Modulation of mesenchymal stem cells, glial cells and the immune system by oligodeoxynucleotides as a novel multi-target therapeutic approach against chronic pain

P.R. BRUMOVSKY; M. CASADEI; C. LEIGUARDA; M.F. CORONEL; J. RUBIONE; A.D. MONTANER; M.J. VILLAR

Frontiers in Clinical Drug Research (CNS and Neurological Disorders)

Bentham

Año: 2022; p. 226 - 268

Abstract: Despite our growing understanding of chronic pain mechanisms, an alarming proportion of patients worldwide remains refractory to treatment. Chronic pain is complex, involving the interaction of both neuronal and non-neuronal systems. Several studies focused on immune, glial and mesenchymal stem cells (MSCs) have recently revealed key roles for these non-neuronal players in the initiation and perpetuation of chronic pain. The complexity of chronic pain is reflected by the difficulty of its therapeutic control, in particular when using mono-target drugs. A good proportion of these drugs target neuronal pathways, and serious concerns arise when it comes to the use of opioids and abuse liability. In contrast, novel pain drugs targeting non-neuronal components of chronic pain are scarce. Exceptions include classical non-steroidal anti-inflammatory drugs, or those modulating trophic factors, although their use remains restricted to presence of appropriate targets. Synthetic oligodeoxynucleotides have been used as immune system modulators for the last 15 years. One of them, IMT504, a non-CpG oligodeoxynucleotide, exhibits remarkable, long-lasting anti-allodynic and anti-inflammatory properties upon single-dose systemic administration in rodent models of inflammatory or neuropathic pain. Mounting evidence suggests that the beneficial effects of IMT504 relate to actions on the immune system, glial cells and MSCs. In this state-of-the-art chapter we address the current knowledge 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 mechanisms of action will be key in the identification of novel and effective multi-target pain drugs without abuse liability.