Spinal Cord Stimulation using time-dynamic pulses achieves faster and longer reversal of allodynia compared to tonic pulses in a rat model of neuropathic pain

Spinal cord stimulation (SCS) utilizing time-dynamic pulses (TDPs) is an emergent field of neuromodulation that continuously and automatically modulates pulse parameters. We previously demonstrated that TDPs delivered for 60 min at sub-paresthesia amplitudes significantly reversed allodynia in a rat model of neuropathic pain. Because we observed these anti-allodynic effects persisted post-cessation, we investigated the extended temporal dynamics of SCS-induced analgesia. We hypothesized that TDPs achieve a longer duration of analgesia than tonic stimulation. Both TDPs and tonic stimulation reversed PWT to near pre-chronificiation levels within 30 minutes. Most TDPs exhibited significantly slower ramp-up slope (analgesia wash-in rates) compared to tonic stimulation (amplitude modulation: 0.16{+/-}0.03 min-1, pulse width modulation: 0.18{+/-}0.05 min-1, stochastic modulation: 0.17{+/-}0.04 min-1, tonic: 0.31{+/-}0.06 min-1). All TDPs showed slower wind-down slopes (analgesia wash-out rates) compared to tonic (-0.29{+/-}0.07 min-1), with pulse width modulation (-0.11{+/-}0.02 min-1) reaching significance. Extending SCS from 60 to 90 minutes revealed all TDPs maintain analgesic efficacy longer than tonic stimulation, which decreased significantly at both 75 and 90 minutes (from 13.8{+/-}0.5 g to 12.3{+/-}0.9 g and to 11.0{+/-}0.5 g, respectively). Although TDPs and tonic stimulation comparably mitigated allodynia, TDPs generally exhibited slower temporal dynamics, suggesting longer-lasting analgesic effects and potentially different mechanisms of action.