Frontiers in Clinical Drug Research - CNS and Neurological Disorders

Volume: 10

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

Author(s): Pablo R. Brumovsky*, Mailín Casadei, Candelaria Leiguarda, María Florencia Coronel, Julia Rubione, Alejandro Montaner and Marcelo J. Villar

Pp: 226-268 (43)

DOI: 10.2174/9789815040678122100007

* (Excluding Mailing and Handling)


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 of 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 nonsteroidal
anti-inflammatory drugs, or those modulating trophic factors, although their
use remains restricted to the 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 to the identification of novel and effective multi-target pain drugs
without abuse liability.

Keywords: Astrocytes, B Lymphocytes, Chronic Pain, Dorsal Root Ganglia, Drugs, Glial Cells, Inflammation, Inflammatory Cells, Macrophages, Mesenchymal Stem Cells, Microglia, Neuroimmune Interaction, Nociception, Oligodeoxynucleotides, Pain, Spinal Cord, T Lymphocytes.

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