10.2217/pmt-2015-0013 © 2016 Future Medicine Ltd Neuromodulation is defined as a functional change in the CNS neuronal activity through electrical or pharmacological mediation. Applications of neuromodulation have been apparent for centuries, notably in ancient Rome when court physician Scribonius Largus utilized the electrical shock of a torpedo fish as a remedy for headaches and gouty arthritis [1]. The early 20th century made way for the ‘electreat’ device, a precursor to common day peripheral nerve stimulators, which made neuromodulation a widely available commercial therapy for the treatment of pain. Yet no scientific explanation could reliably explain the physiologic mechanisms behind electricity as a therapeutic modality for pain control. Gate control & pain processing Various theories attempting to explain pain perception circulated during the first part of the 20th century. In 1965, Melzack and Wall proposed their ‘gate control theory’, which provides a more complex and detailed explanation behind the mechanisms of pain transmission and processing. The fundamental concept to their theory suggests that transmission (T) cells within the spinal cord function as a ‘gate keeper’ in the perception of pain. These cells receive excitatory and inhibitory inputs from large and small peripheral fibers within the substatia gelatinosa, and downward projecting cerebral centers. Collectively, these pathways determine whether or not the painful stimuli pass the ‘gate’ to perception [2]. COMMENTARY