Bone marrow stromal cells migrate to dorsal root ganglia, induce changes in neuropeptides and neuromodulators expression and reduce allodynia after sciatic nerve constriction

M.F. CORONEL; P.L. MUSOLINO; M.J. VILLAR

IByME, Buenos Aires, Argentina

Congreso; VIII Jornadas Multidisciplinarias de la Sociedad Argentina de Biología; 2006

Sociedad Argentina de Biología

Peripheral nerve injury triggers neuropathic pain and induces changes in neuropeptide expression. Following brain injury, bone marrow stromal cells (MSCs) migrate to the lesioned hemisphere and mediate functional recovery. In this study we have analyzed the localization of MSCs administered to rats subjected to a sciatic nerve constriction. We have also assessed the expression of different molecules involved in pain transmission, as well as thermal and mechanical sensitivities. MSCs were isolated from adult rat tibiae and femurs, cultured in DMEM and labelled with Hoechst. 2 x 105 cells were injected into the right L4-dorsal root ganglia (DRGs) of rats subjected to a single ligature nerve constriction. Animals were tested for mechanical and thermal withdrawal thresholds after 1, 3 and 7 days. Lumbar DRGs were dissected out, cut, observed using a fluorescence microscope and processed for immunohistochemistry. MSCs acquired a perineuronal localization in the injected ganglia and migrated to the other ipsilateral lumbar DRGs. Nerve lesion induced a marked increase in the expression of the neuropeptides NPY and galanin and the neuronal isotype of nitric oxide synthase (nNOS) in primary afferent neurons. There was also a decrease in the number of cells expressing NPY-Y1 receptor (Y1r). These changes were prevented by the administration of MSCs. In parallel, both mechanical and thermal allodynias induced by nerve constriction were significantly decreased in MSC-transplanted animals. These results suggest that MSCs may modulate pain generation by modifying NPY, galanin, Y1r and nNOS expression in primary afferent neurons after sciatic nerve lesion.