Modulation of Mesenchymal Stam Cells, Glyal Cells and the Immune System by Oligodeoxynucleotides as a Novel Multi-target Therapeutic Approach Against Chronic Pain

BRUMOVSKY P; CASADEI M; LEIGUARDA C; CORONEL MF; RUBIONE J; MONTANER A; VILLAR M

Frontiers in Clinical Drug Reserach - CNS and Neurological Disorders

Bentham Science

Año: 2021; p. 226 - 268

Despite our growing understanding of chronic pain mechanisms, analarming proportion of patients worldwide remains refractory to treatment. Chronicpain is complex, involving the interaction of both neuronal and non-neuronal systems.Several studies focused on immune, glial and mesenchymal stem cells (MSCs) haverecently revealed key roles of these non-neuronal players in the initiation andperpetuation of chronic pain. The complexity of chronic pain is reflected by thedifficulty of its therapeutic control, in particular when using mono-target drugs. A goodproportion of these drugs target neuronal pathways, and serious concerns arise when itcomes to the use of opioids and abuse liability. In contrast, novel pain drugs targetingnon-neuronal components of chronic pain are scarce. Exceptions include classical nonsteroidalanti-inflammatory drugs, or those modulating trophic factors, although theiruse remains restricted to the presence of appropriate targets. Syntheticoligodeoxynucleotides have been used as immune system modulators for the last 15years. One of them, IMT504, a non-CpG oligodeoxynucleotide, exhibits remarkable,long-lasting anti-allodynic and anti-inflammatory properties upon single-dose systemicadministration in rodent models of inflammatory or neuropathic pain. Mountingevidence suggests that the beneficial effects of IMT504 relate to actions on the immunesystem, glial cells and MSCs. In this state-of-the-art chapter, we address the currentknowledge of the role of IMT504 over non-neuronal cells, its impact on chronic pain,and its translational potential. We also propose that further analysis on its mechanismsof action will be key to the identification of novel and effective multi-target pain drugswithout abuse liability.