Intraspinal microstimulation simultaneously rebalances motor and nociceptive transmission in chronic spinal cord injury

Introduction:: Spinal cord injury (SCI) results in devastating physiological changes at and below the level of the lesion, including reduced motor output, autonomic dysregulation, impaired pelvic floor function and SCI-related neuropathic pain (SCI-NP). Electrical spinal stimulation (ESS) therapies are a promising approach to treating these issues. However, spinal stimulation-based approaches for SCI recovery are generally parametrized for motor rehabilitation alone and rarely assess for potential off-target effects on other systems. Interestingly, the effectiveness of ESS approaches for SCI motor rehabilitation and ESS approaches for managing non-SCI-related neuropathic pain (e.g., low back pain, complex regional pain syndrome) seems to rely, at least partially on similar neural mechanisms. Namely, these mechanisms are the recruitment of sensory afferent pathways and interneuron networks. Thus, it may be possible to use ESS approaches to simultaneously increase voluntary motor output and ameliorate neuropathic pain after SCI. Here, we investigate this possibility by assessing the potential effects of ESS for SCI motor rehabilitation on spinal pain pathways.

Materials and Methods:: We used spike train analyses to characterize the effects of motor-targeted intraspinal microstimulation (ISMS) on spinal nociceptive transmission post-SCI in 15 adult, male Sprague-Dawley rats. All experiments were approved by the IACUC of Washington University. We conducted electrophysiological recordings 6-8 weeks after a T8 contusion with microelectrode arrays implanted at the L5 dorsal root entry zone. ISMS was delivered to the spinal motor pools, and transmission in sensory pathways was characterized in the dorsal horns. We mechanically stimulated the L5 dermatome with innocuous and/or noxious forces (respectively) before, during, and after ISMS. Our primary outcome measures were changes in the firing rate [Hz] of nociceptive specific (NS) and wide dynamic range (WDR) neurons during nociceptive transmission. Changes were quantified by comparing the average maximum instantaneous firing rates before, during, and after 30min of ISMS.


Results, Conclusions, and Discussions:: We found that even a single 30 min session of motor-targeted ISMS in the injured spinal cord modulated neural transmission in nociceptive pathways of the dorsal horn. Indeed, ~60% of NS and WDR neuronal populations, respectively, reduced their maximum firing rate during induced nociceptive transmission after ISMS compared to before ISMS. We also found the firing rate of WDR neurons progressively decreased with increasing ISMS duration and remained depressed after ISMS was discontinued.

Our results suggest that motor-targeted ISMS may have the ability to immediately modulate spinal nociceptive transmission and to induce neural plasticity in spinal sensory networks in the chronically injured spinal cord. These actions appear to result in a net decrease in spinal responses to nociceptive sensory feedback. These results suggest that it may be possible to optimize ESS paradigms to simultaneously increase voluntary motor output and ameliorate neuropathic chronic pain after SCI.


Acknowledgements (Optional): : This work was supported by NINDS grant R01 NS111234 (to J.G.M.).

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