Analgesic Effects of Novel Spinal Cord Stimulation Waveforms in Rats With Painful Tibial Nerve Injury

Neuropathic pain is associated with hyperexcitability of spinal cord dorsal horn neurons. Spinal cord stimulation (SCS) can reduce this hyperexcitability and provide analgesia. We evaluated the effects of two novel SCS waveforms, designed with long pulse widths and short interpulse intervals with slowly varying amplitudes, on neuropathic pain behaviors and dorsal horn neuronal activity in a rat model of tibial nerve injury (TNI).

Rats underwent TNI followed by implantation of epidural stimulation leads. Novel waveforms, specifically stochastic amplitude modulated pulse train and delayed discharge pulse train, were delivered at 60% and 80% of motor threshold and compared with DeRidder Burst stimulation. Behavioral assays included von Frey and pin-prick testing for mechanical hypersensitivity, dynamic weight bearing for ongoing pain, and acute place preference for motivational aspects of pain. In vivo extracellular recordings from dorsal horn wide-dynamic-range (WDR) neurons at lamina V depth (500-600 μm) were performed before and after stimulation.

Both novel waveforms significantly increased withdrawal thresholds to mechanical stimulation (p < 0.01), reduced pin-evoked hypersensitivity (p < 0.05), restored weight-bearing asymmetry (p <0.05), and increased time spent in stimulation-paired compartments (p < 0.01). Electrophysiology confirmed increased thresholds and reduced evoked firing rates of WDR neurons.

Novel SCS waveforms using varying amplitudes reduce behavioral and electrophysiologic correlates of neuropathic pain in rats. Sub-motor-threshold stimulation with varying amplitude trains can attenuate dorsal horn hyperexcitability. These results support further investigation of waveform design as a strategy for improving neuromodulation therapies.