IMT504 provides analgesia by modulating cell infiltrate and inflammatory milieu in rats with hindpaw inflammation

LEIGUARDA C; POTILINSKI, C; RUBIONE J; TATE P; VILLAR MJ; MONTANER AD; BISAGNO V; CONSTANDIL, L; BRUMOVSKY P

JOURNAL OF NEUROIMMUNE PHARMACOLOGY

SPRINGER

Lugar: Berlin; Año: 2020

1557-1890

Oligodeoxynucleotide (ODN) IMT504 is a non-CPG, non-coding synthetic ODN exerting long-lasting anti-allodynic effects upon multiple systemic administrations. However, its mechanisms of anti-nociceptive action are still poorly understood. In the present study in male adult rats undergoing complete Freund´s adjuvant-induced hindpaw inflammation, we focused in the analysis of the inflamed paw, in order to determine if the anti-nociceptive effects of IMT504 relate to modulation of infiltrating inflammatory cells of different kinds, and on the expression of several associated cytokines and β-endorphin. Pain-like behavior tests, Evans blue extravasation, flow-cytometry, proteome profiler cytokine array and Elisa tests were used. We show that even use of a single 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 were associated with quick reductions in hindpaw edema, downregulated B-cell and macrophages counts, and a moderate upregulation in CD8+ T-cell counts. Moreover, IMT504 treatment induced a profound downregulation of several leukocyte adhesion proteins, chemokines and cytokines, as well as of β-endorphin, plus a moderate upregulation of IL-10. Altogether, we demonstrate that the anti-nociceptive actions of IMT504 relate to modulation of the peripheral immune system at the site of injury, favoring a switch from pro- to anti-inflammatory conditions, and provide further support to its use against chronic inflammatory pain.