Acute and long-term VNS effects on pain perception in a case of treatment-resistant depression

Vagus Nerve Stimulation (VNS) is approved by the FDA for treatment of both epilepsy and depression. Recent work has shown that VNS acutely affects pain perception in humans, actually increasing pain sensitivity momentarily while the device is firing. It is unclear how this acutely increased sensitivity might change over time with treatment and how it might relate to longer-term therapeutic effects of VNS on pain. We describe a patient with treatment-resistant depression and a history of severe lumbar degenerative disease with resultant chronic low back pain. His depression and pain symptoms both seemed to respond to VNS. He eventually stopped all medications and remained depression and pain free for 35 months with no change in his device settings. Sixty-six months after VNS implantation and 64 months after his initial clinical antidepressant response, under single-blind conditions, we performed quantitative sensory testing with laboratory thermal pain procedures during acute VNS-on and -off conditions. Interestingly, despite a significant and profound anti-nociceptive clinical response for the previous 35 months, he had significant increases in painfulness ratings while the VNS device was actively firing compared with device-off conditions. This case suggests that VNS-induced acute increases in pain sensitivity can coexist with a clinical anti-nociceptive response. If the acutely increased sensitivity sets the stage for the slower chronic anti-pain effects, the increased acute sensitivity does not disappear. Acute and chronic effects of VNS on pain perception merit further research.