HSV病毒示踪腰椎间盘突出症模型大鼠中枢敏化的实验研究

Tracing research of central sensitization in lumbar disc herniation rat models through the HSV virus

目的:应用单纯疱疹病毒(HSV)顺行跨突触示踪技术,明确腰椎间盘突出症(LDH)大鼠脊髓和脑区内参与疼痛中枢敏化的相关核团,阐明LDH源性疼痛的中枢敏化机制。方法:通过足底注射HSV病毒,应用免疫荧光染色增强的方法,比较LDH组与假手术组(Sham)大鼠HSV标记阳性神经元在背根神经节、脊髓及脑区的分布情况。结果:HSV病毒在注射7天内可经足底通过坐骨神经(SC)、背根神经节(DRG)及脊髓传递至中枢脑区,主要包括延髓头端腹内侧区(RVM)、蓝斑(LC)、中缝核缘(Rli)、中脑导水管周围灰质(vlPAG)、室旁核(PVN)及初级感觉皮层后肢代表区(S1HL)。LDH大鼠PVN及S1HL中,对侧荧光标记的阳性神经元显著多于同侧。结论:腰椎间盘突出症模型大鼠痛觉传递通路为SC-DRG-DH-(RVM-Rli)/LC-vlPAG-PVN-S1HL,PVN与S1HL是参与腰椎间盘突出症源性疼痛中枢敏化的重要核团。

Objective:The present study was to observe the related central nuclei involved in LDH central sensitization in the spinal cord and brain by herpes simplex virus(HSV)anterograde neuronal tracing technique,to further clarify the mechanism of LDH central sensitization.Methods:The HSV virus was injected into the hindpaw,to compare the distribution of HSV-labeled positive neurons in the dorsal root ganglia,spinal cord and brain regions in the the rats by implantation of autologous nucleus pulposus(NP)harvested from tail with the Sham group by the technology of immunofluorescence staining enhancement.Results:The virus injected into the hindpaw was specifically transported to the brain area that inclouds rostroventromedial medulla(RVM),locus coeruleus(LC),rostral linear nucleus of the raphe(Rli),ventrolateral periaqueductal gray(vlPAG),paraventricular nucleus(PVN)and primary somatosensory cortex of hindlimb(S1HL)within 1 week,through the sciatic nerve,the dorsal root ganglion(DRG)and the dorsal horn(DH)of spinal cord.Compared with Ipsilateral part,the contralateral part of PVN and S1HL in LDH group appeared more infected neurons significantly.Conclusion:The pathway of SC—DRG—DH—(RVM—Rli)/LC—vlPAG—PVN—S1HL may be a main neural circuit of nociceptive transmission of LDH rats.PVN and S1HL may be involved in LDH of pain modulation and pathogenesis.