Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study
Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study
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DOI：
10.22603/ssrr.2018-0110
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发表时间：
2019-04
影响因子：
1.2
通讯作者：
Hiroki Ushirozako;G. Yoshida;D. Togawa;T. Omura;T. Hasegawa;Yu Yamato;T. Banno;H. Arima;Shin Oe;Yuki Mihara;Tomohiro Yamada;Takahiro Natsume;S. Ogawa;Y. Awaga;H. Takamatsu;Y. Matsuyama
中科院分区：
文献类型：
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作者：
Hiroki Ushirozako;G. Yoshida;D. Togawa;T. Omura;T. Hasegawa;Yu Yamato;T. Banno;H. Arima;Shin Oe;Yuki Mihara;Tomohiro Yamada;Takahiro Natsume;S. Ogawa;Y. Awaga;H. Takamatsu;Y. Matsuyama
目前缺乏可翻译的临床前腰痛（LBP）模型。乳脂蛋白酶是一种用于治疗腰椎间盘突出症的蛋白水解酶，可诱导椎间盘源性腰痛。目前的研究建立了非人类灵长类动物椎间盘源性腰痛的行为模型。临床腰痛患者观察到明显的脑激活。因此，目前的研究还试图确定椎间盘源性腰痛猕猴的大脑活动随时间的变化。方法用压力计测量8只成年雄性束状猕猴L4/L5背部压力反应。抽吸L4 ~ L5间IVD髓核，在透视引导下注射乳清蛋白酶（1 mg/mL） （n = 2）。在两只猕猴中，髓核只被抽吸。使用3.0T磁共振成像扫描仪评估4只猕猴在治疗前和治疗后1、3、9和14天对下背部施加压力的大脑激活反应。结果治疗前平均反应压（±SD）为1.4±0.1 kg。乳清蛋白治疗1 d后反应压降至0.6±0.05 kg (P < 0.01)，提示压力超敏。随着时间的推移，乳清蛋白治疗后的血压阈值逐渐恢复正常。仅吸入后，反应压力为1.4±0.05 kg，与未损伤对照组无显著差异。乳清蛋白治疗后第1天和第3天二级体感觉皮层和岛叶皮层出现激活；仅吸吸后无激活。结论髓核酶治疗可引起急性腰痛和疼痛相关脑区压力诱发激活。目前的椎间盘源性腰痛模型与临床腰痛相似，可用于进一步阐明急性腰痛的机制。
Introduction There is currently a lack of translatable, preclinical models of low back pain (LBP). Chymopapain, a proteolytic enzyme used to treat lumbar intervertebral disc (IVD) herniation, could induce discogenic LBP. The current study developed a behavioral model of discogenic LBP in nonhuman primates. Significant brain activation is observed in clinical LBP. Thus, the current study also sought to define brain activation over time in a macaque with discogenic LBP. Methods Responses to pressure applied to the back at L4/L5 were measured in eight adult male Macaca fasciculata using a pressure algometer. The nucleus pulpous of the IVD between L4 and L5 was aspirated and chymopapain (1 mg/mL) was injected under fluoroscopic guidance (n = 2). In two macaques, the nucleus pulpous was only aspirated. Brain activation in response to pressure applied to the lower back was assessed using a 3.0T magnetic resonance imaging scanner in four macaques before and 1, 3, 9, and 14 days after treatment. Results The mean (±SD) response pressure before treatment was 1.4 ± 0.1 kg. One day after chymopapain treatment, the response pressure decreased to 0.6 ± 0.05 kg (P < 0.01), suggestive of pressure hypersensitivity. Over time, the pressure thresholds following chymopapain treatment gradually returned to normal. Following aspiration only, the response pressure was 1.4 ± 0.05 kg, which was not significantly different from the uninjured controls. There was activation of the secondary somatosensory cortex and insular cortex one and three days after chymopapain treatment; there was no activation following aspiration only. Conclusions Enzymatic treatment of the nucleus pulpous leads to acute LBP and pressure-evoked activation in pain-related brain areas. The current model of discogenic LBP parallels clinical LBP and could be used to further elaborate the mechanism of acute LBP.