Central neuropathic pain (CNP) commonly develops in patients after spinal cord injury (SCI), causing debilitating symptoms and sensory abnormalities to mechanical and thermal stimuli. The biological variability of pain phenotypes in individuals has limited the number of positive outcomes. Thus, it is necessary to investigate the physiological processes contributing to sensory changes that develop over time.
To investigate the physiological processes contributing to neuropathic pain sensory changes and locomotor impairments with sensory phenotypes that develop over time.
Using the tail flick and von Frey tests, we performed hierarchical clustering to determine the subpopulation of rats that developed thermal and mechanical sensory abnormalities. To measure inflammation as a potential mediator of CNP phenotypes, we used flow cytometry and immunohistochemistry. Finally, to assess the secondary effects on locomotor recovery, up to 8 weeks after injury, we used the CatWalk test to assess multiple parameters of gait.
The von Frey test showed a subpopulation of SCI rats that were hyposensitive to mechanical stimuli from 6 to 8 weeks after injury. The tail flick test showed a subpopulation of SCI rats that were hypersensitive to thermal stimuli at 1 week and 3 to 8 weeks after injury. Although there were no differences in inflammatory cells between subpopulations, we did see significant changes in locomotor recovery between rats with and without sensory abnormalities.
The myeloid cell population at large is not affected by mechanical or thermal phenotypes of pain in this model; however, locomotor recovery is impaired depending on the pain phenotype present. Further investigation into acute inflammatory cells may be insightful for predicting the development of pain phenotypes.
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.

Macrophages are not only derived from circulating blood monocytes or embryonic precursors but also expand by proliferation. The origin determines macrophage fate and functions in steady state and pathological conditions. Macrophages predominantly infiltrate fibre-induced mesothelioma tumors and contribute to cancer development. Here, we revealed their ontogeny by comparing the response to needle-like mesotheliomagenic carbon nanotubes (CNT-7) with tangled-like non-mesotheliomagenic CNT-T. In a rat peritoneal cavity model of mesothelioma, both CNT induced a rapid macrophage disappearance reaction (MDR) of MHCIIlow resident macrophages generating an empty niche available for macrophage repopulation. Macrophage depletion after mesotheliomagenic CNT-7 was followed by a substantial inflammatory reaction, and macrophage replenishment completed after 7 days. Thirty days after non-mesotheliomagenic CNT-T, macrophage repopulation was still incomplete and accompanied by a limited inflammatory reaction. Cell depletion experiments, flow cytometry and RNA-seq analysis demonstrated that, after mesotheliomagenic CNT-7 exposure, resident macrophages were mainly replaced by an influx of monocytes, which differentiated locally into MHCIIhigh inflammatory macrophages. In contrast, the low inflammatory response induced by CNT-T was associated by the accumulation of self-renewing MHCIIlow macrophages that initially derive from monocytes. In conclusion, the mesotheliomagenic response to CNT specifically relies on macrophage niche recolonization by monocyte-derived inflammatory macrophages. In contrast, the apparent homeostasis after non-mesotheliomagenic CNT treatment involves a macrophage regeneration by proliferation. Macrophage depletion and repopulation are thus decisive events characterizing the carcinogenic activity of particles and fibres.
Copyright © 2021 Orsi, Palmai-Pallag, Yakoub, Ibouraadaten, De Beukelaer, Bouzin, Bearzatto, Ambroise, Gala, Brusa, Lison and Huaux.