Chronic Pain and Opioids



Opioid analgesics have long been accepted by the medical community for the treatment of acute, surgical and cancer-related pain; only recently have opioids become more widely used in the treatment of chronic pain conditions. Studies have demonstrated that opioids can be effective in the treatment of chronic pain in some individuals. However, there are certain risks associated with the long-term use of opioid analgesics. The prescribing clinician must consider not only common side effect profile of these medications, but also the unique side effects associated with long-term opioid administration and the risk of addiction. The risks and benefits of prescribing opioids must be carefully weighed for each chronic pain patient. The following chapter provides a discussion of the risks and benefits of using opioid analgesics in the treatment of chronic pain. Potential problems associated with opioid therapy are addressed, and various strategies to manage these problems are also included.


Opioid Receptor Opioid Analgesic Opioid Dependence Opioid Therapy Urine Drug Screen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abs, R., Verhelst, J., Maeyaert, J., Van Buyten, J. P., Opsomer, F., et al. (2000). Endocrine consequences of long-term intrathecal administration of opioids. The Journal of Clinical Endocrinology and Metabolism, 85, 2215–2222.PubMedCrossRefGoogle Scholar
  2. Amabile, C. M., & Bowman, B. J. (2006). Overview of oral modified-release opioid products for the management of chronic pain. The Annals of Pharmacotherapy, 40, 1327–1335.PubMedCrossRefGoogle Scholar
  3. American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders. Washington, DC: American Psychiatric Association.Google Scholar
  4. American Psychiatric Association. (2011). DSM-5 development proposed revisions: Substance-related disorders. Washington, DC: American Psychiatric Association.Google Scholar
  5. Apkarian, A. V., Sosa, Y., Sonty, S., Levy, R. M., Harden, R. N., et al. (2004). Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. The Journal of Neuroscience, 24, 10410–10415.PubMedCrossRefGoogle Scholar
  6. Arner, S., & Meyerson, B. A. (1988). Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain, 33, 11–23.PubMedCrossRefGoogle Scholar
  7. Arnold, L. M., Hudson, J. I., Hess, E. V., Ware, A. E., Fritz, D. A., et al. (2004). Family study of fibromyalgia. Arthritis and Rheumatism, 50, 944–952.PubMedCrossRefGoogle Scholar
  8. Askitopoulou, H., Ramoutsaki, I. A., & Konsolaki, E. (2002). Archaeological evidence on the use of opium in the Minoan world. International Congress Series, 1292, 23–97.CrossRefGoogle Scholar
  9. Asmundson, G. J., Coons, M. J., Taylor, S., & Katz, J. (2002). PTSD and the experience of pain: Research and clinical implications of shared vulnerability and mutual maintenance models. Canadian Journal of Psychiatry, 47, 930–937.Google Scholar
  10. Asmundson, G. J., & Katz, J. (2009). Understanding the co-occurrence of anxiety disorders and chronic pain: State-of-the-art. Depression and Anxiety, 26, 888–901.PubMedCrossRefGoogle Scholar
  11. Baile, C. A., McLaughlin, C. L., & Della-Fera, M. A. (1986). Role of cholecystokinin and opioid peptides in control of food intake. Physiological Reviews, 66, 172–234.PubMedGoogle Scholar
  12. Bailey, C. J., & Flatt, P. R. (1987). Increased responsiveness to glucoregulatory effect of opiates in obese-diabetic ob/ob mice. Diabetologia, 30, 33–37.PubMedCrossRefGoogle Scholar
