Neural population dynamics reveal that motor-targeted intraspinal microstimulation preferentially depresses nociceptive transmission in spinal cord injury-related neuropathic pain

The purpose of this study is to determine whether intraspinal microstimulation (ISMS) intended to enhance voluntary motor output after spinal cord injury (SCI) modulates neural population-level spinal responsiveness to nociceptive sensory feedback. The study was conducted in vivo in three cohorts of rats: neurologically intact, chronic SCI without behavioral signs of neuropathic pain, and chronic SCI with SCI-related neuropathic pain (SCI-NP). Nociceptive sensory feedback was induced by application of graded mechanical pressure to the plantar surface of the hindpaw before, during, and after periods of sub-motor threshold ISMS delivered within the motor pools of the L5 spinal segment. Neural population-level responsiveness to nociceptive feedback was recorded throughout the dorso-ventral extent of the L5 spinal segment using dense multi-channel microelectrode arrays. Whereas motor-targeted ISMS reduced nociceptive transmission across electrodes in neurologically intact animals both during and following stimulation, it was not associated with altered nociceptive transmission in rats with SCI that lacked behavioral signs of neuropathic pain. Surprisingly, nociceptive transmission was reduced both during and following motor-targeted ISMS in rats with SCI-NP, and to an extent comparable to that of neurologically intact animals. The mechanisms underlying the differential anti-nociceptive effects of motor-targeted ISMS are unclear, although they may be related to differences in the intrinsic active membrane properties of spinal neurons across the cohorts. Nevertheless, the results of this study support the notion that it may be possible to purposefully engineer spinal stimulation-based therapies that afford multi-modal rehabilitation benefits, and specifically that it may be possible to do so for the individuals most in need – i.e., those with SCI-related movement impairments and SCI-NP.