Mechanism of Action of Peripheral Nerve Stimulation

Introduction

The underlying mechanism of peripheral nerve stimulation (PNS) has always been thought to be an extension of the “Gate Theory of Pain,” traditional spinal cord stimulation (SCS) applied to peripheral nerves. While this theory may still hold true, recent studies have shown that the Gate Theory alone cannot solely explain the principles behind PNS.

Gate Theory

A thorough discussion of neuromodulation first requires an understanding of the Gate Theory developed by Ronald Melzack and Patrick Wall in 1965. In its simplest understanding, nonnociceptive inputs “close the gate” to nociceptive inputs at the dorsal horn of the spinal cord, preventing the transmission of pain signals. In a practical manner, this theory is commonly demonstrated with children at the park: a child may fall off a swing, sustaining a painful abrasion to their knee. The child’s caregiver, sensing their child’s distress, will commonly start rubbing the affected area in an effort to distract the child from their pain while at the same time decreasing the pain transmission.

On a molecular level, the transmission of pain first begins with a nociceptive input sensed by the afferent nerve. The nociceptive inputs are carried both by the thinly myelinated Aδ and unmyelinated C fibers. These small nerve fibers inactivate inhibitory interneurons at the dorsal horn of the spinal cord, “opening the gate” and allowing for the transmission of pain. If there is large Aβ fiber stimulation (from pressure, vibration, etc.), these myelinated A fibers will activate those inhibitory interneurons, “closing the gate” and blocking the transmission of pain ( Fig. 3.1 ).

Spinal Cord Stimulation

In a patient with chronic pain, these pain pathways have become aberrant. They have undergone central sensitization. While the exact mechanism of central sensitization and the influence of SCS is not yet quite fully understood, some theories on how it modulates neuropathic pain are widely accepted. In the dorsal horn, after nerve injury, there has been shown to be an increase in activity of the wide dynamic range (WDR) neurons. When WDR neurons increase their activity, they produce less of the inhibitory gamma-aminobutyric acid (GABA) neurotransmitter and produce more of the excitatory glutamate neurotransmitter. SCS decreases WDR activity, therefore increasing the concentrations of GABA and decreasing glutamate in the dorsal horn.

Mechanism of Action

PNS is defined as electric stimulation performed on the peripheral nerve system and applied to a specific nerve. These same principles noted above for SCS are being applied to peripheral nerves in PNS. In fact, much of the technology originally developed for SCS is currently being tested with various peripheral nerves to treat refractory chronic pain conditions that are not responsive to conventional treatments. PNS involves electrically stimulating the given peripheral nerve by placing an electrode adjacent to it.