The Analgesic Effects of Opioids and Immersive Virtual Reality Distraction: Evidence from Subjective and Functional Brain Imaging Assessments

BACKGROUND:Immersive virtual reality (VR) is a novel form of distraction analgesia, yet its effects on pain-related brain activity when used adjunctively with opioid analgesics are unknown. We used subjective pain ratings and functional magnetic resonance imaging to measure pain and pain-related brain activity in subjects receiving opioid and/or VR distraction. METHODS:Healthy subjects (n = 9) received thermal pain stimulation and were exposed to four intervention conditions in a within-subjects design: (a) control (no analgesia), (b) opioid administration [hydromorphone (4 ng/mL target plasma level)], (c) immersive VR distraction, and (d) combined opioid + VR. Outcomes included subjective pain reports (0–10 labeled graphic rating scales) and blood oxygen level-dependent assessments of brain activity in five specific, pain-related regions of interest. RESULTS:Opioid alone significantly reduced subjective pain unpleasantness ratings (P < 0.05) and significantly reduced pain-related brain activity in the insula (P < 0.05) and thalmus (P < 0.05). VR alone significantly reduced both worst pain (P < 0.01) and pain unpleasantness (P < 0.01) and significantly reduced pain-related brain activity in the insula (P < 0.05), thalmus (P < 0.05), and SS2 (P < 0.05). Combined opioid + VR reduced pain reports more effectively than did opioid alone on all subjective pain measures (P < 0.01). Patterns of pain-related blood oxygen level-dependent activity were consistent with subjective analgesic reports. CONCLUSIONS:These subjective pain reports and objective functional magnetic resonance imaging results demonstrate converging evidence for the analgesic efficacy of opioid administration alone and VR distraction alone. Furthermore, patterns of pain-related brain activity support the significant subjective analgesic effects of VR distraction when used as an adjunct to opioid analgesia. These results provide preliminary data to support the clinical use of multimodal (e.g., combined pharmacologic and nonpharmacologic) analgesic techniques.

[1]  M. Bushnell,et al.  Pain perception: is there a role for primary somatosensory cortex? , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[2]  S. Archer,et al.  Pharmacokinetics and Bioavailability of Single-Dose Intranasal Hydromorphone Hydrochloride in Healthy Volunteers , 2003, Anesthesia and analgesia.

[3]  Bruce H. Thomas,et al.  Virtual Reality as a Pediatric Pain Modulation Technique: A Case Study , 2003, Cyberpsychology Behav. Soc. Netw..

[4]  S. Clare,et al.  Imaging how attention modulates pain in humans using functional MRI. , 2002, Brain : a journal of neurology.

[5]  M. Bushnell,et al.  Pain affect encoded in human anterior cingulate but not somatosensory cortex. , 1997, Science.

[6]  Richard G. Wise,et al.  Combining fMRI with a Pharmacokinetic Model to Determine Which Brain Areas Activated by Painful Stimulation Are Specifically Modulated by Remifentanil , 2002, NeuroImage.

[7]  Stephen M. Smith,et al.  A global optimisation method for robust affine registration of brain images , 2001, Medical Image Anal..

[8]  C. Chapman,et al.  Hydromorphone analgesia after intravenous bolus administration , 1997, Pain.

[9]  M. Bushnell,et al.  Cortical representation of the sensory dimension of pain. , 2001, Journal of neurophysiology.

[10]  B. Thomas,et al.  The efficacy of playing a virtual reality game in modulating pain for children with acute burn injuries: A randomized controlled trial [ISRCTN87413556] , 2005, BMC pediatrics.

[11]  Tapabrata Maiti,et al.  Analysis of Longitudinal Data (2nd ed.) (Book) , 2004 .

[12]  Stephen M. Smith,et al.  Temporal Autocorrelation in Univariate Linear Modeling of FMRI Data , 2001, NeuroImage.

[13]  G. Marshall Attention and Will , 1970 .

[14]  B. Coda,et al.  Multiple‐Dose Evaluation of Intravenous Hydromorphone Pharmacokinetics in Normal Human Subjects , 1991, Anesthesia and analgesia.

[15]  Eric J. Seibel,et al.  Using fMRI to Study the Neural Correlates of Virtual Reality Analgesia , 2006, CNS Spectrums.

[16]  H. Hoffman,et al.  Effectiveness of Virtual Reality–Based Pain Control With Multiple Treatments , 2001, The Clinical journal of pain.

[17]  P. Diggle Analysis of Longitudinal Data , 1995 .

[18]  Azucena García-Palacios,et al.  Immersive Virtual Reality for Reducing Experimental Ischemic Pain , 2003, Int. J. Hum. Comput. Interact..

[19]  Hunter G Hoffman,et al.  Water-friendly virtual reality pain control during wound care. , 2004, Journal of clinical psychology.

[20]  Dennis C. Turk,et al.  The utility of cognitive coping strategies for altering pain perception: a meta-analysis , 1989, Pain.

[21]  Robert C. Coghill,et al.  Neural correlates of interindividual differences in the subjective experience of pain , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Richard Rogers,et al.  An Investigation to Dissociate the Analgesic and Anesthetic Properties of Ketamine Using Functional Magnetic Resonance Imaging , 2004, Anesthesiology.

[23]  Hunter G. Hoffman,et al.  Modulation of thermal pain-related brain activity with virtual reality: evidence from fMRI , 2004, Neuroreport.

[24]  H. Hoffman,et al.  Use of virtual reality for adjunctive treatment of adult burn pain during physical therapy: a controlled study. , 2000, The Clinical journal of pain.

[25]  Irene Tracey,et al.  Using fMRI to Quantify the Time Dependence of Remifentanil Analgesia in the Human Brain , 2004, Neuropsychopharmacology.

[26]  Hunter G. Hoffman,et al.  The Illusion of Presence in Immersive Virtual Reality during an fMRI Brain Scan , 2003, Cyberpsychology Behav. Soc. Netw..

[27]  M. Jensen,et al.  The validity and reliability of pain measures in adults with cancer. , 2003, The journal of pain : official journal of the American Pain Society.

[28]  Alan C. Evans,et al.  A Three-Dimensional Statistical Analysis for CBF Activation Studies in Human Brain , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[29]  Robert M Sweet,et al.  Virtual reality as an adjunctive pain control during transurethral microwave thermotherapy. , 2005, Urology.

[30]  L. Jacoby,et al.  Becoming famous without being recognized: Unconscious influences of memory produced by dividing attention , 1989 .

[31]  Attention and pain: merging behavioural and neuroscience investigations , 2005, Pain.

[32]  T. Furness,et al.  Virtual reality as an adjunctive pain control during burn wound care in adolescent patients , 2000, Pain.

[33]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[34]  Mark W. Woolrich,et al.  Multilevel linear modelling for FMRI group analysis using Bayesian inference , 2004, NeuroImage.

[35]  Stephen M. Smith,et al.  General multilevel linear modeling for group analysis in FMRI , 2003, NeuroImage.

[36]  Hunter G. Hoffman,et al.  Manipulating presence influences the magnitude of virtual reality analgesia , 2004, Pain.

[37]  Jonathan L Wright,et al.  Renal artery pseudoaneurysm after laparoscopic partial nephrectomy. , 2005, Urology.

[38]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[39]  D. Sessler,et al.  Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine , 2005, Anesthesiology.