CNS Spectr. 2006;11(1):45-51

Abstract

Excessive pain during medical procedures, such as burn wound dressing changes, is a widespread medical problem and is especially challenging for children. This article describes the rationale behind virtual reality (VR) pain distraction, a new non-pharmacologic adjunctive analgesia, and gives a brief summary of empirical studies exploring whether VR reduces clinical procedural pain. Results indicate that patients using VR during painful medical procedures report large reductions in subjective pain. A neuroimaging study measuring the neural correlates of VR analgesia is described in detail. This functional magnetic resonance imaging pain study in healthy volunteers shows that the large drops in subjective pain ratings during VR are accompanied by large drops in pain-related brain activity. Together the clinical and laboratory studies provide converging evidence that VR distraction is a promising new non-pharmacologic pain control technique.

Introduction

Excessive pain during medical procedures, such as burn wound dressing changes, is a widespread medical problem. Burn pain control is especially challenging for children. Although morphine and morphine-related (ie, opioid) pain medications have been the dominant analgesic for over 100 years, patients vary in how effectively opioids reduce their pain. Most patients with severe burns report severe to excruciating pain during daily wound care despite use of opioid pain medications.¹ Opioid side effects, such as nausea and constipation, discourage the use of larger doses.² Doctors and nurses are often reluctant to prescribe and administer large doses of opioids to children out of concern for serious side effects, which include respiratory depression.³ Diversion of such opioid medications for non-medical uses (eg, recreational abuse of prescription opioids) is also a growing concern furthering pressure to find new non-pharmacologic techniques to help manage pain.

Immersive virtual reality (VR) distraction, an adjunctive psychological pain control technique, has demonstrated utility in the management of acute pain.^5,6 Preliminary evidence suggests this intervention can be quite powerful. For example, preliminary clinical results from a case study (N=2) suggest that VR can reduce pain more effectively than distraction with a two-dimensional video game.⁷ Burn patients’ subjective pain ratings during wound care and physical therapy sessions have consistently shown clinically meaningful (ie, >30%) reductions when patients are distracted by immersive VR^7-10 Furthermore, preliminary evidence⁶ suggests that VR distraction works even during the most painful portions of wound care procedures conducted in the scrubtank.

SnowWorld

SnowWorld was the first immersive VR software specifically designed for the treatment of pain (Figures 1 and 2). In light of reports from patients that they tend to think about their original burn event during wound care,¹¹ SnowWorld portrays an icy, cool virtual environment that directly contrasts the “hot” scenarios and unpleasant memories that are usually associated with burn injuries. Immersive VR technology systems consist of a VR helmet that positions miniature liquid crystal displays ~1 inch in front of the user’s eyes, blocks the user’s view of the real world, and presents patients with a view of a computer-generated world. An electromagnetic head-tracking system sends the x-y-z coordinates of the user’s head orientation to the VR computer (x=left and right translations/movements, y=up and down movements, z=forward and backward movements). The computer uses this information to track gaze direction. What the user sees in VR changes as he/she looks around the virtual world. For example, if patients look up, they see the sky; if they look down, they see an icy animated river; if they look straight ahead, they see sky, river, and icy canyon walls. In SnowWorld, patients interact with the three-dimensional (3-D) computer-generated world by looking around and shooting snowballs at snowmen, igloos, robots, and penguins using a simple human-computer interface—aiming via gaze direction and shooting by pressing the spacebar on a computer keyboard. Snowballs splash into the river or explode with 3-D sound effects. When hit by a well-aimed snowball, snowmen disappear into a puff and virtual penguins turn upside down. The patient’s ability to interact with the virtual objects in SnowWorld—the 3-D sound effects and special effects, and the fact that the patient’s real world view of their medical procedure is blocked—all contribute to the patient’s illusion of going inside the 3-D computer-generated world and to their conscious perception of a reduction of the pain experience. In addition, Hoffman and colleagues⁶ have developed innovative new VR head-mounted displays, such as the fiberoptic water-friendly VR helmet (Figure 3), to deliver SnowWorld to adult and pediatric burn patients during their wound care in a scrub tank (a sterile tub of water used to help loosen and remove their bandages and clean their wounds).

