Background & Aims

Pain is an innate protective perception that is essential for survival. Conscious perception of pain is mediated by an evolutionarily conserved neural circuit that includes nociceptive primary afferent input from the body to spinal cord dorsal horn neurons. After spinal cord injury (SCI), sensory perception changes chronically and neuropathic pain develops. Evidence of aberrant anatomical and physiological plasticity occurs in nociceptors including increased sprouting of primary afferent fibers and heightened ectopic activity which are associated with the development of chronic pain and SCI. However, how this plasticity impacts the sensory neurons in the dorsal horn of the spinal cord has not been explored. The current study characterizes the electrophysiological properties of cervical dorsal horn neurons in naïve rats, rats that received unilateral C5 contusive SCI, and rats receiving SCI plus ablation of primary nociceptors.

Methods

All rats but a naïve group received a moderate, unilateral C5 spinal cord contusion. Half of the SCI rats received microinjections into the ipsilateral C7-8 dorsal root ganglia of saporin conjugated to isolectin-B4 to ablate mechanical nociceptors. Rats underwent von Frey and Hargreaves’ assessments weekly for 4 weeks. On Week 5, all rats underwent terminal in vivo single unit recordings under urethane anesthesia electrophysiology activity of cervical spinal cord sensory neurons was measured in response to various stimuli of the forepaw (i.e., brush, pinch, squeeze). Location of mechanically sensitive neurons was mapped onto the spinal cord, and amplitude and latency of firing were quantified. Data were analyzed using Spike2 software. Spike thresholds and latency of stimuli were represented by peristimulus time histograms. Spikes were band-pass filtered, sorted based by shape. Spike clusters were represented by principal component analyses.

Results

We identified 3 distinct cell types: low threshold, high threshold and wide dynamic range neurons in the C7-8 dorsal horn where sensory information from the paw is processed. Low threshold neurons responded to brushing and air puff while high-threshold cells responded to pressure and pinch. WDR neurons were identified by a response to both low and high-threshold stimuli. SCI and SCI-nociceptor ablated groups had increased ectopic activity of dorsal horn neurons compared to naive. Most cells responded to high threshold stimuli. Only some cells showed a significant response to low threshold air puff. Nonetheless, some cells responded well to all other stimuli which perhaps indicates there is a large quantity of WDR neurons recorded based on preliminary analysis. We are currently mapping the laminar distribution of recorded cells within the spinal cord and adding to our dataset.

Conclusions

To summarize our findings, we have been able to categorize different cell types based on our choice of stimuli. Initial analysis suggests that most cells might be considered WDR neurons based on their ability to respond to stimuli of differing intensities. These results remain consistent with previous findings where WDR neurons that respond to noxious and innocuous stimuli and can be found wide-spread throughout the dorsolateral quadrant of the spinal cord. In the future, we plan to observe how these categories of cells are impacted by thermal stimulation in future experiments.

References

N/A

Presenting Author

Patrick J, McGinnis

Poster Authors

Patrick McGinnis

BSc

Drexel University College of Medicine

Lead Author

John R. Walker

Msc

Drexel University college of medicine

Lead Author

Tatiana Bezdudnaya

Drexel University college of medicine

Lead Author

Vitaly Marchenko MD,PHD

Drexel University college of medicine

Lead Author

Megan R. Detloff

Drexel University College of Medicine

Lead Author

Topics

  • Models: Chronic Pain - Neuropathic