Barbe Mary F, Chen Frank Liu, Loomis Regina H, Harris Michele Y, Kim Brandon M, Xie Kevin, Hilliard Brendan A, McGonagle Elizabeth R, Bailey Taylor D, Gares Ryan P, Van Der Bas Megan, Kalicharan Betsy A, Holt-Bright Lewis, Stone Laura S, Hodges Paul W, Klyne David M
Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States.
Medical Doctor Program, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States.
Front Pain Res (Lausanne). 2024 May 6;5:1394017. doi: 10.3389/fpain.2024.1394017. eCollection 2024.
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.
下腰痛是最常见的慢性疼痛类型。我们研究了接受一或两个腰椎间盘（IVD）损伤的大鼠在18周内与疼痛相关的行为，以确定多节段椎间盘损伤是否会加重/延长疼痛。
使用23只成年雌性Sprague-Dawley大鼠：8只接受一个腰椎间盘（L5/6）的椎间盘穿刺（DP）（DP-1组）；8只接受两个腰椎间盘（L4/5和L5/6）的DP（DP-2组）；8只接受假手术。
DP-2组大鼠在损伤后6周和12周表现出局部（下背部）对压力敏感，在12周和18周表现出对压力的远程敏感（大腿上部），在6周、12周和18周表现出对触摸（后爪）敏感。与假手术DP组大鼠相比，DP-1组大鼠仅在12周时表现出局部和远程压力敏感（无触觉敏感）。与损伤前相比，两个DP组在数周的步态测试中行走距离均减少；仅DP-2组大鼠在12周时相对于假手术DP组大鼠行走距离减少。DP-2组大鼠在3周时与新成年雌性大鼠的积极互动减少，从6周起在步态分析中出现犹豫和僵住。在研究结束时（18周），放射学和组织学分析显示穿刺椎间盘的高度降低和退变。与假手术DP组大鼠相比，DP-2组大鼠在18周时血清BDNF和TNFα水平更高，且水平与后爪（触觉）和大腿（压力）的远程敏感呈正相关。
因此，与单节段椎间盘损伤相比，多节段椎间盘损伤导致局部和远程更早、更持久且更严重的不适。BDNF和TNFα可能起作用。
