Central effects of stellate ganglion block mediated by the vagus nerve? An alternate hypothesis for treating PTSD

Emerging clinical studies have demonstrated that stellate ganglion block (SGB) can significantly reduce PTSD symptoms. While the exact mechanism is still unknown, it has been proposed that SGB reduces sympathetic tone by reducing peripheral levels of nerve growth factor (NGF) and norepinephrine (NE). Interestingly, the therapeutic benefits of SGB can be sustained up to 3–6 months, despite the procedure's use of a temporary local anesthetic. Such effects may be attributed to SGB's central effects on fear-related brain regions, including the hypothalamus, hippocampus, and amygdala. Lipov and colleagues hypothesized a mechanism by which SGB may have central effects. Specifically, it was hypothesized that NGF can retrogradely transport to the brain from the periphery and that SGB works by reducing both central and peripheral NGF levels, leading to a subsequent decrease in NE and sympathetic tone. Lipov et al. further hypothesized that reduced NGF/NE levels in the hippocampus and amygdala are key to facilitating fear memory extinction. However, no study to date has fully verified the model. Here, we aim to expand upon Lipov's article and propose an alternate hypothesis: SGB's ability to “reset” the autonomic nervous system and affect key brain regions is mediated by the vagus nerve. Indeed, the vagus nerve sends both efferent and afferent information from the medulla oblongata of the brain stem. It is conceivable that SGB's peripheral effects may work through the vagus nerve by modulating fear-related brain regions responsible for homeostatic autonomic control and fear memory. Ultimately, this article provides an alternate hypothesis on the mechanism of SGB, encourages integrative studies on both the stellate ganglion and vagus nerve, and may help guide treatment strategies for PTSD.