Intervertebral disc human nucleus pulposus cells associated with back pain trigger neurite outgrowth in vitro and pain behaviors in rats.

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Publication Year:
2023
Authors:
Wensen Jiang, Juliane D Glaeser, Giselle Kaneda, Julia Sheyn, Jacob T Wechsler, Stephen Stephan, Khosrowdad Salehi, Julie L Chan, Wafa Tawackoli, Pablo Avalos, Christopher Johnson, Chloe Castaneda, Linda E A Kanim, Teerachat Tanasansomboon, Joshua E Burda, Oksana Shelest, Haneen Yameen, Tiffany G Perry, Michael Kropf, Jason M Cuellar, Dror Seliktar, Hyun W Bae, Laura S Stone, Dmitriy Sheyn
PubMed ID:
38055799
Funding Grants:
Public Summary:
Low back pain is often caused by the degeneration (wear and tear) of the discs between the bones of the spine, known as intervertebral discs (IVDs). But scientists still don’t fully understand what exactly causes pain when these discs start to break down. In this study, researchers discovered a special type of cell inside damaged discs—called nucleus pulposus cells (NPCs)—that appears to trigger pain. By studying single cells from human spinal discs, they found that this cell type was strongly linked to people who experienced disc-related back pain. When researchers exposed healthy disc cells to the same stressful conditions that happen during disc degeneration, those cells changed and started to behave like the pain-triggering ones. In lab models, these altered cells activated nerve cells that sense pain, and when injected into healthy rats, they caused inflammation and heightened pain sensitivity.
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.