Functional Neuroimaging

The analgesic mechanism of VR seems related to the fact that, to varying degrees, the patient’s limited attentional resources are drawn into SnowWorld and away from the pain experience, while their bodies are being physically manipulated in the real world. When they go into VR during burn wound care, patients commonly report significantly less pain, with little or no side effects.^6-9 Simulator sickness, a form of motion sickness, has not been a problem with SnowWorld, in large part because SnowWorld was specifically designed to minimize simulator sickness. Furthermore, the use of high resolution VR helmets, high-quality VR equipment minimizes artifacts (eg, delays between when patients turns their head and when the scene changes). Patients with a history of extreme motion sickness (~5% of the population) are excluded. Thus, unlike with opioids, whose side effects (drowsiness, loss of appetite, and lethargy) can affect patients for hours after administration, VR users show few or no side effects from engaging in SnowWorld. In fact, patients often report having “mild fun” during their burn care when in VR (compared with “no fun” during burn care with only pharmacologic analgesics).

Functional neuroimaging, both using positron emission tomography and functional magnetic resonance imaging (fMRI), has been used extensively to identify specific anatomic brain regions that are metabolically active during pain stimulation.^16,19,20,22 Although there are some variations between studies, five anatomic brain regions have been consistently identified as key brain activation sites when subjects experience acute pain-: the anterior cingulate cortex (ACC), the insula, the thalamus, and the primary and secondary somatosensory cortices (SS1,¹² SS2). These five areas are sometimes collectively referred to as the “pain matrix.” Recent neuroimaging studies have begun to explore the brain’s response to pharmacologic^13,14 and non-pharmacologic^15,16 analgesic interventions. Pharmacologic treatment of volunteers subjected to experimental pain has shown consistent changes in specific regions of the pain matrix. For example, subanesthetic levels of ketamine reduced pain scores coincident with reduced pain-related brain activation in the insula and thalamus.¹³ Similarly, another clinically effective opioid analgesic yields similar results: Remifentanil is associated with decreased pain activation in the insula and ACC.¹⁴ Parallel research has demonstrated that non-pharmacologic, cognitive modulation of pain via attentional distraction is also associated with specific regional reductions in metabolic brain activity, as reviewed by Porro.¹⁵ One particularly relevant example involved a counting Stroop task.¹⁶ Subjects saw between one and four identical words presented on the screen as a vertical list. This list would change about once per second. Patients were to indicate the number of words presented on the screen (regardless of what the words said) as quickly and accurately as possible, with strong emphasis on not sacrificing accuracy for speed. In the interference condition, the identical words were the names of numbers (one, two, three, or four), so participants had to ignore what the words said in order to correctly indicate how many words were presented. Attentional distraction via a counting Stroop task reduced subjective pain ratings, and fMRI showed reductions in pain-related brain activity in the thalamus, insula, and the cognitive portion of the ACC, supporting the behavioral results of reduced pain perception.¹⁶ Furthermore, Derbyshire and colleagues¹⁷ and Nakata and colleagues¹⁸ have shown that motor activity is associated with the modulation of subjective pain and related brain activation, particularly in SS1 and SS2.^17,18 Together, these reports suggest that a behavioral intervention that includes both attentional and motor demands, such as VR, may have a beneficial analgesic effect.

Pain-Related Brain Activity During Virtual Reality in Healthy Volunteers

Research with healthy normal volunteers has also demonstrated that hypnotic analgesia is associated with reductions in pain-related brain activity.¹⁹ The nature of the hypnotic suggestion influences the characteristics of the pain reported by participants, and simultaneously influences the parts of the brain that show reductions in activity.¹⁹ When highly hypnotizable subjects were given instructions to feel less pain during thermal stimulations, they reported a reduction in pain unpleasantness ratings, and showed an associated reduction in pain-related brain activity in the ACC,¹⁹ consistent with the notion that the ACC is an area of the brain important for processing emotional aspects of pain. In a second study,²⁰ when highly hypnotizable participants were given posthypnotic suggestions that they would feel a reduction in pain intensity, subjects reported lower pain intensity and an associated reduction in pain-related brain activity in the primary somatosensory cortex,²⁰ supporting the notion that the primary somatosensory cortex is an area of the brain important for processing pain intensity.

