Effects of transcranial ultrasound stimulation of primary somatosensory cortex and ventral posterolateral nucleus of the thalamus on acute pain perception

ABSTRACT: Noninvasive neuromodulatory techniques provide important means to study the role of brain regions activated by nociceptive stimuli in pain perception. This study investigates the role of the primary somatosensory cortex (S1) and the ventral posterolateral nucleus (VPL) of the thalamus in acute pain perception using transcranial ultrasound stimulation (TUS). Twenty-five healthy participants underwent a double-blind, sham-controlled, within-subject experimental design. Transcranial ultrasound stimulation was applied to the left S1 and left VPL in separate sessions, with quantitative sensory testing performed before and after stimulation. Measures included heat pain threshold (HPT), heat pain tolerance (HPTol), warm detection threshold (WDT), mechanical detection threshold (MDT), and pressure pain threshold (PPT). Stimulation of the left S1 significantly lowered HPT (P = 0.013) and HPTol (P = 0.040) on the contralateral hand, with median differences of -0.6°C (IQR [-1.20, 0.35]) and -0.2°C (IQR [-1.00, 0.3]), respectively. In addition, both S1 and VPL stimulation led to bilateral reductions in WDT (P < 0.001), with median decreases ranging from -0.25°C to -0.35°C (IQRs ranging from -0.95 to 0.30). No significant changes were observed in MDT (P > 0.89) or PPT (P > 0.78). These findings suggest the involvement of S1 in pain perception, particularly in modulating heat pain sensitivity. The modulation of warm detection by both S1 and VPL further suggests that TUS can influence sensory processing at multiple levels of the somatosensory pathway. Further research is needed to replicate the present findings, elucidate the underlying biophysical mechanisms, and optimize stimulation protocols for clinical applications.