  13. Baliki, M. N., Chialvo, D. R., Geha, P. Y., Levy, R. M., Harden, R. N., et al. (2006). Chronic pain and the emotional brain: Specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain. The Journal of Neuroscience, 26, 12165–12173.PubMedCrossRefGoogle Scholar
  14. Baliki, M. N., Geha, P. Y., Apkarian, A. V., & Chialvo, D. R. (2008). Beyond feeling: Chronic pain hurts the brain, disrupting the default-mode network dynamics. The Journal of Neuroscience, 28, 1398–1403.PubMedCrossRefGoogle Scholar
  15. Ballantyne, J. C. (2007). Opioid analgesia: Perspectives on right use and utility. Pain Physician, 10, 479–491.PubMedGoogle Scholar
  16. Beaver, W. T., Wallenstein, S. L., Houde, R. W., & Rogers, A. (1967). A clinical comparison of the analgesic effects of methadone and morphine administered intramuscularly, and of orally and parenterally administered methadone. Clinical Pharmacology and Therapeutics, 8, 415–426.PubMedGoogle Scholar
  17. Bederson, J. B., Fields, H. L., & Barbaro, N. M. (1990). Hyperalgesia during naloxone-precipitated withdrawal from morphine is associated with increased on-cell activity in the rostral ventromedial medulla. Somatosensory and Motor Research, 7, 185–203.PubMedCrossRefGoogle Scholar
  18. Belgrade, M. J., Schamber, C. D., & Lindgren, B. R. (2006). The DIRE score: Predicting outcomes of opioid prescribing for chronic pain. The Journal of Pain, 7, 671–681.PubMedCrossRefGoogle Scholar
  19. Bliesener, N., Albrecht, S., Schwager, A., Weckbecker, K., Lichtermann, D., et al. (2005). Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence. The Journal of Clinical Endocrinology and Metabolism, 90, 203–206.PubMedCrossRefGoogle Scholar
  20. Bloodworth, D. (2005). Issues in opioid management. American Journal of Physical Medicine & Rehabilitation, 84, S42–S55.Google Scholar
  21. Booth, M. (1986). Opium: A history. New York, NY: St. Martin’s Press.Google Scholar
  22. Buckalew, N., Haut, M. W., Aizenstein, H., Morrow, L., Perera, S., et al. (2010). Differences in brain structure and function in older adults with self-reported disabling and nondisabling chronic low back pain. Pain Medicine, 11, 1183–1197.PubMedCrossRefGoogle Scholar
  23. Butler, S. F., Budman, S. H., Fernandez, K. C., Houle, B., Benoit, C., et al. (2007). Development and validation of the Current Opioid Misuse Measure. Pain, 130, 144–156.PubMedCrossRefGoogle Scholar
  24. Butler, S. F., Fernandez, K., Benoit, C., Budman, S. H., & Jamison, R. N. (2008). Validation of the revised Screener and Opioid Assessment for Patients with Pain (SOAPP-R). The Journal of Pain, 9, 360–372.PubMedCrossRefGoogle Scholar
  25. Caldwell, J. R., Hale, M. E., Boyd, R. E., Hague, J. M., Iwan, T., et al. (1999). Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: A double blind, randomized, multicenter, placebo controlled trial. The Journal of Rheumatology, 26, 862–869.PubMedGoogle Scholar
  26. Caldwell, J. R., Rapoport, R. J., Davis, J. C., Offenberg, H. L., Marker, H. W., et al. (2002). Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: Results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial. Journal of Pain and Symptom Management, 23, 278–291.PubMedCrossRefGoogle Scholar
  27. Caudill-Slosberg, M. A., Schwartz, L. M., & Woloshin, S. (2004). Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs. 2000. Pain, 109, 514–519.PubMedCrossRefGoogle Scholar