Because VR distraction leads to unusually large reductions in subjective pain ratings of pain intensity, pain unpleasantness, and amount of time spent thinking about pain, we hypothesized²² that VR would reduce pain-related brain activity (as assessed by fMRI) in all five brain regions of interest, including the ACC, SS1, SS2, insula, and thalamus, when participants received immersive VR distraction. Functional neuroimaging with fMRI assesses brain metabolic activity by measuring changes in the blood oxygen level-dependent signal when local cerebral blood flow increases in response to an increased regional cellular metabolic demand. Although fMRI poses technical challenges imposed by strong magnetic fields (eg, no metallic objects are allowed within or near the scanner), it offers the benefit of no ionized radiation exposure to either subjects or investigators and several other advantages. In collaboration with the University of Washington Department of Radiology, Hoffman and colleagues²¹ developed a fiberoptic, magnet-friendly, “photonic” VR helmet (Figure 4) that delivers SnowWorld to healthy volunteers experiencing safe and tolerable experimental pain while undergoing fMRI, to explore the neural correlates of pain modulation with VR.²²

In a within-subject study utilizing this “magnet-friendly” VR delivery system, Hoffman and colleagues²² recorded regional brain activity in healthy volunteers who received brief, tolerable, and safe thermal pain stimulations (on/off every 30 seconds) both with and without immersive VR distraction (Figure 5). Functional brain imaging was performed with simultaneous VR distraction and thermal stimulation of the dorsal foot. Healthy normal volunteers received six 30-second thermal pain stimuli during an fMRI brain scan. The temperature used was individually determined for each participant prior to the scan using the psychophysical method of ascending levels. They started with a low temperature for 30 seconds and collected subjective pain ratings. With the subjects’ permission, the researchers then slightly increased the temperature until the subject identified the temperature as “painful but tolerable.” The thermal temperature approved by the subject was used during their fMRI scan. They received the thermal pain stimulus “off” for 30 seconds (lukewarm) and “on” for 30 seconds (painful but tolerable) six times during an fMRI scan (three 30-second pain stimuli in VR, 3 seconds with no VR [Figure 5]). Participants went into SnowWorld, a 3-D icy canyon, and shot snowballs at snowmen, igloos, and robots during half of their scan (3.5 minutes), to see if VR distraction reduced their subjective pain ratings, and to measure if VR reduced the amount of pain-related brain activity. During the other half of the scan (3.5 minutes), patients looked at a static, black fixation cross against a white background and heard no sound effects. The treatment order was randomized such that subjects were approximately equally likely to receive 3.5 minutes of VR before or after the 3.5-minute fixation cross. Subjects could stop the study at any time. Informed written consent was obtained from each participant prior to the study using a protocol reviewed and approved by the University of Washington institutional review board.

Changes in the amount of pain-related brain activity during VR were first calculated by comparing VR + pain versus VR + no pain. Changes in the amount of pain-related brain activity during no VR were then calculated by comparing (no VR + pain) versus (no VR + no pain).

This allowed researchers²² to separately calculate the amount of pain-related brain activity during VR, and the amount of pain-related brain activity during No VR. In other words, the amount of pain-related brain activity resulting from the pain-on/pain-off manipulation was abstracted from the data (calculated separately for each distraction treatment condition), and only then was the amount of pain-related brain activity during the two distraction treatment conditions (VR versus no VR) compared.

Using a general linear, fixed effects model and z-transforms (adjusted for motion and temporal Gaussian smoothing), a cluster analysis was performed on the results, producing a P-value for each cluster. This value was represented graphically as an average for all subjects on the structural anatomic map (Figure 6). The first finding²² was that with no VR, subjects consistently showed significant pain-related brain activity in all five regions of the pain matrix (ACC, insula, thalamus, SS1, and SS2), a finding consistent with previous reports of functional neural imaging (positron emission tomography and fMRI) during thermal pain stimulation. Second, and as predicted, significant reductions in pain-related brain activity were observed in all five regions of interest when subjects went into SnowWorld²² (Figure 6), conservatively corrected for multiple comparisons at P<.002. Furthermore, the reductions in pain-related brain activity with VR specifically accompanied the reductions in participants’ subjective reports of their sensory, cognitive, and emotional pain experience. For the group studied, VR reduced subjects’ reports of “worst pain” (sensory component of pain) by 30%, “time spent thinking about pain” (cognitive component of pain) by 44%, and “pain unpleasantness” (emotional component of pain) by 45%.²²

