The Analgesic and Antispastic Effects of Epidural Spinal Stimulation Depending on the Frequency and Intensity After Spinal Cord Injury

Neuropathic pain and spasticity after spinal cord injury (SCI) are intractable conditions that represent distinct outcomes of sensory and motor dysfunction. Spinal cord stimulation (SCS) has been proposed as a potential therapy for these conditions. However, the therapeutic effects of different SCS parameters and their underlying mechanisms remain unclear. The present study aimed to investigate the therapeutic effects of a developed epidural SCS system on SCI-induced pain and spasticity, and to explore its underlying mechanisms in modulating microglia activation. Male Sprague-Dawley rats underwent contusive SCI at T10 segment using an Infinite Horizons impactor, and an epidural SCS system was implanted two weeks after SCI. Mechanical sensitivity and spasticity were assessed using paw withdrawal threshold and modified Ashworth scale. Epidural SCS was applied at low frequency (LF; 50 Hz) or high frequency (HF; 1 kHz) with intensities of 40% or 80% of the motor threshold (MT). Sham control rats underwent SCS implantation without electrical stimulation. Immunohistochemistry was performed to evaluate microglia activation in the lumbar spinal segments. HF with 80% MT intensity showed a higher effect on neuropathic pain and spasticity, whereas LF with 40% MT intensity showed a lower effect. Although SCS did not alter the number of microglia in the lumbar spinal segments, both LF and HF with 80% MT intensity significantly decreased the proportion of activated microglia in both dorsal and ventral horns compared with the sham group. These findings show that the epidural SCS with 80% MT effectively alleviates neuropathic pain and spasticity by reducing spinal microglial activation. These results highlight the importance of optimizing stimulation parameters to achieve therapeutic benefits in clinical settings.