  28. Celerier, E., Rivat, C., Jun, Y., Laulin, J. P., Larcher, A., et al. (2000). Long-lasting hyperalgesia induced by fentanyl in rats: Preventive effect of ketamine. Anesthesiology, 92, 465–472.PubMedCrossRefGoogle Scholar
  29. Chabal, C., Erjavec, M. K., Jacobson, L., Mariano, A., & Chaney, E. (1997). Prescription opiate abuse in chronic pain patients: Clinical criteria, incidence, and predictors. The Clinical Journal of Pain, 13, 150–155.PubMedCrossRefGoogle Scholar
  30. Chang, G., Chen, L., & Mao, J. (2007). Opioid tolerance and hyperalgesia. The Medical Clinics of North America, 91, 199–211.PubMedCrossRefGoogle Scholar
  31. Chapman, C. R., Lipschitz, D. L., Angst, M. S., Chou, R., Denisco, R. C., et al. (2010). Opioid pharmacotherapy for chronic non-cancer pain in the United States: A research guideline for developing an evidence-base. The Journal of Pain, 11, 807–829.PubMedCrossRefGoogle Scholar
  32. Chiou, L. C., Liao, Y. Y., Fan, P. C., Kuo, P. H., Wang, C. H., et al. (2007). Nociceptin/orphanin FQ peptide receptors: Pharmacology and clinical implications. Current Drug Targets, 8, 117–135.PubMedCrossRefGoogle Scholar
  33. Chou, R., Fanciullo, G. J., Fine, P. G., Adler, J. A., Ballantyne, J. C., et al. (2009). Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. The Journal of Pain, 10, 113–130.PubMedCrossRefGoogle Scholar
  34. Christie, M. J. (2008). Cellular neuroadaptations to chronic opioids: Tolerance, withdrawal and addiction. British Journal of Pharmacology, 154, 384–396.PubMedCrossRefGoogle Scholar
  35. Chu, L. F., Clark, D. J., & Angst, M. S. (2006). Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: A preliminary prospective study. The Journal of Pain, 7, 43–48.PubMedCrossRefGoogle Scholar
  36. Chugh, S. S., Socoteanu, C., Reinier, K., Waltz, J., Jui, J., et al. (2008). A community-based evaluation of sudden death associated with therapeutic levels of methadone. The American Journal of Medicine, 121, 66–71.PubMedCrossRefGoogle Scholar
  37. Compton, P., Charuvastra, V. C., & Ling, W. (2001). Pain intolerance in opioid-maintained former opiate addicts: Effect of long-acting maintenance agent. Drug and Alcohol Dependence, 63, 139–146.PubMedCrossRefGoogle Scholar
  38. Compton, P., Darakjian, J., & Miotto, K. (1998). Screening for addiction in patients with chronic pain and “problematic” substance use: Evaluation of a pilot assessment tool. Journal of Pain and Symptom Management, 16, 355–363.PubMedCrossRefGoogle Scholar
  39. Cook, R. F., Bernstein, A. D., Arrington, T. L., Andrews, C. M., & Marshall, G. A. (1995). Methods for assessing drug use prevalence in the workplace: A comparison of self-report, urinalysis, and hair analysis. The International Journal of the Addictions, 30, 403–426.PubMedGoogle Scholar
  40. Cowan, D. T., Wilson-Barnett, J., Griffiths, P., Vaughan, D. J., Gondhia, A., et al. (2005). A randomized, double-blind, placebo-controlled, cross-over pilot study to assess the effects of long-term opioid drug consumption and subsequent abstinence in chronic noncancer pain patients receiving controlled-release morphine. Pain Medicine, 6, 113–121.PubMedCrossRefGoogle Scholar
  41. Cruciani, R. A., Sekine, R., Homel, P., Lussier, D., Yap, Y., et al. (2005). Measurement of QTc in patients receiving chronic methadone therapy. Journal of Pain and Symptom Management, 29, 385–391.PubMedCrossRefGoogle Scholar
