Onda Akira, Murata Yasuaki, Rydevik Björn, Larsson Karin, Kikuchi Shinichi, Olmarker Kjell
Department of Orthopaedics, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.
Spine (Phila Pa 1976). 2004 Sep 1;29(17):1857-61. doi: 10.1097/01.brs.0000137054.08788.b2.
The effect of infliximab, a chimeric monoclonal antibody to TNF-alpha, on induction of brain-derived neurotrophic factor (BDNF) was examined using an experimental herniated nucleus pulposus (NP) model.
To investigate whether treatment of infliximab could attenuate an induction of BDNF, which functions as a modulator of pain, following NP application to the nerve root.
Evidence from basic scientific studies proposes that TNF-alpha is involved in the development of NP-induced nerve injuries. However, the therapeutic mechanisms of infliximab against pain have not been elucidated experimentally.
Twenty rats were used in this study. In the test groups, the animals underwent application of NP to the L4 nerve roots and received a single systemic (intraperitoneal) injection of infliximab at the time of surgery (Infli-0 group, n = 5) or at 1 day after operation (Infli-1 group, n = 5). As a control treatment, sterile water was administered intraperitoneally to 5 rats with NP application (NP group) and to 5 sham-operated rats (sham group). On day 3 after surgery, the L4 dorsal root ganglion (DRG) and L4 spinal segment were harvested and assessed regarding BDNF immunoreactivity. RESULTS.: Application of NP induced a marked increase of BDNF immunoreactivity in number in the DRG neurons and within the superficial layer in the dorsal horn compared with the sham group (P < 0.01). Infliximab treatment in the Infli-0 and Infli-1 groups reduced the BDNF induction in both DRG and spinal cord (P < 0.05).
These findings indicate that infliximab attenuates the elevated BDNF levels induced by NP. The present study therefore further indicates the importance of TNF-alpha in sciatica due to disc herniation and the possible therapeutic use of a TNF-alpha inhibitor for this condition.
使用实验性椎间盘突出症模型，研究抗TNF-α嵌合单克隆抗体英夫利昔单抗对脑源性神经营养因子（BDNF）诱导作用的影响。
研究英夫利昔单抗治疗能否减轻神经根应用椎间盘组织后作为疼痛调节因子的BDNF的诱导作用。
基础科学研究的证据表明，TNF-α参与了椎间盘突出症所致神经损伤的发生。然而，英夫利昔单抗治疗疼痛的机制尚未通过实验阐明。
本研究使用20只大鼠。在试验组中，动物接受L4神经根应用椎间盘组织，并在手术时（英夫利昔单抗0组，n = 5）或术后1天（英夫利昔单抗1组，n = 5）接受单次全身（腹腔内）注射英夫利昔单抗。作为对照治疗，对5只应用椎间盘组织的大鼠（椎间盘组）和5只假手术大鼠（假手术组）腹腔内注射无菌水。术后第3天，采集L4背根神经节（DRG）和L4脊髓节段，评估BDNF免疫反应性。结果：与假手术组相比，应用椎间盘组织诱导DRG神经元和背角浅层内BDNF免疫反应性数量显著增加（P < 0.01）。英夫利昔单抗0组和英夫利昔单抗1组的治疗降低了DRG和脊髓中BDNF的诱导水平（P < 0.05）。
这些发现表明英夫利昔单抗可减轻椎间盘组织诱导的BDNF水平升高。因此，本研究进一步表明TNF-α在椎间盘突出症所致坐骨神经痛中的重要性以及TNF-α抑制剂对这种情况可能的治疗用途。
