Background & Aims

The insula is a key area for pain processing. We have preliminary evidence that direct stimulation of the anterior insula increases heat pain threshold in humans [1]. We aim to investigate the safety and feasibility of insula deep brain stimulation (DBS) for chronic neuropathic pain management.

Methods

A two-staged clinical trial was designed for twelve patients with medication-refractory chronic neuropathic pain. Phase 1 of the clinical trial involves stereotactic implantation of multi-contact intracerebral depth electrodes for brain mapping and multi-day continuous electroencephalogram (EEG) monitoring of the bilateral insula. Subjects who ‘respond’ (increase in heat pain threshold and/or decrease in clinical or experimental pain) to the direct insular stimulation in phase 1 will advance to phase 2 for permanent DBS system implantation and a randomized, sham-stimulation controlled trial. Subjects’ pain experience will be collected in their natural environments and social contexts via ecological momentary assessment (EMA) methodologies.

Results

Four subjects have completed phase 1. Stimulating posterior insula commonly evoked numbness or tingling sensations (n=4). Afterdischarges (n=4) and clinical seizure (n=1) were seen with higher current stimulations. All subjects met the responder’s criteria. Exploratory EEG spectral analysis showed that high chronic pain is associated with excessive slower alpha oscillations in the posterior insula that were reversed following direct anterior insula stimulation (p < 0.05, n=3).

Conclusions

Stimulation of the insula is well tolerated in the hospital setting. Acute anti-nociceptive responses to electrical stimulation of the anterior insula have been consistently observed. The long-term effects of anterior insula DBS neuromodulation on clinical pain severity and chronicity are still under investigation.

References

1. Anterior insula stimulation increases pain threshold in humans: a pilot study. 2021. Liu CC, Moosa S, Quigg M, Elias WJ. Journal of Neurosurgery; 135(5):1487-1492.

Presenting Author

Chang-Chia Liu

Poster Authors

Chang-Chia Liu

Ph.D.

University of Virginia

Lead Author

Shayan Moosa

M.D.

University of Virginia School of Medicine

Lead Author

Patrick Finan

Ph.D.

University of Virginia School of Medicine

Lead Author

Mark Quigg

M.D.

University of Virginia School of Medicine

Lead Author

W. Jeff Elias

M.D.

University of Virginia School of Medicine

Lead Author

Topics

  • Mechanisms: Biological-Systems (Physiology/Anatomy)