Vagus nerve stimulation modulates visceral pain-related affective memory

Abstract

Within a biopsychosocial model of pain, pain is seen as a conscious experience modulated by mental, emotional and sensory mechanisms. Recently, using a rodent visceral pain assay that combines the colorectal distension (CRD) model with the conditioned place avoidance (CPA) paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC) activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Electrical vagus nerve stimulation (VNS) has become an established therapy for treatment-resistant epilepsy. VNS has also been shown to enhance memory performance in rats and humans. High-intensity VNS (400 μA) immediately following conditional training significantly increases the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, VNS (400 μA) had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593). Low-intensity VNS (40 μA) had no effect on CRD-induced CPA. Electrophysiological recording showed that VNS (400 μA) had no effect on basal and CRD-induced ACC neuronal firing. Further, VNS did not alter CRD-induced visceral pain responses suggesting high intensity VNS facilitates visceral pain aversive memory independent of sensory discriminative aspects of visceral pain processing. The findings that vagus nerve stimulation facilities visceral pain-related affective memory underscore the importance of memory in visceral pain perception, and support the theory that postprandial factors may act on vagal afferents to modulate ongoing nature of visceral pain-induced affective disorder observed in the clinic, such as irritable bowel syndrome.