Modulation of Intracortical S1 Responses Following Peripheral Nerve High-Frequency Electrical Stimulation in Danish Landrace Pigs

Long-term potentiation (LTP) has been extensively studied with rodents and human subjects to understand pain mechanisms. This phenomenon remains relatively less explored in pigs, even though pigs present a suitable translational model for neurophysiological research. This study aimed to investigate changes in the spike activity in the primary somatosensory cortex (S1) in response to spinal LTP-like neuroplasticity induced by high-frequency electrical stimulation (HFS) in Danish landrace pigs. Six animals were investigated (two controls and four interventions). A 16-channel multi-electrode array was implanted into the S1. A tripolar cuff was placed around the ulnar nerve. HFS (15 mA, 100 Hz, 1 ms) was induced on the ulnar nerve branches to induce LTP-like neuroplasticity, followed by non-nociceptive stimulation to probe the S1 response. Peristimulus time histograms (PSTHs) were constructed based on the neuronal spikes detected from S1. For the intervention group, the PSTH showed a significant increase in the area under the curve (AUC) 45 min (T2 phase) after applying the HFS. These results were in line with findings based on local-field potentials, i.e., the cortical excitability increased immediately after intervention and became significantly greater during the T2 phase. The result of this study is believed to be an essential contribution to developing a translational, large-animal model of LTP-like pain to bridge research between animal models and clinical applications.