Long-lasting ameliorating effects of the oligodeoxynucleotide IMT504 on mechanical allodynia and hindpaw edema in rats with chronic hindpaw inflammation

摘要

Highlights ? Intraplantar administration of CFA induces long-lasting mechanical allodynia in rats. ? IMT504 is an immune cell modulating oligodeoxynucleotide. ? Systemic IMT504 ameliorates mechanical allodynia and hindpaw inflammation in CFA-treated rats. ? The antiallodynic and anti-inflammatory effects of IMT504 are long lasting. ? IMT504 is a promising molecule against inflammatory pain. Abstract Purpose Previously we showed that systemic administration of IMT504 prevents or ameliorates mechanical and thermal allodynia in rats with sciatic nerve crush. Here we analyzed if IMT504 is also effective in reducing mechanical allodynia and inflammation in rats undergoing hindpaw inflammation. Materials and methods: Male Sprague-Dawley rats received unilateral intraplantar injection of complete Freund?s adjuvant (CFA), and were grouped into: 1) untreated CFA, 2) vehicle-treated CFA, 3) IMT504-treated CFA (5 daily (5*) doses of 20, 2 or 0.2?mg/kg, or 3*2?mg/kg). Na?ve groups were also included. Finally, early (immediately after intraplantar CFA) and late (7?days after intraplantar CFA) IMT504 treatment protocols were also tested. Hindpaw mechanical allodynia, dorsoventral thickness, edema and cellular infiltration of ipsilateral hindpaws were evaluated in all groups. Results: Untreated CFA rats exhibited mechanical allodynia of quick onset (day 1) and long duration (7 weeks inclusive). Early and late treatments with 5*20?mg/kg IMT504 to CFA rats resulted in both quick and long-lasting antiallodynic effects, as compared to untreated CFA rats. This was also the case in CFA rats undergoing late IMT504 treatment at lower doses (3* and 5*2?mg/kg). Very low doses of IMT504 (5*0.2?mg/kg) only showed a mild improvement in withdrawal threshold, never reaching basal levels. Finally, rats treated with 3* or 5*2?mg/kg or 5*0.2?mg/kg exhibited significant decreases in dorsoventral thickness, edema, and inflammatory cell infiltration of the inflamed hindpaw. Conclusion: Early and late administration of IMT504 results in quick and long-lasting reductions in mechanical allodynia and hindpaw edema. While the mechanisms behind these effects remain to be established, data suggests that IMT504 administration could be a promising strategy in the control of inflammatory pain.