Modulation of thermal pain-related brain activity with virtual reality: evidence from fMRI Hunter G. Ho¡man, CA Todd L. Richards, 1 Barbara Coda, 2 Aric R. Bills, 4 David Blough, 3 Anne L. Richards 1 and Sam R. Sharar 4 Human InterfaceTechnology Lab, and Department of Radiology, Box 352142; 1 Department of Radiology, Box 357115; 3 Department of Pharmacy, Box 357630, University of Washington, 1959 NE Paci¢c, Seattle, WA 98195; 4 Department of Anesthesiology, Box 359724; 2 Department of Anesthesiology, Box 356540, University of Washington, Seattle, WA 98104, USA CA Corresponding Author: hunter@hitL.washington.edu Received 27 January 2004; accepted 17 March 2004 DOI: 10.1097/01.wnr.0000127826.73576.91 This study investigated the neural correlates of virtual reality an- algesia. Virtual reality signi¢cantly reduced subjective pain ratings (i.e. analgesia). Using fMRI, pain-related brain activity was mea- sured for each participant during conditions of no virtual reality and during virtual reality (order randomized). As predicted, virtual reality signi¢cantly reduced pain-related brain activity in all ¢ve regions of interest; the anterior cingulate cortex, primary and sec- ondary somatosensory cortex, insula, and thalamus ( po0.002, corrected). Results showed direct modulation of human brain pain responses by virtual reality distraction. NeuroReport 15:1245^1248  c 2004 Lippincott Williams & Wilkins. Key words: Analgesia; Anterior cingulate cortex; fMRI; Pain; Somatosensory cortex; Virtual reality INTRODUCTION Excessive pain during medical procedures is a widespread problem. Researchers have recently begun using immersive virtual reality as a powerful adjunctive pain control technique. Patients’ subjective ratings of pain during a variety of painful medical procedures have been shown to drop B40–50% when patients are distracted by immersive virtual reality [1]. Virtual reality analgesia may work via an attentional mechanism [1]. Pain requires conscious attention [2]. The more intense the patient’s illusion of being drawn into the virtual environment (i.e. subjective presence), the more attention drawn into virtual reality, and the less pain patients experience. Although there is growing evidence that immersive virtual reality can lead to large reductions in the subjective experience of pain, there is currently no published evidence about the neural correlates of virtual reality analgesia in the brain. In the current study, we investigated the direct modulation of human brain pain responses by virtual reality distraction. In a previous unpublished study of 16 volunteers, we used a laboratory thermal pain paradigm to elicit pain- evoked brain activity (noxious pain on/off every 30 s over a 6 min period). Consistent with previous neuroimaging studies [3–5], we found thermal pain-evoked brain activity in the anterior cingulate cortex (ACC), primary (SS1) and secondary (SS2) somatosensory cortices, the insula, and thalamus, and subjects showed no habituation to the thermal pain stimuli over the 6 min scans (no difference in pain-related brain activity for the first 3 min vs second 3 min). Based on this pilot work, we determined regions of interest for fMRI as well as the thermal pain stimulation paradigm adopted in the present study. Functional imaging studies (PET and fMRI) provide evidence for attention/distraction-related reduction of pain activity in the ACC, SS1, and SS2 [6–9]. Hypnotic analgesia has also been associated with reductions in pain-related brain activity. In a study by Rainville et al. [4] subjects received hypnotic suggestions that thermal pain stimuli would feel less unpleasant. This specific manipulation produced significant drops in subjective ratings of pain unpleasantness, but no change in subjective ratings of pain intensity (ratings of worst pain). As predicted, subjects’ ratings of pain unpleasantness were positively correlated with activity in the caudal ACC implicating the involvement of the ACC in the affective dimension of pain. In another study, researchers were able to manipulate subjective ratings of pain intensity, the sensory component of pain, reducing pain-related brain activity in the SS1 cortex [6], implicating SS1 in the perception of the sensory component of pain. Because virtual reality analgesia typically reduces sub- jective ratings of both pain unpleasantness (emotional component of pain) and pain intensity (the sensory component of pain), as well as amount of time spent thinking about pain, we predicted that virtual reality would reduce pain in both the ACC and the SS1, as well as the other three brain regions of interest. Such findings might contribute to an initial understanding of the mechanisms underlying virtual reality analgesia in humans. SOMATOSENSORY SYSTEMS, PAIN NEUROREPORT 0959-4965  c Lippincott Williams & Wilkins Vol 15 No 8 7 June 2004 1245 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.