  42. Daniell, H. W. (2002). Hypogonadism in men consuming sustained-action oral opioids. The Journal of Pain, 3, 377–384.PubMedCrossRefGoogle Scholar
  43. Daniell, H. W. (2008). Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain. The Journal of Pain, 9, 28–36.PubMedCrossRefGoogle Scholar
  44. Daniell, H. W., Lentz, R., & Mazer, N. A. (2006). Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency. The Journal of Pain, 7, 200–210.PubMedCrossRefGoogle Scholar
  45. Dellemijn, P. L., & Vanneste, J. A. (1997). Randomised double-blind active-placebo-controlled crossover trial of intravenous fentanyl in neuropathic pain. Lancet, 349, 753–758.PubMedCrossRefGoogle Scholar
  46. Devulder, J., Richarz, U., & Nataraja, S. H. (2005). Impact of long-term use of opioids on quality of life in patients with chronic, non-malignant pain. Current Medical Research and Opinion, 21, 1555–1568.PubMedCrossRefGoogle Scholar
  47. Dikotter, F., Laaman, L., & Xun, Z. (2004). Narcotic culture: A history of drugs in China. Chicago, IL: University of Chicago Press.Google Scholar
  48. Dogrul, A., Bilsky, E. J., Ossipov, M. H., Lai, J., & Porreca, F. (2005). Spinal L-type calcium channel blockade abolishes opioid-induced sensory hypersensitivity and antinociceptive tolerance. Anesthesia and Analgesia, 101, 1730–1735.PubMedCrossRefGoogle Scholar
  49. Dohrenwend, B. P., Raphael, K. G., Marbach, J. J., & Gallagher, R. M. (1999). Why is depression comorbid with chronic myofascial face pain? A family study test of alternative hypotheses. Pain, 83, 183–192.PubMedCrossRefGoogle Scholar
  50. Edlund, M. J., Steffick, D., Hudson, T., Harris, K. M., & Sullivan, M. (2007). Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain, 129, 355–362.PubMedCrossRefGoogle Scholar
  51. Eisendrath, S. J. (1995). Psychiatric aspects of chronic pain. Neurology, 45, S26–S34; discussion S35–S36.Google Scholar
  52. Elander, J., Lusher, J., Bevan, D., Telfer, P., & Burton, B. (2004). Understanding the causes of problematic pain management in sickle cell disease: Evidence that pseudoaddiction plays a more important role than genuine analgesic dependence. Journal of Pain and Symptom Management, 27, 156–169.PubMedCrossRefGoogle Scholar
  53. Elliott, A. M., Smith, B. H., Penny, K. I., Smith, W. C., & Chambers, W. A. (1999). The epidemiology of chronic pain in the community. Lancet, 354, 1248–1252.PubMedCrossRefGoogle Scholar
  54. Epstein, D. H., Preston, K. L., & Jasinski, D. R. (2006). Abuse liability, behavioral pharmacology, and physical-dependence potential of opioids in humans and laboratory animals: Lessons from tramadol. Biological Psychology, 73, 90–99.PubMedCrossRefGoogle Scholar
  55. Fishbain, D. A. (1999). Approaches to treatment decisions for psychiatric comorbidity in the management of the chronic pain patient. Medical Clinics of North America, 83, 737–760, vii.Google Scholar
  56. Fishbain, D. A., Cole, B., Lewis, J. E., Gao, J., & Rosomoff, R. S. (2009). Do opioids induce hyperalgesia in humans? An evidence-based structured review. Pain Medicine, 10, 829–839.PubMedCrossRefGoogle Scholar
  57. Fishbain, D. A., Cutler, R. B., Rosomoff, H. L., & Rosomoff, R. S. (1999). Validity of self-reported drug use in chronic pain patients. The Clinical Journal of Pain, 15, 184–191.PubMedCrossRefGoogle Scholar
