Intervertebral disc human nucleus pulposus cells associated with back pain trigger neurite outgrowth in vitro and pain behaviors in rats.
Publication Year:
2023
PubMed ID:
38055799
Funding Grants:
Public Summary:
Low back pain is often caused by wear and tear of the discs between our spine bones. But exactly how these damaged discs cause pain isn’t fully understood. In this study, researchers discovered a special type of cell inside these discs that seems to trigger pain when the disc starts to degenerate. They found that under certain conditions, these cells change and start sending signals that can activate nerve cells linked to pain. When they put these changed cells into healthy discs in rats, the animals showed signs of increased pain and inflammation. This new understanding of how these disc cells cause pain could lead to new treatments that directly target these cells to help reduce back pain.
Scientific Abstract:
Low back pain (LBP) is often associated with the degeneration of human intervertebral discs (IVDs). However, the pain-inducing mechanism in degenerating discs remains to be elucidated. Here, we identified a subtype of locally residing human nucleus pulposus cells (NPCs), generated by certain conditions in degenerating discs, that was associated with the onset of discogenic back pain. Single-cell transcriptomic analysis of human tissues showed a strong correlation between a specific cell subtype and the pain condition associated with the human degenerated disc, suggesting that they are pain-triggering. The application of IVD degeneration-associated exogenous stimuli to healthy NPCs in vitro recreated a pain-associated phenotype. These stimulated NPCs activated functional human iPSC-derived sensory neuron responses in an in vitro organ-chip model. Injection of stimulated NPCs into the healthy rat IVD induced local inflammatory responses and increased cold sensitivity and mechanical hypersensitivity. Our findings reveal a previously uncharacterized pain-inducing mechanism mediated by NPCs in degenerating IVDs. These findings could aid in the development of NPC-targeted therapeutic strategies for the clinically unmet need to attenuate discogenic LBP.
