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Papers of the Week

Papers: 2 Dec 2023 - 8 Dec 2023

2023 Dec 06

Sci Transl Med




Editor's Pick

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


Jiang W, Glaeser JD, Kaneda G, Sheyn J, Wechsler JT, Stephan S, Salehi K, Chan JL, Tawackoli W, Avalos P, Johnson C, Castaneda C, Kanim LEA, Tanasansomboon T, Burda JE, Shelest O, Yameen H, Perry TG, Kropf M, Cuellar JM, Seliktar D, Bae HW, Stone LS, Sheyn D


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.