Discussion
depression, Depression, Pain, pain
Although stimulation with 4 Hz showed an interesting trend eliciting a better pain relief than any other tested frequencies in a blinded fashion, this difference was not statistically significant in this study. The same trend was seen using the Beck Depression Inventory, but results from McGill Pain Questionnaire and EQ-5D-5L favored stimulation with 20 Hz—again without statistical significance. This second phase of the original clinical trial was underpowered due to the sample size and possibly also because the effect of 4-Hz stimulation might be only discretely better than that of 20-Hz stimulation. Similar to the important case series of Dr. Chapman and his team tapering stimulation frequencies from 16 to 4 Hz, no statistical significance was found when comparing pre- and post-tapering pain intensity scores in a group of 20 patients [Dorsal root ganglion stimulation possibly acts activating low-threshold mechanoreceptors, which report fine touch sensation to the spinal cord and potentially reduce the perception of pain [The reason why even lower stimulation frequencies might be more effective than 20 Hz itself could be the long-term depression of synaptic transmission in the substancia gelatinosa, a phenomenon once described in rats by Sandkühler et al. His team stimulated dorsal roots with 1-Hz stimulation for 15 min and measured the amplitude of excitatory postsynaptic potentials in the substancia gelatinosa. When the intensity of conditioning stimulation was raised to 10 V, recruiting a maximum of Aδ fibers, there was a robust long-term depression of synaptic transmission for the entire duration of the recording, that lasted for 160 min [Low-frequency stimulation of the DRG might not only have a long-lasting effect, but also intuitively reduces the amount of electrical charge used by the patients and could possibly mean a relevant extension of battery lifetime. Further clinical trials on the issue should consider these characteristics when assessing the effect of low-frequency stimulation and maybe use longer test phases and longer washout periods. Larger trials could even be able to identify a significant difference in pain intensity scores, possibly confirming the clear trend of this study favoring lower stimulation frequencies. Ideally, a study with a large sample size could also analyze the effect of different frequencies in each pain etiology, as different entities target different nerve fibers and are therefore possibly better addressed by specific frequency ranges.Although the results were not statistically significant, the test of different stimulation frequencies should be offered to individual patients under DRG-S seeking better results. Changes in pain relief are sometimes dramatic in sensitive patients, but a thorough evaluation could only be done in the course of weeks and assessing not only pain intensity scores, but also indicators of quality of life. Even when lower stimulation frequencies provide similar results to standard 20-Hz stimulation in the individual patient, we would recommend the lowest efficient frequency with a view to saving battery lifetime.