Abstract
Recurrent use of prescription opioid analgesics by chronic pain patients may result in opioid dependence, which involves implicit neurocognitive operations that organize and impel craving states and compulsive drug taking behavior. Prior studies have identified an attentional bias (AB) towards heroin among heroin dependent individuals. The aim of this study was to determine whether opioid-dependent chronic pain patients exhibit an AB towards prescription opioid-related cues. Opioid-dependent chronic pain patients (n = 32) and a comparison group of non-dependent opioid users with chronic pain (n = 33) completed a dot probe task designed to measure opioid AB. Participants also rated their opioid craving and self-reported arousal associated with opioid-related and neutral images, pain severity, and relief from pain treatments. Repeated-measures ANOVA revealed a significant group (opioid-dependent vs. non-dependent opioid user) × presentation duration (200. vs. 2,000 ms.) interaction, such that opioid-dependent individuals evidenced a significant AB towards opioid cues presented for 200 ms but not for cues presented for 2,000 ms, whereas non-dependent opioid users did not exhibit a significant mean AB at either stimulus duration. Among opioid-dependent individuals, 200 ms opioid AB was significantly associated with opioid craving, while among non-dependent opioid users, 200 ms opioid AB was significantly associated with relief from pain treatments. Furthermore, dependent and non-dependent opioid users experienced opioid cues as significantly more arousing than neutral cues. Opioid dependence among chronic pain patients appears to involve an automatic AB towards opioid-related cues. When coupled with chronic pain, attentional fixation on opioid cues may promote compulsive drug use and addictive behavior.
This is a preview of subscription content, access via your institution.

References
American Pain Society. (2002). Decade of pain report. Retrieved February 2, 2012, from http://www.ampainsoc.org/pub/bulletin/jul02/pres.html
Andreassi, J. L. (2000) Psychophysiology human behavior and physiological response (4th ed.). Mahwah, NJ: L. Erlbaum, Publishers.
Baker, T. B., Piper, M. E., McCarthy, D. E., Majeski, M. R., & Fiore, M. C. (2004). Addiction motivation reformulated: An affective processing model of negative reinforcement. Psychological Review, 111, 35–51.
Baliki, M. N., Geha, P. Y., Fields, H. L., & Apkarian, A. V. (2010). Predicting value of pain and analgesia: Nucleus accumbens response to noxious stimuli changes in the presence of chronic pain. Neuron, 66, 149–160.
Bearre, L., Sturt, P., Bruce, G., & Jones, B. T. (2007). Heroin-related attentional bias and monthly frequency of heroin use are positively associated in attenders of a harm reduction service. Addictive Behaviors, 32, 784–792.
Butler, S. F., Budman, S. H., Fernandez, K. C., Houle, B., Benoit, C., Katz, N., et al. (2007). Development and validation of the current opioid misuse measure. Pain, 130, 144–156.
Chou, R., Fanciullo, G. J., Fine, P. G., Adler, J. A., Ballantyne, J. C., Davies, P., et al. (2009). Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. The Journal of Pain, 10, 113–130.
Chu, L. F., Angst, M. S., & Clark, D. (2008). Opioid-induced hyperalgesia in humans: Molecular mechanisms and clinical considerations. Clinical Journal of Pain, 24, 479–496.
Constantinou, N., Morgan, C. J., Battistella, S., O’Ryan, D., Davis, P., & Curran, H. V. (2010). Attentional bias, inhibitory control and acute stress in current and former opiate addicts. Drug and Alcohol Dependence, 109, 220–225.
Denisco, R. A., Chandler, R. K., & Compton, W. M. (2008). Addressing the intersecting problems of opioid misuse and chronic pain treatment. Experimental and Clinical Psychopharmacology, 16, 417–428.
Duncan, J., Ward, R., & Shapiro, K. (1994). Direct measurement of attentional dwell time in human vision. Nature, 369, 313–315.
Field, M., & Cox, W. M. (2008). Attentional bias in addictive behaviors: A review of its development, causes, and consequences. Drug and Alcohol Dependence, 97, 1–20.
Field, M., Mogg, K., Zetteler, J., & Bradley, B. P. (2004). Attentional biases for alcohol cues in heavy and light social drinkers: The roles of initial orienting and maintained attention. Psychopharmacology (Berl), 176, 88–93.
Field, M., Munafo, M. R., & Franken, I. H. (2009). A meta-analytic investigation of the relationship between attentional bias and subjective craving in substance abuse. Psychological Bulletin, 135, 589–607.
Fields, H. (2004). State dependent opioid control of pain. Nature Reviews Neuroscience, 5, 565–575.
Filion, D. L., Dawson, M. E., & Schell, A. M. (1993). Modification of the acoustic startle-reflex eyeblink—a tool for investigating early and late attentional processes. Biological Psychology, 35, 185–200.
Franken, I. H. (2003). Drug craving and addiction: Integrating psychological and neuropsychopharmacological approaches. Progress in Neuropsychopharmacology and Biological Psychiatry, 27, 563–579.
