Characterization of pain-related behaviors in a rat model of acute-to-chronic low back pain: single vs. multi-level disc injury

M. Barbe, Frank Liu Chen, Regina H. Loomis, M. Harris, Brandon M. Kim, Kevin Xie, Brendan A. Hilliard, Elizabeth R. McGonagle, Taylor D. Bailey, Ryan P. Gares, Megan Van Der Bas, Betsy A. Kalicharan, Lewis Holt-Bright, Laura S. Stone, Paul W Hodges, D. Klyne
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Abstract

Low back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain.Twenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery.DP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure).Thus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles.
急性至慢性腰痛大鼠模型中与疼痛有关的行为特征:单层椎间盘损伤与多层椎间盘损伤
腰痛是最常见的慢性疼痛类型。我们研究了一只或两只腰椎间盘(IVD)受伤的大鼠在18周内与疼痛相关的行为,以确定多层次椎间盘损伤是否会增强/延长疼痛:8只大鼠接受了一个腰椎间盘穿刺术(DP)(L5/6,DP-1);8只大鼠接受了两个腰椎间盘穿刺术(L4/5和L5/6,DP-2);8只大鼠接受了假手术。DP-2大鼠在伤后6周和12周表现出对压力的局部(腰部)敏感性,在伤后12周和18周表现出对压力(大腿上部)的远端敏感性,在伤后6周、12周和18周表现出对触觉(后爪)的远端敏感性。与 Sham DP 大鼠相比,DP-1 大鼠仅在 12 周时表现出局部和远程压力敏感性(没有触觉敏感性)。与受伤前相比,DP 两组大鼠在多周步态测试中的行走距离都有所减少;只有 DP-2 组大鼠在 12 周时的行走距离相对于 Sham DP 组大鼠有所减少。DP-2 组大鼠在 3 周时与一只新的成年雌性大鼠的积极互动减少,从 6 周起在步态测试中表现出犹豫和凝滞。研究结束时(18 周),放射学和组织学分析显示,椎间盘高度降低,穿孔的 IVD 退化。与Sham DP大鼠相比,DP-2大鼠在18周时的血清BDNF和TNFα水平较高,其水平与后爪(触觉)和大腿(压力)的远端敏感性呈正相关。BDNF和TNFα可能起到了促进作用。
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