  58. Fishbain, D. A., Rosomoff, H. L., & Rosomoff, R. S. (1992). Drug abuse, dependence, and addiction in chronic pain patients. The Clinical Journal of Pain, 8, 77–85.PubMedCrossRefGoogle Scholar
  59. Fleming, M. F., Davis, J., & Passik, S. D. (2008). Reported lifetime aberrant drug-taking behaviors are predictive of current substance use and mental health problems in primary care patients. Pain Medicine, 9, 1098–1106.PubMedCrossRefGoogle Scholar
  60. Flor, H., Fydrich, T., & Turk, D. C. (1992). Efficacy of multidisciplinary pain treatment centers: A meta-analytic review. Pain, 49, 221–230.PubMedCrossRefGoogle Scholar
  61. Foley, K. M., & Houde, R. W. (1998). Methadone in cancer pain management: Individualize dose and titrate to effect. Journal of Clinical Oncology, 16, 3213–3215.PubMedGoogle Scholar
  62. Fraser, L. A., Morrison, D., Morley-Forster, P., Paul, T. L., Tokmakejian, S., et al. (2009). Oral opioids for chronic non-cancer pain: Higher prevalence of hypogonadism in men than in women. Experimental and Clinical Endocrinology & Diabetes, 117, 38–43.CrossRefGoogle Scholar
  63. Fredheim, O. M., Borchgrevink, P. C., Hegrenaes, L., Kaasa, S., Dale, O., et al. (2006a). Opioid switching from morphine to methadone causes a minor but not clinically significant increase in QTc time: A prospective 9-month follow-up study. Journal of Pain and Symptom Management, 32, 180–185.PubMedCrossRefGoogle Scholar
  64. Fredheim, O. M., Kaasa, S., Dale, O., Klepstad, P., Landro, N. I., et al. (2006b). Opioid switching from oral slow release morphine to oral methadone may improve pain control in chronic non-malignant pain: A nine-month ­follow-up study. Palliative Medicine, 20, 35–41.PubMedCrossRefGoogle Scholar
  65. Freye, E., Anderson-Hillemacher, A., Ritzdorf, I., & Levy, J. V. (2007). Opioid rotation from high-dose morphine to transdermal buprenorphine (Transtec) in chronic pain patients. Pain Practice, 7, 123–129.PubMedCrossRefGoogle Scholar
  66. Furlan, A. D., Sandoval, J. A., Mailis-Gagnon, A., & Tunks, E. (2006). Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects. The Canadian Medical Association Journal, 174, 1589–1594.CrossRefGoogle Scholar
  67. Gagajewski, A., & Apple, F. S. (2003). Methadone-related deaths in Hennepin County, Minnesota: 1992–2002. Journal of Forensic Sciences, 48, 668–671.PubMedGoogle Scholar
  68. Galer, B. S., Coyle, N., Pasternak, G. W., & Portenoy, R. K. (1992). Individual variability in the response to different opioids: Report of five cases. Pain, 49, 87–91.PubMedCrossRefGoogle Scholar
  69. Gallagher, R. M. (2004). Biopsychosocial pain medicine and mind-brain-body science. Physical Medicine and Rehabilitation Clinics of North America, 15, 855–882, vii.Google Scholar
  70. Gallagher, R. M., Marbach, J. J., Raphael, K. G., Handte, J., & Dohrenwend, B. P. (1995). Myofascial face pain: Seasonal variability in pain intensity and demoralization. Pain, 61, 113–120.PubMedCrossRefGoogle Scholar
  71. Gallagher, R. M., & Rosenthal, L. J. (2008). Chronic pain and opiates: Balancing pain control and risks in long-term opioid treatment. Archives of Physical Medicine and Rehabilitation, 89, S77–S82.PubMedCrossRefGoogle Scholar
  72. Gallagher, R. M., & Verma, S. (1999). Managing pain and comorbid depression: A public health challenge. Seminars in Clinical Neuropsychiatry, 4, 203–220.PubMedGoogle Scholar
  73. Gallagher, R. M., Verma, S., & Mossey, J. (2000). Chronic pain. Sources of late-life pain and risk factors for disability. Geriatrics, 55, 40–44, 47.Google Scholar
