Good vibrations to treat inflammatory arthritis

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Science Translational Medicine  03 Apr 2019:
Vol. 11, Issue 486, eaax1721
DOI: 10.1126/scitranslmed.aax1721


Ultrasound stimulation of the vagus nerve via the spleen triggers the neural-immune reflex to dampen inflammatory arthritis.

Can vibrating your spleen relieve those achy knees? The cholinergic anti-inflammatory pathway, wherein the parasympathetic vagus nerve transmits to the adrenergic splenic nerve to influence splenic immune cells, is a relatively new mechanism by which researchers seek to modulate the immune system. Recent clinical studies demonstrated that implanted vagus nerve electrode cuffs can trigger the neural-immune reflex to dampen chronic inflammatory responses. A new study from Zachs et al. investigated whether ultrasound stimulation of the spleen could noninvasively trigger the same pathway, a controversial strategy in the emergent field of autonomic neuromodulation.

In this study, the authors sought to identify a therapeutic window of ultrasound parameters to achieve consistent and repeatable results. They explored a range of parameters in a murine model of inflammatory arthritis to select optimal ultrasound settings for splenic nerve stimulation, and they attempted to elucidate a mechanism via single cell RNA sequencing of splenic immune cells. The authors found that ultrasound pressure amplitude of 333 to 350 kPa, with a duration between 6 to 20 min, achieved optimal results. Additionally, they identified lymphocyte genes modulated by splenic ultrasound stimulation, including those involved with regulation of the cytoskeleton which may impact lymphocyte polarization or migration.

This study demonstrates a potentially translatable, noninvasive method of reducing inflammatory responses. The authors mention a companion paper wherein comparable results were achieved by an independent research group, which strengthens the authors’ findings. One caveat, however, is that the mice in this study required daily ultrasound treatment to achieve an effect, and the required focus of the ultrasound transducer directly on the spleen necessitates trained delivery of this therapy. Unless clinical results are superior to pharmacological options, it is unlikely this therapy will achieve widespread adoption, considering convenience alone. With a pilot clinical trial recently initiated by the authors, perhaps we will receive the answer to these questions sooner rather than later.

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