| First Author | Garrity R | Year | 2023 |
| Journal | Brain Behav Immun | Volume | 112 |
| Pages | 220-234 | PubMed ID | 37315702 |
| Mgi Jnum | J:337751 | Mgi Id | MGI:7506059 |
| Doi | 10.1016/j.bbi.2023.06.011 | Citation | Garrity R, et al. (2023) Fibroblast-derived PI16 sustains inflammatory pain via regulation of CD206(+) myeloid cells. Brain Behav Immun 112:220-234 |
| abstractText | Originally identified in fibroblasts, Protease Inhibitor (PI)16 was recently shown to be crucial for the development of neuropathic pain via effects on blood-nerve barrier permeability and leukocyte infiltration, though its impact on inflammatory pain has not been established. Using the complete Freund's Adjuvant inflammatory pain model, we show that Pi16(-/-) mice are protected against sustained inflammatory pain. Accordingly, intrathecal delivery of a PI16 neutralizing antibody in wild-type mice prevented sustained CFA pain. In contrast to neuropathic pain models, we did not observe any changes in blood-nerve barrier permeability due to PI16 deletion. Instead, Pi16(-/-) mice display reduced macrophage density in the CFA-injected hindpaw. Furthermore, there was a significant bias toward CD206(hi) (anti-inflammatory) macrophages in the hindpaw and associated dorsal root ganglia. Following CFA, intrathecal depletion of CD206(+) macrophages using mannosylated clodronate liposomes promoted sustained pain in Pi16(-/-) mice. Similarly, an IL-10 neutralizing antibody also promoted sustained CFA pain in the Pi16(-/) when administered intrathecally. Collectively, our results point to fibroblast-derived PI16 mediating substantial differences in macrophage phenotype in the pain neuroaxis under conditions of inflammation. The co-expression of PI16 alongside fibroblast markers in human DRG raise the likelihood that a similar mechanism operates in human inflammatory pain states. Collectively, our findings may have implications for targeting fibroblast-immune cell crosstalk for the treatment of chronic pain. |