  74. Gardell, L. R., Wang, R., Burgess, S. E., Ossipov, M. H., Vanderah, T. W., et al. (2002). Sustained morphine exposure induces a spinal dynorphin-dependent enhancement of excitatory transmitter release from primary afferent fibers. The Journal of Neuroscience, 22, 6747–6755.PubMedGoogle Scholar
  75. Gatti, A., Reale, C., Luzi, M., Canneti, A., Mediati, R. D., et al. (2010). Effects of opioid rotation in chronic pain patients: ORTIBARN study. Clinical Drug Investigation, 30(Suppl 2), 39–47.PubMedCrossRefGoogle Scholar
  76. Geisser, M. E., Robinson, M. E., Miller, Q. L., & Bade, S. M. (2003). Psychosocial factors and functional capacity evaluation among persons with chronic pain. Journal of Occupational Rehabilitation, 13, 259–276.PubMedCrossRefGoogle Scholar
  77. Giesecke, T., Gracely, R. H., Williams, D. A., Geisser, M. E., Petzke, F. W., et al. (2005). The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. Arthritis and Rheumatism, 52, 1577–1584.PubMedCrossRefGoogle Scholar
  78. Gillen, C., Haurand, M., Kobelt, D. J., & Wnendt, S. (2000). Affinity, potency and efficacy of tramadol and its metabolites at the cloned human mu-opioid receptor. Naunyn-Schmiedeberg’s Archives of Pharmacology, 362, 116–121.PubMedCrossRefGoogle Scholar
  79. Gimbel, J. S., Richards, P., & Portenoy, R. K. (2003). Controlled-release oxycodone for pain in diabetic neuropathy: A randomized controlled trial. Neurology, 60, 927–934.PubMedCrossRefGoogle Scholar
  80. Giugliano, D. (1984). Morphine, opioid peptides, and pancreatic islet function. Diabetes Care, 7, 92–98.PubMedCrossRefGoogle Scholar
  81. Gomez-Flores, R., & Weber, R. J. (2000). Differential effects of buprenorphine and morphine on immune and neuroendocrine functions following acute administration in the rat mesencephalon periaqueductal gray. Immunopharmacology, 48, 145–156.PubMedCrossRefGoogle Scholar
  82. Gonzalez-Barboteo, J., Porta-Sales, J., Sanchez, D., Tuca, A., & Gomez-Batiste, X. (2008). Conversion from parenteral to oral methadone. Journal of Pain & Palliative Care Pharmacotherapy, 22, 200–205.CrossRefGoogle Scholar
  83. Gordon, D. B., Dahl, J., Phillips, P., Frandsen, J., Cowley, C., et al. (2004). The use of “as-needed” range orders for opioid analgesics in the management of acute pain: A consensus statement of the American Society for Pain Management Nursing and the American Pain Society. Pain Management Nursing, 5, 53–58.PubMedCrossRefGoogle Scholar
  84. Gourlay, D. L., Heit, H. A., & Almahrezi, A. (2005). Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Medicine, 6, 107–112.PubMedCrossRefGoogle Scholar
  85. Griessinger, N., Sittl, R., & Likar, R. (2005). Transdermal buprenorphine in clinical practice – A post-marketing surveillance study in 13,179 patients. Current Medical Research and Opinion, 21, 1147–1156.PubMedCrossRefGoogle Scholar
  86. Grond, S., & Sablotzki, A. (2004). Clinical pharmacology of tramadol. Clinical Pharmacokinetics, 43, 879–923.PubMedCrossRefGoogle Scholar
  87. Guignard, B., Bossard, A. E., Coste, C., Sessler, D. I., Lebrault, C., et al. (2000). Acute opioid tolerance: Intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology, 93, 409–417.PubMedCrossRefGoogle Scholar
