IMT504 - An anti-nociceptive oligodeoxynucleotide with potential impact in neuropeptidergic systems

HÖKFELT T; VILLAR, M.J.; CORONEL, M.F.; RUBIONE, JULIA; MIGUEL, BERNARDO; BRUMOVSKY, PR

Washington

Conferencia; Neuropeptide signaling: Bridging Cell Biology, Neurophysiology and Behavior; 2023

Howard Hughes Medical Institute

Neuropathic pain, characterized by direct injury or disease of the somatosensory nervous system, is a complex condition associated with neuronal dysfunction. Over the last 4 decades, our research on plasticity during neuropathic pain has shown that neuropeptides and signaling through their associated receptors, both in primary afferent and spinal cord neurons, directly impact neuronal excitability. Moreover, we revealed that two such neuropeptides, galanin and neuropeptide tyrosine (NPY), bear therapeutic potential.However, a growing body of evidence suggests that the cause of neuropathic pain is not only restricted to changes in neuronal phenotype and activity; it also involves interactions with glial and immune cells. Interestingly, peptides and several associated receptors, including galanin, NPY and also opioids, are expressed by immune cells and appear intimately related to immune system modulation. The so-called neuroimmune interactions between these different systems are far from being fully understood.We previously showed that direct administration of mesenchymal stem cells (MSCs) into dorsal root ganglia (DRGs) results both in neuropathic pain prevention, as well as attenuation of injury-induced changes in galanin, NPY and the NPY Y1-receptor in primary afferent neurons. More recently, we began addressing the role of IMT504, a non-coding, synthetic oligodeoxynucleotide, which, by inducing pro-migratory (towards injured nerves and DRGs) and phenotypic changes in MSCs, exerts remarkable anti-allodynic and anti-inflammatory effects, in rats with neuropathic or inflammatory pain. Remarkably, the anti-allodynic effects are transiently blocked by naloxone, suggesting that the actions of IMT504 may also involve opioidergic signaling.In this research presentation, besides exposing in better detail the evidence highlighted above, our objective is to propose the hypothesis that use of IMT504 as a research tool may help reveal an original and rich peptidergic signaling network involving neurons, MSCs, glial and immune cells, with impact on chronic pain, and with the potential to be therapeutically meaningful.