra-plantar injection of formalin induced typical biphasic nociceptive behaviors and sensitized the C and A~ units of primary sensory nerve including the decrease in mechanical threshold and the in- crease of discharge rates （P 〈 0. 001 ）. Meanwhile, the expression of pCREB increased in both sides of spinal dorsal horn, especially in ipsilateral side after formalin injection （P 〈 0.05 and P 〈0.01 ）. Intra-plantar injection of octreotide （20 txmol/L, 50 μl） , an analogue of somatostatin, significantly inhibited the second phase of composite pain score for specific nociceptive behaviors and decreased the discharge rates of C and A~ units induced by formalin. Meanwhile, local application of octreotide partly inhibited the increase in expression of pCREB in dorsal horn induced by formalin. Conclu- sion ： These results suggested that local application of octreotide significantly inhibited the nociceptive responses induced by formalin, and pCREB in spinal cord might be involved in this process.