Electrical nerve stimulation and the relief of chronic pain through regulation of the accumulation of synaptic Arc protein

Abstract

Electrical nerve stimulation (ENS) is used in clinical settings for the treatment of chronic pain, but the mechanism underlying its effects remains unknown. ENS has been found to mimic neural activity, inducing the accumulation of Arc in synapses. Activity-dependent synaptic accumulation of Arc protein has been shown to reduce synaptic strength by promoting endocytosis of the AMPA receptors in the synaptic membrane. These receptors play a decisive role in central sensitization, which is one of the main mechanisms underlying chronic pain. It is here hypothesized that ENS induces Arc expression in synapses, where Arc promotes endocytosis of membrane AMPARs that are up-regulated during chronic pain. High frequency and high intensity are characteristics of ENS, which may be effective in the treatment of chronic pain. Stimulation-site of ENS may also influence the outcome of ENS.