Conclusion

In addition to reducing the amount of pain people consciously report feeling, VR distraction appears to modify how the brain processes incoming signals from pain receptors.²² These fMRI results provide converging physiological evidence that VR reduces the pain experience by modulating the brain’s response to peripheral painful stimulation, modulating both sensory and emotional aspects of pain processing. In addition to the traditional nerve pathways from pain receptors to the brain via the spinal cord, Melzack³ and Melzack and Wall⁴ have postulated the existence of neural pathways that carry signals from the brain to the dorsal horn of the spinal cord (ie, descending modulatory pathways). Where in the central nervous system (eg, spinal cord, brainstem, or cortex) this modulation occurs, however, is currently unknown although in our study, the resulting decrease in pain-related brain activity can be observed in the five regions of interest of the pain matrix, and these regions are located in both the brainstem and cortex. In other words, Hoffman and colleagues²² cannot determine how far down in the central nervous system the modulation of nociception occurs.

Regardless of the mechanism of VR analgesia, because excessive pain is such a widespread problem with adults and children during a wide range of medical procedures, and in light of the encouraging preliminary empirical results in both clinical and experimental pain, additional research exploring the use of immersive VR for distracting patients during painful procedures is warranted. Recent research (H.G. Hoffman, PhD, et al, data not yet published, 2006) found that increasing the quality of the VR helmet visual display can substantially enhance the analgesic effectiveness of VR.

High-tech VR helmets are currently expensive; this is a limiting factor. For example, the 1280 VR, a new helmet with similar specifications to the one used by Hoffman and colleagues²⁴ costs ~$16,000 at www.imprintit.com and is relatively heavy (<2 lb), Another more effective helmet, the Kaiser SR-80, is available for $32,000 at http://www.rockwellcollins.com. New display technologies are slated to emerge in the next 2–3 years. These will reduce the costs and further improve the quality and weight of high-tech VR helmets.⁵ Six major medical centers in the United States are either using or making preparations to utilize high-tech VR helmets with SnowWorld for pain control, and through charitable donations, SnowWorld is provided free of charge to eligible medical centers to help mitigate costs.

Although SnowWorld VR distraction appears to be most appropriate for procedural pain^23-25 the number of painful medical procedures necessitating adjunctive analgesia is large and there is tremendous potential for increasing the number of patients who could benefit from emerging new pain treatments, such as VR analgesia. CNS

References

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Dr. Hoffman is director of the Virtual Reality Analgesia Research Center and affiliate faculty member in the Department of Radiology and Psychology at the University of Washington Human Interface Technology Laboratory in Seattle. Dr. Richards is professor in the Department of Radiology at the University of Washington. Mr. Bills is a graduate student at the University of Alaska in Anchorage. Dr. Van Oostrom is an anesthesiology resident at the University of Washington. Mr. Magula is an instrument maker at www.VRpain.com. Dr. Seibel is research assistant professor in the Department of Biomedical Engineering at the University of Washington and co-director of the Human Interface Technology Laboratory. Dr. Sharar is professor of anesthesiology in the Department of Anesthesiology at the University of Washington.

Disclosure: The authors do not have any affiliation or financial interest in any organization that might pose a conflict of interest.

Funding/Support: This work was supported in part by National Institute of Child Health and Development grants HD37683 and HD40954 awarded to Dr. Sharar, by National Institutes of Health grant GM42725, and by funding from the Paul Allen Family Foundation to the Harborview Burn Center in Seattle, Washington. Dr. Siebel has received support from the International Vision Foundation.

This article was submitted on August 11, 2005, and accepted on December 8, 2005.

Please direct all correspondence to: Hunter G. Hoffman, PhD, Human Interface Technology Laboratory, Box 352142, University of Washington, Seattle, WA, 98195-2142; E-mail: hunter@hitL.washington.edu.