Mechanisms for the Clinical Utility of Low-Frequency Stimulation in Neuromodulation of the Dorsal Root Ganglion

BACKGROUND: Dorsal root ganglion stimulation (DRG-S) involves the electrical modulation of the somata of afferent neural fibers to treat chronic pain. DRG-S has demonstrated clinical efficacy at frequencies lower than typically used with spinal cord stimulation (SCS). In a clinical study, we found that the frequency of DRG-S can be tapered to a frequency as low as 4 Hz with no loss of efficacy. This review discusses possible mechanisms of action underlying effective pain relief with very low-frequency DRG-S. MATERIALS AND METHODS: We performed a literature review to explore the role of frequency in neural transmission and the corresponding relevance of frequency settings with neuromodulation. FINDINGS: Sensory neural transmission is a frequency-modulated system, with signal frequency determining which mechanisms are activated in the dorsal horn. In the dorsal horn, low-frequency signaling (25 Hz) are excitatory. Physiologically, low-threshold mechanoreceptors (LTMRs) fibers transmit or modulate innocuous mechanical touch at frequencies as low as 0.5-5 Hz, while nociceptive fibers transmit pain at high frequencies. We postulate that very low-frequency DRG-S, at least partially, harnesses LTMRs and the native endogenous opioid system. Utilizing lower stimulation frequency decreases the total energy delivery used for DRG-S, extends battery life, and facilitates the development of devices with smaller generators