SAN2020

IMT504 is a non-CPG, non-coding synthetic ODN exerting long-lasting anti-allodynic effects in rats undergoing unilateral hindpaw inflammation. The purpose of the present study is to address cellular and molecular mechanisms at the site of injury potentially underlying the anti-nociceptive role of IMT504. Analysis of pain-like behavior, locomotor activity, histology, cell infiltration by flow-cytometry, secreted proteins by protein microarrays or ELISA (β-endorphins) in the inflamed hindpaws were employed to study the impact of a single subcutaneous administration of IMT504 in male adult rats undergoing complete Freund´s adjuvant-induced hindpaw inflammation. We show that a single subcutaneous dose of IMT504 results in a 6-week-long full reversal of mechanical and cold allodynia, compromising neither acute pain perception nor locomotor activity. The anti-nociceptive effects of systemic IMT504 correlated with reductions in hindpaw dorsoventral thickness, plasma extravasation, decreases in B-cell and macrophage counts, and an increase in CD8+ T-cell counts. Moreover, a profound downregulation in several pro-inflammatory cytokines as well as of β-endorphin, plus mild upregulation of IL-10, were also observed at the site of injury. Altogether, we provide new evidence demonstrating that the anti-nociceptive actions of IMT504 relate to modulation of the peripheral immune system at the site of injury, and support its use as a novel anti-inflammatory drug against chronic pain.