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

• DOI: 10.1002/jsp2.1014
• Publication Date: 2018-05-21T09:29:30Z
• Authors: Thomas W. Evashwi...; Alon Lai; Hironobu Watanabe; Jonathan M. Salandra; Beth A. Winkelstein; Samuel K. Cho; Andrew C. Hecht; James C. Iatridis
• Keywords: Orthopedic surgery; 03 medical and health sciences; 0302 clinical medicine; intervertebral disc degeneration; disc height; discogenic pain; infliximab; low back pain; RD701-811; Research Articles; axial back pain; 3. Good health

BackgroundPainful intervertebral disc (IVD) degeneration has tremendous societal costs and few effective therapies. Intradiscal tumor necrosis factor‐alpha (TNFα) 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 TNFα 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 TNFα, anti‐TNFα, 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 TNFα and interleukin‐1 beta (IL‐1β) expressions were assayed.ResultsIntradiscal TNFα injection increased pain and IVD degeneration whereas anti‐TNFα alleviated pain to sham level. Multivariate step‐wise linear regression identified pain threshold was predicted by IVD degeneration and intradiscal TNFα expression. Pain threshold was also linearly associated with IVD height loss and IL‐1β.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 TNFα is an initiator of painful IVD degeneration and its early inhibition can mitigate pain and degeneration. Intradiscal TNFα inhibition following IVD injury may warrant investigation for its potential to alter downstream painful IVD degeneration processes.