biostudies-literatureCasadei MCONICYT FONDECYTNINDS NIH HHSNIHAgencia Nacional De Promoción Científica Y Tecnológica104508https://www.ebi.ac.uk/biostudies/studies/S-EPMC11283994biostudies-literatureUnknown25(8)Postamputation pain is currently managed unsatisfactorily with neuron-targeted pharmacological and interventional therapies. Non-neuronal pain mechanisms have emerged as crucial factors in the development and persistence of postamputation pain. Consequently, these mechanisms offer exciting prospects as innovative therapeutic targets. We examined the hypothesis that engaging mesenchymal stem cells (MSCs) would foster local neuroimmune interactions, leading to a potential reduction in postamputation pain. We utilized an ex vivo neuroma model from a phantom limb pain patient to uncover that the oligodeoxynucleotide IMT504 engaged human primary MSCs to promote an anti-inflammatory microenvironment. Reverse translation experiments recapitulated these effects. Thus, in an in vivo rat model, IMT5The journal of painMesenchymal Stem Cell Engagement Modulates Neuroma Microenviroment in Rats and Humans and Prevents Postamputation Pain.PMC11283994R01 NS114653Rubione JMengelle DBrumovsky PRGuerri-Guttenberg RAFiore ECasadei MMontaner AVillar MJConstandil-Cordova LRomero-Sandoval AEMiguel BfalseMesenchymal Stem Cell Engagement Modulates Neuroma Microenviroment in Rats and Humans and Prevents Postamputation Pain.Postamputation pain is currently managed unsatisfactorily with neuron-targeted pharmacological and interventional therapies. Non-neuronal pain mechanisms have emerged as crucial factors in the development and persistence of postamputation pain. Consequently, these mechanisms offer exciting prospects as innovative therapeutic targets. We examined the hypothesis that engaging mesenchymal stem cells (MSCs) would foster local neuroimmune interactions, leading to a potential reduction in postamputation pain. We utilized an ex vivo neuroma model from a phantom limb pain patient to uncover that the oligodeoxynucleotide IMT504 engaged human primary MSCs to promote an anti-inflammatory microenvironment. Reverse translation experiments recapitulated these effects. Thus, in an in vivo rat model, IMT52024-01-01T00:00:00Z2024 Aug2026-03-18T13:22:45.978Z2025-08-18T09:53:59.944ZS-EPMC112839943848485410.1016/j.jpain.2024.03.004