Alireza Khajehnasiri - Anesthesiologist and pain fellowship Faculty member of Tehran University ofMedical – Sciences – Dr. Shariati Hospital

Chronic pain greatly impacts the quality of life and socioeconomic welfare of hundreds of millions of patientsworldwide and imposes a great financial burden on the societies. When many other treatment modalities fail,spinal cord stimulation (SCS) becomes a safe and highly effective option, particularly for mixedneuropathic/nociceptive and neuropathic/radicular pain conditions, such as failed back surgery syndrome andcomplex regional pain syndrome. The optimization of this treatment requires the understanding of chronic painand how SCS parameters affect it. Chronic pain involves the activation of neuroinflammatory processes at thespinal cord level, driven by glial cells. Following peripheral nerve injury, ectopic neuronal action potentials leadto neurotransmitter release at synapses, generating action potentials and activating surrounding glial cells. Ithas been shown that glial activation is fundamental in the development and maintenance of chronicneuropathic pain via the disruption of biological processes that are key in maintaining balanced neuron-glialinteractions.Recent advances in stimulation techniques, which have a mechanism of action distinct from traditional SCS,have improved the efficacy and expanded the applicability of spinal cord stimulation. Differential targetmultiplexed (DTM) SCS is a new paresthesia-free stimulation technique that mediates its analgesic effect bymeans of modulating neuron–glial interaction. DTM SCS was developed after demonstrating that conventionalSCS modulated gene expression in the spinal cord at the site of stimulation, and the dorsal root ganglioncorresponding with the nerve injured in an animal model of neuropathic pain. The DTM approach uses multipleelectrical signals for modulating glial cells and neurons and rebalance their interactions.DTM SCS has been shown to be superior to traditional tonic SCS in subjects with chronic intractable radicularlow back pain and other pain conditions. It is a promising new technique that not only may help millions ofpatients in the future, but also may revolutionize our overall understanding of central pain processingmechanisms.