Characterization of neuroinflammation and periphery-to-CNS inflammatory cross-talk in patients with disc herniation and degenerative disc disease

Abstract

The aim of the study was to identify inflammatory cytokines/chemokines associated with neuroinflammation and periphery-to-CNS inflammatory cross-talk in degenerative disc disease (DDD) and lumbar disc herniation (LDH), common causes of low back pain (LBP). A secondary aim was to investigate the associations between cytokines and symptom severity.

Methods: In total, 40 DDD and 40 LDH patients were recruited from a surgical waiting list, as well as 39 healthy controls (HC) and 40 cerebrospinal fluid (CSF) controls. The subjects completed questionnaires and pressure algometry was performed at the lumbar spine and forearm. The CSF, serum and disc tissues were collected during surgery. Inflammatory mediators TNF, INFg, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13 and MCP1 were analysed by immunoassay (Meso Scale Discovery) and quantitative real-time polymerase chain reaction (qPCR) was used for analysis of IL-6, IL-8, MCP1 and TSPO expression in intervertebral discs (IVDs).

Results: In the LDH group, we found elevated IL-8 concentrations in CSF indicating neuroinflammation, while IL-8 and MCP1 concentrations in serum were lower compared to HC. The IVD expression of IL-6, IL-8 and TSPO was lower in LDH patients compared to DDD. LDH patients had a positive correlation between IL-8 concentrations in CSF and serum and IL-8 in CSF was associated with higher pain intensity and increased spinal pressure pain sensitivity. The MCP1 concentration in serum was associated with higher global pain ratings and increased spinal pressure pain sensitivity, while IL-6 serum concentration correlated with the intensity of the neuropathic pain component (leg pain) in LDH patients. IVD expression of TSPO in LDH patients was associated with increased intensity of back pain. No differences were found in cytokine CSF concentrations between DDD patients and CSF controls, but DDD patients had lower IL-8 and MCP1 serum concentrations than HC. In female DDD patients, IL-8 and MCP1 concentrations in serum were associated with increased intensity of back pain.

Conclusion: Our results suggest that neuroinflammation mediated by elevated IL-8 concentrations in CSF and IL-8 mediated periphery-to-CNS inflammatory cross-talk contributes to pain in LDH patients and suggest a link between TSPO expression in discs and low back pain.

Keywords: Chemokines; Cytokines; Degenerative disc disease (DDD); Interleukin-6 (IL-6); Interleukin-8 (IL-8); Intervertebral discs; Low back pain (LBP); Lumbar disc herniation (LDH); Monocyte chemotactic protein 1 (MCP1); Neuroinflammation; The translocator protein (TSPO).