Inhibiting tumor necrosis factor-alpha at time of induced intervertebral disc injury limits long-term pain and degeneration in a rat model

被引:45
作者
Evashwick-Rogler, Thomas W. [1 ]
Lai, Alon [1 ]
Watanabe, Hironobu [1 ,2 ]
Salandra, Jonathan M. [1 ]
Winkelstein, Beth A. [3 ,4 ]
Cho, Samuel K. [1 ]
Hecht, Andrew C. [1 ]
Iatridis, James C. [1 ]
机构
[1] Icahn Sch Med Mt Sinai, Leni & Peter W May Dept Orthopaed, 1 Gustave Levy Pl,Box 1188, New York, NY 10029 USA
[2] Keiyu Orthoped Hosp, Keiyu Spine Ctr, Tatebayashi, Japan
[3] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA
[4] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
axial back pain; discogenic pain; disc height; infliximab; intervertebral disc degeneration; low back pain; mechanical hyperalgesia; tumor necrosis factor-alpha; LOW-BACK-PAIN; NERVE GROWTH-FACTOR; IN-VIVO MODEL; TNF-ALPHA; ANIMAL-MODELS; CENTRAL SENSITIZATION; ASYMPTOMATIC SUBJECTS; NEEDLE PUNCTURE; SENSORY NEURONS; GLOBAL BURDEN;
D O I
10.1002/jsp2.1014
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
BackgroundPainful intervertebral disc (IVD) degeneration has tremendous societal costs and few effective therapies. Intradiscal tumor necrosis factor-alpha (TNF alpha) is commonly associated with low back pain, but the direct relationship remains unclear. PurposeTreatment strategies for low back pain require improved understanding of the complex relationships between pain, intradiscal pro-inflammatory cytokines, and structural IVD degeneration. A rat in vivo lumbar IVD puncture model was used to 1) determine the role of TNF alpha in initiating painful IVD degeneration, and 2) identify statistical relationships between painful behavior, IVD degeneration, and intradiscal pro-inflammatory cytokine expression. MethodsLumbar IVDs were punctured anteriorly and injected with TNF alpha, anti-TNF alpha, or saline and compared with sham and naive controls. Hindpaw mechanical hyperalgesia was assayed weekly to determine pain over time. 6-weeks post-surgery, animals were sacrificed, and IVD degeneration, IVD height, and intradiscal TNF alpha and interleukin-1 beta (IL-1 beta) expressions were assayed. ResultsIntradiscal TNF alpha injection increased pain and IVD degeneration whereas anti-TNF alpha alleviated pain to sham level. Multivariate step-wise linear regression identified pain threshold was predicted by IVD degeneration and intradiscal TNF alpha expression. Pain threshold was also linearly associated with IVD height loss and IL-1 beta. DiscussionThe significant associations between IVD degeneration, height loss, inflammation, and painful behavior highlight the multifactorial nature of painful IVD degeneration and the challenges to diagnose and treat a specific underlying factor. We concluded that TNF alpha is an initiator of painful IVD degeneration and its early inhibition can mitigate pain and degeneration. Intradiscal TNF alpha inhibition following IVD injury may warrant investigation for its potential to alter downstream painful IVD degeneration processes.
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页数:11
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