Poster Z14 - Nonlinear firing dynamics in spinal sensory neurons after spinal cord injury and their role in neuropathic pain

Introduction: Spinal cord injury (SCI) results in chronic changes in the spinal cord, including central sensitization of spinal sensory networks leading to SCI-related neuropathic pain (SCI-NP). SCI-NP is often neurologically characterized by reduced nociceptive thresholds as well as amplified or prolonged responses to noxious stimuli, associated with allodynia and hyperalgesia, respectively. These attributes collectively signify membrane dynamics influenced by the activation of persistent inward currents (PICs), implying that certain fundamental aspects SCI-NP may be attributable to this mechanism. Facilitated by dendritic metabotropic glutamate receptors, sensory PICs are excitatory currents through voltage-dependent sodium and calcium channels. However, the role of sensory PICs in neuropathic pain after SCI has not yet been elucidated. Here, we test the hypothesis that spinal sensory neurons in rats with SCI-NP will exhibit firing dynamics consistent with an increased influence of PICs compared to those that lack signs of SCI-NP and to neurologically intact rats.

Materials and

Methods: All procedures were approved by the Institutional Animal Care and Use Committee of Washington University in St. Louis. We implanted dual-shank multielectrode arrays in vivo into the spinal lumbar enlargement of adult male Sprague-Dawley rats with and without chronic SCI and SCI-NP to record multi-unit neural activity. Data was filtered offline, and single-unit activity was extracted via a wavelet-based spike sorting algorithm. Sensory neurons were discerned by an identifiable response to mechanical probing of the peripheral receptive field, and PIC firing dynamics were identified via the archetypal nonlinear firing pattern and the presence of self-sustained firing after sensory feedback was withdrawn. We further characterized PIC-like firing dynamics using features developed for motoneurons, including acceleration slope, attenuation slope, brace height, and duration of afterdischarge.

Results, Conclusions, and Discussions: We find that spinal sensory neurons in rats with SCI-NP present with more PIC-like firing patterns compared with rats that lack SCI-NP and neurologically intact rats. Magnitude and duration of the observed PICs were also observed to be greater in such rats with SCI-NP. Data evaluating instantaneous firing rate and properties of firing patterns including effectiveness of firing (extracellular acceleration and attenuation slopes), inward current stability and robustness (brace height and after discharge duration) will be presented. In addition to disrupted neuromodulatory drive below the level of contusion, these results may suggest that aberrant PICs play a significant role in the presence of SCI-NP after injury.

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