Dual-frequency spinal cord stimulation increases responder rates for treatment of neuropathic pain

Spinal cord stimulation (SCS) is an established treatment for chronic pain. However, there is a clear opportunity for improvement as only approximately 60% of patients report a 50% or greater reduction in pain. In this study, we propose a novel approach, termed dual-frequency spinal cord stimulation (dfSCS), that is designed to exploit the underlying putative mechanisms of SCS-Gate Control Theory-by dispersing SCS-mediated excitation in time while preserving SCS-mediated inhibition. We simulate dfSCS, using a validated computational model of the spinal cord dorsal horn, by delivering 2 simultaneous stimulation frequencies to Aβ dorsal column axons representing the painful and surrounding region dermatomes. We experimentally compared dfSCS patterns that the model indicated were robust to variation in the axonal populations activated, as well as progressive loss of GABAergic inhibition typical in chronic pain, against conventional single-frequency SCS in male spared nerve injured rats. Dual-frequency spinal cord stimulation targeted to vertebral levels T12/T13, where the largest population of dorsal column projections from the hypersensitive sural nerve territory and surrounding dermatomes are located, increased responder rates over conventional stimulation. The optimal dfSCS frequency combination depended on both the orientation of the bipolar electrode stimulation and the rostrocaudal placement over the cord. Paw withdrawal threshold testing revealed either 2 Hz:54 Hz or 25 Hz:40 Hz as the most effective stimulation pair, depending on mediolateral vs rostrocaudal electrode configuration and vertebral level of stimulation, with rodent responder rates up to 100%. Overall, dfSCS is a promising approach to improving the efficacy of SCS for neuropathic pain.