  88. Guststein, H. B., & Akil, H. (2006). Opioid analgesics. In L. L. Brunton, J. S. Lazo, & K. L. Parker (Eds.), Goodman and Gilman’s the pharmacological basis of therapeutics (11th ed., pp. 547–590). New York, NY: McGraw-Hill Medical.Google Scholar
  89. Guzman, J., Esmail, R., Karjalainen, K., Malmivaara, A., Irvin, E., et al. (2001). Multidisciplinary rehabilitation for chronic low back pain: Systematic review. British Medical Journal, 322, 1511–1516.PubMedCrossRefGoogle Scholar
  90. Hallinan, R., Byrne, A., Agho, K., McMahon, C., Tynan, P., et al. (2008). Erectile dysfunction in men receiving methadone and buprenorphine maintenance treatment. The Journal of Sexual Medicine, 5, 684–692.PubMedCrossRefGoogle Scholar
  91. Han, W., Ide, S., Sora, I., Yamamoto, H., & Ikeda, K. (2004). A possible genetic mechanism underlying individual and interstrain differences in opioid actions: Focus on the mu opioid receptor gene. Annals of the New York Academy of Sciences, 1025, 370–375.PubMedCrossRefGoogle Scholar
  92. Heit, H. A., & Gourlay, D. L. (2008). Buprenorphine: New tricks with an old molecule for pain management. The Clinical Journal of Pain, 24, 93–97.PubMedCrossRefGoogle Scholar
  93. Hoffman, B. M., Papas, R. K., Chatkoff, D. K., & Kerns, R. D. (2007). Meta-analysis of psychological interventions for chronic low back pain. Health Psychology, 26, 1–9.PubMedCrossRefGoogle Scholar
  94. Inturrisi, C. E. (2002). Clinical pharmacology of opioids for pain. The Clinical Journal of Pain, 18, S3–S13.PubMedCrossRefGoogle Scholar
  95. Ives, T. J., Chelminski, P. R., Hammett-Stabler, C. A., Malone, R. M., Perhac, J. S., et al. (2006). Predictors of opioid misuse in patients with chronic pain: A prospective cohort study. BMC Health Services Research, 6, 46.PubMedCrossRefGoogle Scholar
  96. Jamison, R. N., Raymond, S. A., Slawsby, E. A., Nedeljkovic, S. S., & Katz, N. P. (1998). Opioid therapy for chronic noncancer back pain. A randomized prospective study. Spine (Philadelphia, Pa 1976), 23, 2591–2600.CrossRefGoogle Scholar
  97. Jovey, R. D., Ennis, J., Gardner-Nix, J., Goldman, B., Hays, H., et al. (2003). Use of opioid analgesics for the treatment of chronic noncancer pain – A consensus statement and guidelines from the Canadian Pain Society, 2002. Pain Research & Management, 8(Suppl A), 3A–28A.Google Scholar
  98. Kalso, E., Edwards, J. E., Moore, R. A., & McQuay, H. J. (2004). Opioids in chronic non-cancer pain: Systematic review of efficacy and safety. Pain, 112, 372–380.PubMedCrossRefGoogle Scholar
  99. Kanner, R. M., & Foley, K. M. (1981). Patterns of narcotic drug use in a cancer pain clinic. Annals of the New York Academy of Sciences, 362, 161–172.PubMedCrossRefGoogle Scholar
  100. Kaplan, H., & Fields, H. L. (1991). Hyperalgesia during acute opioid abstinence: Evidence for a nociceptive facilitating function of the rostral ventromedial medulla. The Journal of Neuroscience, 11, 1433–1439.PubMedGoogle Scholar
  101. Karam, G. A., Reisi, M., Kaseb, A. A., Khaksari, M., Mohammadi, A., et al. (2004). Effects of opium addiction on some serum factors in addicts with non-insulin-dependent diabetes mellitus. Addiction Biology, 9, 53–58.PubMedCrossRefGoogle Scholar
  102. Karci, A., Tasdogen, A., Erkin, Y., Aktas, G., & Elar, Z. (2004). The analgesic effect of morphine on postoperative pain in diabetic patients. Acta Anaesthesiologica Scandinavica, 48, 619–624.PubMedCrossRefGoogle Scholar
