• Jeffrey E Arle, Kristen W Carlson, Longzhi Mei, Nicolae Iftimia, and Jay L Shils.
• Department of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Neurosurgery, Harvard Medical School, Boston, MA, USA.
• Neuromodulation. 2014 Oct 1;17(7):642-55; discussion 655.

ObjectiveStimulation of axons within the dorsal columns of the human spinal cord has become a widely used therapy to treat refractory neuropathic pain. The mechanisms have yet to be fully elucidated and may even be contrary to standard "gate control theory." Our hypothesis is that a computational model provides a plausible description of the mechanism by which dorsal column stimulation (DCS) inhibits wide dynamic range (WDR) cell output in a neuropathic model but not in a nociceptive pain model.Materials And MethodsWe created a computational model of the human spinal cord involving approximately 360,000 individual neurons and dendritic processing of some 60 million synapses--the most elaborate dynamic computational model of the human spinal cord to date. Neuropathic and nociceptive "pain" signals were created by activating topographically isolated regions of excitatory interneurons and high-threshold nociceptive fiber inputs, driving analogous regions of WDR neurons. Dorsal column fiber activity was then added at clinically relevant levels (e.g., Aβ firing rate between 0 and 110 Hz by using a 210-μsec pulse width, 50-150 Hz frequency, at 1-3 V amplitude).ResultsAnalysis of the nociceptive pain, neuropathic pain, and modulated circuits shows that, in contradiction to gate control theory, 1) nociceptive and neuropathic pain signaling must be distinct, and 2) DCS neuromodulation predominantly affects the neuropathic signal only, inhibiting centrally sensitized pathological neuron groups and ultimately the WDR pain transmission cells.ConclusionWe offer a different set of necessary premises than gate control theory to explain neuropathic pain inhibition and the relative lack of nociceptive pain inhibition by using retrograde DCS. Hypotheses regarding not only the pain relief mechanisms of DCS were made but also regarding the circuitry of pain itself, both nociceptive and neuropathic. These hypotheses and further use of the model may lead to novel stimulation paradigms.© 2014 International Neuromodulation Society.

17 keywords...

hide…