Oligonucleotide IMT504 ameliorates mechanical and cold allodynia in rats with persistent neuropathic pain

CASADEI, MAILÍN; FIORE, ESTEBAN; CORONE,L M. FLORENCIA; LEIGUARDA, CANDELARIA; GARCIA, MARIANA; MAZZOLINI, GUILLERMO; VILLAR MARCELO; MONTANER, ALEJANDRO; BRUMOVSKY, PABLO

Boston

Congreso; 17th annual IASP World Congress on Pain; 2018

International Association for the Study of Pain (IASP)

Summary: The aim of this work is to analyze the antiallodynic and antiinflammatory effect of an experimental oligodeoxynucleotide (IMT504), in the context of chronic neuropathic pain. We observe that IMT504 is highly efficient in reducing mechanical and cold allodynia in rats with spared nerve injury. The effect is quick and long-lasting. In addition, IMT504 induces a marked reduction in bone marrow colony forming units-fibroblasts, potentially suggesting the induction of mesenchymal stem cell mobilization during treatment.Aim of Investigation: Here we evaluated the effect of the systemic administration of a single dose of IMT504 on the development of mechanical and thermal allodynia in an experimental model of neuropathic pain, as well as the effect on bone marrow mesenchymal stem cells. IMT504, the prototype of a major class of immunomodulatory oligodeoxynucleotides (ODN), is able to modulate cells of the immune system, such as lymphocyte B cells, plasmocytoid dendritic cells, CD56+ cells and mesenchymal stem cells (MSC). We previously showed that IMT504 prevents or ameliorates pain progression in rats with acute compression of the sciatic nerve. More recently, we also showed that chronic inflammation of the hindpaw in rats is prevented or ameliorated by multiple doses of IMT504 in rats.Methods: All procedures were performed on adult male Sprague-Dawley rats.The spared nerve injury (SNI) model was used to induce persistent neuropathic pain. In all experiments, the ODN IMT504, with sequence 5′-TCATCATT TTGTCATTTTGTCATT-3′ (developed by Immunotech SA, Argentina) was used. Rats were treated either with IMT504 at a single dose of 6 mg/kg, administered 7 days post-SNI or with saline solution (vehicle-treated group). Mechanical and cold allodynia were measured both in contralateral and ipsilateral hindpaws, before and for several days and weeks after treatment. For analysis of the effect of IMT504 on bone marrow MSC, the colony forming units-fibroblasts (CFU-F) assay was used. Bone marrow stromal cells (BMSC) were collected from femur and tibia from groups of rats sacrificed a different survival times (7, 8, 14 and 28 days) and cultured during 14 days, at which time CFU-F were observed and counted using an optical inverted microscope.