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High-dose polystyrene nanoparticles trigger aberrant activation of the MAPK pathway in spinal cord and pain hypersensitivity

Journal of Nanobiotechnology 2026
Yuan Yin, Yuan Yin, Panyang Gu, Haibo Jiang, Yumei Yang, Shujun Wang, Feng Yuan, Wenrui Zhong, Miao Chen, Miao Chen, Meichun Deng

Summary

Scientists found that people working in plastic manufacturing environments showed abnormal pain sensitivity, and lab studies revealed that high doses of tiny plastic particles can cause increased pain by triggering inflammation in the spinal cord. The plastic particles activate immune cells and pain pathways in ways that make the nervous system oversensitive to pain signals. This research suggests that exposure to microplastics from our plastic-filled environment could potentially affect how we experience pain, though more studies are needed to understand real-world health impacts.

Polymers
Body Systems
Models

The widespread use of plastic products has led to a serious environmental problem, with nanoplastics ubiquitously contaminating the environment and sustaining human exposure, yet the impacts of nanoplastics on human health remain poorly understood. In this study, based on preliminary epidemiological investigations, we found that abnormal pain perception exists in populations chronically exposed to manufacturing environments that mainly produce polystyrene plastics. Further mechanistic studies demonstrated that high-dose polystyrene nanoparticles (PS NPs) induce pain hypersensitivity and elucidated their molecular underpinnings. Upon high-dose PS NPs exposure, microglia in the spinal dorsal horn internalized a fraction of the PS NPs, which were subsequently found to bind to mitogen-activated-protein-kinases (MAPK) pathway components (ERK, JNK, and p38). Molecular dynamics simulations further suggested that this binding could induce conformational alterations in the MAPK components, potentially enhancing the flexibility of their phosphorylation sites (Thr-X-Tyr) and thereby facilitating activation by upstream kinases. As a canonical inflammatory and pain-associated pathway, MAPK activation elevates neuroinflammatory cascades in the spinal dorsal horn, driving neuronal hyperexcitability and, consequently, pain hypersensitivity. Notably, the PS NPs-induced hypersensitivity was reversed by microglial depletion (PLX5622) and inhibition of the MAPK pathway. Collectively, our findings delineate PS NPs-triggered sensory pathophysiology and establish a proof-of-concept mechanistic nexus between environmental pollutants and aberrant somatosensation.

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