title: Spinal Cord Stimulation in Chronic Pain: Mode of Action.
abstract: METHODS
  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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  N /A.
authors.affiliation: Millennium Pain Center, Bloomington, IL.|Illinois Wesleyan University, Bloomington, IL.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vallejo
authors.affiliation: Nevro Corporation, Menlo Park, CA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Bradley
authors.affiliation: Wake Forest University Health Sciences, Winston-Salem, NC.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Kapural
mesh_terms: D059350:Chronic Pain / Q000175:diagnosis / Q000628:therapy*; D003198:Computer Simulation; D004599:Electric Stimulation Therapy / Q000379:methods; D006801:Humans; D009437:Neuralgia / Q000175:diagnosis / Q000628:therapy; D010147:Pain Measurement / Q000379:methods; D010292:Paresthesia / Q000175:diagnosis / Q000628:therapy; D013116:Spinal Cord / Q000502:physiology; D062187:Spinal Cord Stimulation / Q000379:methods*