Subjective Analgesic Effects of Naloxone and Virtual Reality

This study is designed to test a specific hypothesis exploring the neurophysiologic
mechanism(s) that underlie the pain- relieving effects of immersive Virtual Reality (VR) as
a non-pharmacologic pain management technique, using healthy volunteers experiencing
carefully controlled thermal and/or electrical pain in the laboratory. Over the past
decade, our research group has performed a series of NIH-funded investigations of VR
analgesia - in both the clinical pain and laboratory pain settings - demonstrating its
clinical efficacy and safety. In the current study we will test pharmacologic manipulation
of VR analgesia (with the opioid analgesia antagonist naloxone). We anticipate that this
theoretical work will provide a foundation for future clinical applications of immersive VR
- whether used alone or in combination with other analgesic agents - and make immersive VR a
more effective and more widely used analgesic tool for the treatment of clinical pain.

Our previous work with immersive VR indicates that its use during a painful event can reduce
subjective pain reports during both acute clinical and laboratory pain by 20-50% [1].
Furthermore, we have shown that effective VR analgesia is associated with reduced
pain-related brain activity that is quantitatively and qualitatively comparable to
clinically relevant doses of systemic opioid analgesics [2]. The laboratory pain protocol
proposed in the current application is identical to the UW HSD-approved protocol used in our
previous studies (#25296 - "Reducing Brief Thermal and Electrical Pain"). What is
specifically different in the current protocol is the use of naloxone to determine whether
VR analgesia operates through an endogenous opioid-dependent mechanism or not. The results
of this study will not only suggest the mechanism of action of VR analgesia, but also allow
us to more effectively apply immersive VR analgesia in the clinically pain setting through
its thoughtful combination with well-established pharmacologic analgesic techniques, such as
opioid analgesia administration.

The specific aim of this study and the hypothesis it tests are as follows: To determine the
extent to which subjective analgesic effects of VR analgesia are inhibited by opioid
receptor antagonism with naloxone. Hypothesis - VR analgesia will not be inhibited by
systemic opioid receptor antagonism, suggesting that VR analgesia is not mediated by release
of endogenous opiates and/or by activation of opioid-dependent descending central nervous
system pathways.