Intervertebral Disc Cells Produce Interleukins Found in Patients with Back Pain

Abstract

Objective To examine the link between cytokines in intervertebral disc (IVD) tissues and axial back pain. Design In vitro study with human IVD cells cultured from cadaveric donors and annulus fibrosus (AF) tissues from patients. Results Cultured nucleus pulposus (NP) and AF cells were stimulated with interleukin (IL)-1β. IL-8 and IL-7 gene expression was analyzed using real-time PCR. IL-8 protein was quantified by ELISA. Following IL-1β stimulation, IL-8 gene expression increased 26,541 fold in NP cells and 22,429 fold in AF cells, while protein released by the NP and AF cells increased 2,389 and 1,784 fold, respectively. IL-7 gene expression increased 3.3 fold in NP cells (p<0.05). Cytokine profiles in AF tissues collected from patients undergoing surgery for back pain (painful group) or scoliosis (controls) were compared by cytokine array. IL-8 protein in the AF tissues from patients with back pain was 1.81 fold of that in controls. IL-7 and IL-10 in AF tissues from the painful group were, respectively, 6.87 and 4.63 times greater than the corresponding values in controls (p<0.05). Conclusion Inflammatory mediators found in AF tissues from patients with discogenic back pain are likely produced by IVD cells, and may play a key role in back pain.

Salmon-derived thrombin inhibits development of chronic pain through an endothelial barrier protective mechanism dependent on APC

“…Although the roles of TNF-α and IL-1β in the development of pain are well-established, the contributions of IL-7 and IL-12 to pain are controversial (56-59). Clinically, IL-7 transcription and expression were shown to increase in intervertebral disc cells in patients with low back pain (59).…”

“…Clinically, IL-7 transcription and expression were shown to increase in intervertebral disc cells in patients with low back pain (59). However, serum concentrations of IL-7 in patients with cancer-related pain increase within 3 hours of an analgesic opioid treatment (57).…”

Cell therapy for the degenerating intervertebral disc

“…(103, 104) The high levels of proinflammatory mediators found in disc tissue from patients undergoing fusion for discogenic back pain suggest that production of proinflammatory mediators within the IVD may be a major factor in the genesis of a painful lumbar disc. (11, 12, 98, 99) These findings strongly suggest that in addition to the commonly used histology and extracellular matrix composition, inflammatory markers may be used as outcome measures in response to cell therapy. However, among the 50 studies, only 2 examined local inflammation.…”

“…Discography is a valuable tool since positive findings during discography correlate with levels of cytokines/chemokines in the tissue, thus providing a pathophysiological basis for discogenic back pain. (11, 12) Discography, however, may cause further IVD degeneration,(13) due to needle puncture damage and the toxicity of injected anesthetics and contrast media. (14–16) Based on these observations, only patients with severe axial back pain that is suspected to be due to degenerative disc disease are clinical candidates for discography.…”

“…(96, 97) Inflammation in the IVD tissues is also increasingly recognized to be associated with back pain. (11, 12, 98–100) More recently, serum biomarkers have been reported that vary with diagnosis. (101, 101, 101, 101, 102, 102) In particular, serum levels of IL-6 were significantly higher in subjects with LBP compared with control subjects.…”