Single-dose systemic administration of the oligodeoxynucleotide IMT504 results in long-lasting ameliorating effects on mechanical allodynia and edema in rats with chronic hindpaw inflammation

LEIGUARDA, CANDELARIA; CORONEL M. FLORENCIA; MONTANER ALEJANDRO D.; VILLAR MARCELO; 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 most effective single-dose of an experimental oligodeoxynucleotide (IMT504) to reduce pain due to chronic peripheral inflammation. We observe that a single-dose of 6 mg/kg of IMT504 is highly efficient in reverting mechanical allodynia in rats with unilateral hindpaw inflammation. The effect is quick and long-lasting. A lower single-dose (2 mg/kg) showed a much slower effect, with full reversion of mechanical allodynia observed almost 4 weeks after initiation of treatment. In addition, IMT504 also exerts a partial anti-inflammatory effect, as shown by the reduction in hindpaw edema and dermal inflammatory cell infiltration.Aim of Investigation: IMT504 is a synthetic ODN with the capacity to modulate cells of the immune system, such as lymphocyte B cells, plasmocytoid dendritic cells, CD56+ cells, mesenchymal stem cells (MSCs). We previously showed that the systemic administration of IMT504 prevents or ameliorates mechanical and thermal allodynia in rats with sciatic nerve crush. More recently, we demonstrated that multiple doses of IMT504 reduce mechanical allodynia and inflammation in rats undergoing chronic hindpaw inflammation. Moreover, we observed that early and late administration of IMT504 results in quick and long-lasting reductions in mechanical allodynia and hindpaw edema with a seemingly dose-dependent effect. Here we performed a series of experiments to determine if and at what concentration a single dose of IMT504 was capable of reducing mechanical allodynia and inflammation.Methods: Adult Sprague?Dawley male rats were used in all experiments. Unilateral hindpaw inflammation was induced by intraplantar injection of complete Freund´s adjuvant (CFA). Subcutaneous IMT504 was administered at concentrations of 2, 6 and 10 mg/kg, 7 days after induction of hindpaw inflammation. Control groups included vehicle-treated rats. Mechanical allodynia was tested using the von Frey test before any intervention (basal responses) and at different time-points after injury and IMT504 or vehicle administration, during 7 weeks. Hindpaw inflammation was evaluated by measurement of hindpaw dorsoventral thickness in awake rats. In addition, 7 weeks after injury, rats were perfused using Lana´s fixative and hindpaws dissected out for histological analysis of tissue sections stained with standard hematoxylin- eosin. Thickness of the dermis and the epidermis was measured and dermal inflammatory cell infiltration was evaluated and quantified.