Franken, I. H., Hendriksa, V. M., & van den Brink, W. (2002). Initial validation of two opiate craving questionnaires: The obsessive compulsive drug use scale and the desires for drug questionnaire. Addictive Behaviors, 27, 675–685.
Franken, I. H., Kroon, L. Y., Wiers, R. W., & Jansen, A. (2000). Selective cognitive processing of drug cues in heroin dependence. Journal of Psychopharmacology, 14, 395.
Froeliger, B., Modlin, L. A., Kozink, R. V., Wang, L., & McClernon, F. J. (2012a). Smoking abstinence and depressive symptoms modulate the executive control system during emotional information processing. Addiction Biology, 17, 668–679.
Froeliger, B., Modlin, L., Wang, L., Kozink, R. V., & McClernon, F. J. (2012b). Nicotine withdrawal modulates frontal brain function during an affective Stroop task. Psychopharmacology (Berl), 220, 707–718.
Garavan, H., Kaufman, J. N., & Hester, R. (2008). Acute effects of cocaine on the neurobiology of cognitive control. Philosophical Transactions of the Royal Society B: Biological Sciences, 363, 3267–3276.
Garland, E. L. (2011). Trait mindfulness predicts attentional and autonomic regulation of alcohol cue-reactivity. Journal of Psychophysiology, 25, 180–189.
Garland, E. L. (2012). Pain processing in the human nervous system: A selective review of nociceptive and biobehavioral pathways. Primary Care: Clinics in Office Practice. doi:10.1016/j.pop.2012.06.013.
Garland, E. L., Boettiger, C. A., & Howard, M. O. (2011). Targeting cognitive-affective risk mechanisms in stress-precipitated alcohol dependence: An integrated, biopsychosocial model of allostasis, automaticity, and addiction. Medical Hypotheses, 76, 745–754.
Garland, E. L., Franken, I. H., & Howard, M. O. (2012). Cue-elicited heart rate variability and attentional bias predict alcohol relapse following treatment. Psychopharmacology, 222, 17–26.
Garland, E. L., Gaylord, S. A., Boettiger, C. A., & Howard, M. O. (2010). Mindfulness training modifies cognitive, affective, and physiological mechanisms implicated in alcohol dependence: Results of a randomized controlled pilot trial. Journal of Psychoactive Drugs, 42, 177–192.
Green, T. C., Black, R., Grimes Serrano, J. M., Budman, S. H., & Butler, S. F. (2011). Typologies of prescription opioid use in a large sample of adults assessed for substance abuse treatment. PLoS ONE, 6, e27244.
Ives, T. J., Chelminski, P. R., Hammett-Stabler, C. A., Malone, R. M., Perhac, J. S., Potisek, N. M., et al. (2006). Predictors of opioid misuse in patients with chronic pain: A prospective cohort study. BMC Health Services Research, 6, 46.
Kilpatrick, L., & Cahill, L. (2003). Amygdala modulation of parahippocampal and frontal regions during emotionally influenced memory storage. Neuroimage, 20, 2091–2099.
Koob, G. F., & Volkow, N. D. (2009). Neurocircuitry of addiction. Neuropsychopharmacology, 35, 217–238.
Korff, M. V., Saunders, K., Thomas Ray, G., Boudreau, D., Campbell, C., Merrill, J., et al. (2008). De facto long-term opioid therapy for noncancer pain. The Clinical Journal of Pain, 24, 521.
Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (1997). International affective picture system (IAPS): Instruction manual and affective ratings. Technical report A-4. The Center for Research in Psychophysiology, University of Florida.
Laurrauri, J. A., & Schmajuk, N. A. (2008). Attentional, associative, and configural mechanisms in extinction. Psychological Review, 115, 640–676.
LeDoux, J. E. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23, 155–184.
Lubman, D. I., Peters, L. A., Mogg, K., Bradley, B. P., & Deakin, J. F. (2000). Attentional bias for drug cues in opiate dependence. Psychological Medicine, 30, 169–175.
Marissen, M. A., Franken, I. H., Waters, A. J., Blanken, P., van den Brink, W., & Hendriks, V. M. (2006). Attentional bias predicts heroin relapse following treatment. Addiction, 101, 1306–1312.
O’Brien, C. P., Childress, A. R., Ehrman, R., & Robbins, S. J. (1998). Conditioning factors in drug abuse: Can they explain compulsion? Journal of Psychopharmacology, 12, 15.
Passik, S. D. (2009). Issues in long-term opioid therapy: Unmet needs, risks, and solutions. Mayo Clinic Proceedings, 84, 593–601.
Pavlov, I. P. (1927). Conditioned reflexes. Oxford: Oxford University Press.
Pearce, J. M., & Bouton, M. E. (2001). Theories of associative learning in animals. Annual Review of Psychology, 52, 111–139.
Pearce, J. M., & Hall, G. (1980). A model for Pavlovian learning: Variations in the effectiveness of conditioned but not of unconditioned stimuli. Psychological Review, 87, 532–552.
