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tection and vibratory detection thresholds also significantly increased with HFS compared to ON states (p = 0.04 and p = 0.01, respectively). In addition, HFS significantly decreased 10-and 40-gram pinprick detection compared to OFF states (both p = 0.01). No significant differences between OFF, ON and HFS states were seen in thermal and thermal pain detection. Conclusion: HFS is a new means of modulating chronic pain. The mechanism by which HFS works seems to differ from that of traditional SCS, offering a new platform for innovative advancements in treatment and a greater potential to treat patients by customizing waveforms.

Astrocytes, the most abundant and structurally complex glial cells of the central nervous system, are proposed to play an important role in modulating the activities of neuronal networks, including respiratory rhythm-generating circuits of the preBötzinger complex (preBötC) located in the ventrolateral medulla of the brainstem. However, structural properties of astrocytes residing within different brainstem regions are unknown. In this study astrocytes in the preBötC, an intermediate reticular formation (IRF) region with respiratory-related function, and a region of the nucleus tractus solitarius (NTS) in adult rats were reconstructed and their morphological features were compared. Detailed morphological analysis revealed that preBötC astrocytes are structurally more complex than those residing within the functionally distinct neighboring IRF region, or the NTS, located at the dorsal aspect of the medulla oblongata. Structural analyses of the brainstem microvasculature indicated no significant regional differences in vascular properties. We hypothesize that high morphological complexity of preBötC astrocytes reflects their functional role in providing structural/metabolic support and modulation of the key neuronal circuits essential for breathing, as well as constraints imposed by arrangements of associated neurons and/or other local structural features of the brainstem parenchyma.