Ricardo Vallejo1,2, Kerry Bradley3, Leonardo Kapural4. 1. Millennium Pain Center, Bloomington, IL. 2. Illinois Wesleyan University, Bloomington, IL. 3. Nevro Corporation, Menlo Park, CA. 4. Wake Forest University Health Sciences, Winston-Salem, NC.
Abstract
STUDY DESIGN: Literature review. OBJECTIVE: A review of the literature that presents a perspective on mechanisms of actions behind spinal cord stimulation (SCS) therapy for chronic pain. SUMMARY OF BACKGROUND DATA: SCS is an effective therapeutic alternative for the treatment of intractable chronic pain. Its application has been mostly based on the gate control theory of pain. Computational models have been fundamental on the understanding of clinical observations and the design of therapies that provide optimal neuromodulation. Research has provided insight into the involvement of specific neurotransmitters that support segmental and supraspinal mechanisms of action. METHODS: A literature review was performed with emphasis on mechanisms of action for SCS including the effects of electrical fields on spinal cord structures based on computational models and preclinical and clinical explorations. RESULTS: This review provides background on the development of SCS, which has been driven around a paresthesia-based paradigm as a result of the gate control theory. A review of computational models emphasizes their importance on our current understanding of the mechanism of action and clinical optimization of therapy. Electrophysiology and molecular biology have provided a closer, yet narrow, view of the effect of SCS on neurotransmitters and their receptors, which have led to the formulation of segmental and supraspinal mechanisms. Literature supporting the involvement of glial cells in chronic pain and their characteristic response to electrical fields should motivate further investigation of mechanisms involving neuroglia. Finally, a review of recent results paresthesia-free strategies should encourage research on mechanisms of action. CONCLUSION: The mechanisms of SCS have been extensively studied and several consistent phenomena have emerged. The activation of A-beta fibers to induce paresthesia also involve neurotransmitter release via segmental and supraspinal pathways. Despite advancements, much remains to be understood, particularly as new stimulation strategies are developed. LEVEL OF EVIDENCE: N /A.
STUDY DESIGN: Literature review. OBJECTIVE: A review of the literature that presents a perspective on mechanisms of actions behind spinal cord stimulation (SCS) therapy for chronic pain. SUMMARY OF BACKGROUND DATA: SCS is an effective therapeutic alternative for the treatment of intractable chronic pain. Its application has been mostly based on the gate control theory of pain. Computational models have been fundamental on the understanding of clinical observations and the design of therapies that provide optimal neuromodulation. Research has provided insight into the involvement of specific neurotransmitters that support segmental and supraspinal mechanisms of action. METHODS: A literature review was performed with emphasis on mechanisms of action for SCS including the effects of electrical fields on spinal cord structures based on computational models and preclinical and clinical explorations. RESULTS: This review provides background on the development of SCS, which has been driven around a paresthesia-based paradigm as a result of the gate control theory. A review of computational models emphasizes their importance on our current understanding of the mechanism of action and clinical optimization of therapy. Electrophysiology and molecular biology have provided a closer, yet narrow, view of the effect of SCS on neurotransmitters and their receptors, which have led to the formulation of segmental and supraspinal mechanisms. Literature supporting the involvement of glial cells in chronic pain and their characteristic response to electrical fields should motivate further investigation of mechanisms involving neuroglia. Finally, a review of recent results paresthesia-free strategies should encourage research on mechanisms of action. CONCLUSION: The mechanisms of SCS have been extensively studied and several consistent phenomena have emerged. The activation of A-beta fibers to induce paresthesia also involve neurotransmitter release via segmental and supraspinal pathways. Despite advancements, much remains to be understood, particularly as new stimulation strategies are developed. LEVEL OF EVIDENCE: N /A.
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