Pierce, R. C., & Vanderschuren, L. (2010). Kicking the habit: The neural basis of ingrained behaviors in cocaine addiction. Neuroscience and Biobehavioral Reviews, 35, 212–219.
Ratcliff, R. (1993). Methods of dealing with reaction time outliers. Psychological Bulletin, 114, 510–532.
Robinson, T. E., & Berridge, K. C. (2001). Incentive-sensitization and addiction. Addiction, 96, 103–114.
Robinson, T. E., & Berridge, K. C. (2008). The incentive sensitization theory of addiction: Some current issues. Philosophical Transactions of the Royal Society of London B Biological Sciences, 363, 3137–3146.
Sheehan, D. V., Lecrubier, Y., Sheehan, K. H., Amorim, P., Janavs, J., Weiller, E., et al. (1998). The mini-international neuropsychiatric interview (M I N I): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry, 59, 22–33.
Stacy, A. W., & Wiers, R. W. (2010). Implicit cognition and addiction: A tool for explaining paradoxical behavior. Annual Review of Clinical Psychology, 6, 551–575.
Sullivan, M. D., Edlund, M. J., Fan, M. Y., Devries, A., Brennan Braden, J., & Martin, B. C. (2010). Risks for possible and probable opioid misuse among recipients of chronic opioid therapy in commercial and Medicaid insurance plans: The TROUP Study. Pain, 150, 332–339.
Theeuwes, J. (2005). Irrelevant singletons capture attention. Neurobiology of Attention (pp. 418–424). London: Elsevier Academic Press.
Tiffany, S. T. (1990). A cognitive model of drug urges and drug-use behavior: Role of automatic and nonautomatic processes. Psychological Review, 97, 147–168.
Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Logan, J., Childress, A. R., et al. (2008). Dopamine increases in striatum do not elicit craving in cocaine abusers unless they are coupled with cocaine cues. NeuroImage, 39, 1266–1273.
Vollstädt-Klein, S., Loeber, S., Richter, A., Kirsch, M., Bach, P., von der Goltz, C., et al. (2011). Validating incentive salience with functional magnetic resonance imaging: Association between mesolimbic cue reactivity and attentional bias in alcohol-dependent patients. Addiction Biology,. doi:10.1111/j.1369-1600.2011.00352.x
Wasan, A. D., Butler, S. F., Budman, S. H., Fernandez, K., Weiss, R. D., Greenfield, S. F., et al. (2009). Does report of craving opioid medication predict aberrant drug behavior among chronic pain patients? Clinical Journal of Pain, 25, 193–198.
Wasan, A. D., Ross, E. L., Michna, E., Chibnik, L., Greenfield, S. F., Weiss, R. D., et al. (2012). Craving for prescription opioids in patients with chronic pain: A longitudinal outcomes trial. The Journal of Pain, 13, 146–154.
Waters, A. J., Marhe, R., & Franken, H. A. (2012). Attentional bias to drug cues is elevated before and during temptations to use heroin in cocaine. Psychopharmacology (Berl), 219, 909–921.
Wilson, J. F. (2007). Strategies to stop abuse of prescribed opioid drugs. Annals of Internal Medicine, 146, 897–900.
Wolf, M. E. (2002). Addiction: Making the connection between behavioral changes and neuronal plasticity in specific pathways. Molecular Interventions, 2, 146–157.
Yang, Z., Xie, J., Shao, Y.-C., Xie, C.-M., Fu, L.-P., Li, D.-J., et al. (2009). Dynamic neural responses to cue-reactivity paradigms in heroin-dependent users: An fMRI study. Human Brain Mapping, 30, 766–775.
Zacny, J., Bigelow, G., Compton, P., Foley, K., Iguchi, M., & Sannerud, C. (2003). College on problems of drug dependence taskforce on prescription opioid non-medical use and abuse: Position statement. Drug and Alcohol Dependence, 69, 215–232.
Zijlstra, F., Veltman, D. J., Booij, J., van den Brink, W., & Franken, I. H. A. (2009). Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males. Drug and Alcohol Dependence, 99, 183–192.
Acknowledgments
The first author (E.L.G.) was supported in developing this manuscript by Grant Number DA032517 from the National Institute of Drug Abuse, a grant from the Fahs Beck Fund for Research and Experimentation, and a grant from the Florida State University Council on Research and Creativity. We would like to thank Jaclyn Williams, Olivia Garrison, Susan Howell, and Hillary Gale for their assistance in data collection and data entry.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Garland, E.L., Froeliger, B.E., Passik, S.D. et al. Attentional bias for prescription opioid cues among opioid dependent chronic pain patients. J Behav Med 36, 611–620 (2013). https://doi.org/10.1007/s10865-012-9455-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10865-012-9455-8
Keywords
- Opioid addiction
- Opioid dependence
- Craving
- Attentional bias
- Chronic pain
- Implicit cognition
- Opiate