Efficacy of virtual reality assisted guided imagery (VRAGI) in a home setting for pain management in patients with advanced cancer: protocol for a randomised controlled trial.

INTRODUCTION: Patients with advanced cancer often experience high levels of debilitating pain and pain-related psychological distress. Although there is increasing evidence that non-pharmacological interventions are needed to manage their pain, pharmacologic modalities remain the preferred treatment . Guided imagery is a form of focused relaxation that helps create harmony between the mind and body and has been shown to significantly improve cancer pain. Our study presents Virtual Reality Assisted Guided Imagery (VRAGI) as a complementary treatment modality to manage chronic pain in patients with cancer. We will conduct a randomised controlled trial to test its impact on patients with advanced cancer in a home setting. METHODS AND ANALYSIS: We will recruit 80 patients from Prisma Health, a tertiary-level healthcare centre based in Greenville, South Carolina, USA. The prospective 2×2 randomised controlled trial will randomise participants into four groups: (1) VRAGI, (2) laptop-assisted guided imagery, (3) VR (no guided imagery) and (4) laptop (no guided imagery). Patients allocated to VR groups will be trained to use a head-mounted display that immerses them in 3D audio-video content. The non-VR group will use a laptop displaying 2D video content. We will collect measures before and during the 3-week intervention as well as 3 weeks after the intervention ends. Measures will include patient-reported outcomes of pain, anxiety, depression and fatigue in addition to opioid use. The primary objective of the current study is to assess the efficacy of VRAGI on pain in the home setting. The secondary objective is to assess the efficacy of VRAGI on opioid use, anxiety, depression and fatigue. ETHICS AND DISSEMINATION: This study was approved by the Prisma Health Institutional Review Board (#Pro00114598) in November 2021. All participants enrolled in the study will provide written informed consent. Dissemination will be through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05348174, clinicaltrials.gov.

Mu opioid receptor regulation of glutamate efflux in the central amygdala in response to predator odor.

The amygdala plays an important role in the responses to predator threat. Glutamatergic processes in amygdala regulate the behavioral responses to predator stress, and we have found that exposure to ferret odor activates glutamatergic neurons of the basolateral amygdala [BLA] which are known to project to the central amygdala [CeA]. Therefore, we tested if predator stress would increase glutamate release in the rat CeA using in vivo microdialysis, while monitoring behavioral responses during a 1 h exposure to ferret odor. Since injections of mu opioid receptor [MOR] agonists and antagonists into the CeA modulate behavioral responses to predator odor, we locally infused the MOR agonist DAMGO or the MOR antagonist CTAP into the CeA during predator stress to examine effects on glutamate efflux and behavior. We found that ferret odor exposure increased glutamate, but not GABA, efflux in the CeA, and this effect was attenuated by tetrodotoxin. Interestingly, increases in glutamate efflux elicited by ferret odor exposure were blocked by infusion of CTAP, but CTAP did not alter the behavioral responses during predator stress. DAMGO alone enhanced glutamate efflux, but did not modulate glutamate efflux during predator stress. These studies demonstrate that ferret odor exposure, like other stressors, enhances glutamate efflux in the CeA. Further, they suggest that activation of MOR in the CeA may help shape the defensive response to predator odor and other threats.