  103. Katz, N., & Fanciullo, G. J. (2002). Role of urine toxicology testing in the management of chronic opioid therapy. The Clinical Journal of Pain, 18, S76–S82.PubMedCrossRefGoogle Scholar
  104. Katz, N. P., Sherburne, S., Beach, M., Rose, R. J., Vielguth, J., et al. (2003). Behavioral monitoring and urine toxicology testing in patients receiving long-term opioid therapy. Anesthesia and Analgesia, 97, 1097–1102, table of contents.Google Scholar
  105. King, T., Gardell, L. R., Wang, R., Vardanyan, A., Ossipov, M. H., et al. (2005). Role of NK-1 neurotransmission in opioid-induced hyperalgesia. Pain, 116, 276–288.PubMedCrossRefGoogle Scholar
  106. Kinjo, M., Setoguchi, S., Schneeweiss, S., & Solomon, D. H. (2005). Bone mineral density in subjects using central nervous system-active medications. The American Journal of Medicine, 118, 1414.PubMedCrossRefGoogle Scholar
  107. Koch, T., & Hollt, V. (2008). Role of receptor internalization in opioid tolerance and dependence. Pharmacology and Therapeutics, 117, 199–206.PubMedCrossRefGoogle Scholar
  108. Krantz, M. J., Lewkowiez, L., Hays, H., Woodroffe, M. A., Robertson, A. D., et al. (2002). Torsade de pointes associated with very-high-dose methadone. Annals of Internal Medicine, 137, 501–504.PubMedCrossRefGoogle Scholar
  109. Kreek, M. J. (2001). Drug addictions. Molecular and cellular endpoints. Annals of the New York Academy of Sciences, 937, 27–49.PubMedCrossRefGoogle Scholar
  110. Kulkarni, B., Bentley, D. E., Elliott, R., Julyan, P. J., Boger, E., et al. (2007). Arthritic pain is processed in brain areas concerned with emotions and fear. Arthritis and Rheumatism, 56, 1345–1354.PubMedCrossRefGoogle Scholar
  111. Lafisca, S., Bolelli, G., Franceschetti, F., Danieli, A., Tagliaro, F., et al. (1985). Free and bound testosterone in male heroin addicts. Archives of Toxicology Supplement, 8, 394–397.CrossRefGoogle Scholar
  112. Langleben, D. D., Ruparel, K., Elman, I., Busch-Winokur, S., Pratiwadi, R., et al. (2008). Acute effect of methadone maintenance dose on brain FMRI response to heroin-related cues. The American Journal of Psychiatry, 165, 390–394.PubMedCrossRefGoogle Scholar
  113. Laulin, J. P., Maurette, P., Corcuff, J. B., Rivat, C., Chauvin, M., et al. (2002). The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance. Anesthesia and Analgesia, 94, 1263–1269, table of contents.Google Scholar
  114. Leo, J. A., Tanga, F. Y., & Tawfik, V. L. (2004). Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia. Neuroscentist, 10, 40–52.CrossRefGoogle Scholar
  115. Levine, A. S., Morley, J. E., Gosnell, B. A., Billington, C. J., & Bartness, T. J. (1985). Opioids and consummatory behavior. Brain Research Bulletin, 14, 663–672.PubMedCrossRefGoogle Scholar
  116. Lidstone, S. C., & Stoessl, A. J. (2007). Understanding the placebo effect: Contributions from neuroimaging. Molecular Imaging and Biology, 9, 176–185.PubMedCrossRefGoogle Scholar
  117. Lusher, J., Elander, J., Bevan, D., Telfer, P., & Burton, B. (2006). Analgesic addiction and pseudoaddiction in painful chronic illness. The Clinical Journal of Pain, 22, 316–324.PubMedCrossRefGoogle Scholar
  118. Lynch, M. E. (2005). A review of the use of methadone for the treatment of chronic noncancer pain. Pain Research & Management, 10, 133–144.Google Scholar
  119. Manchikanti, L., Cash, K. A., Damron, K. S., Manchukonda, R., Pampati, V., et al. (2006). Controlled substance abuse and illicit drug use in chronic pain patients: An evaluation of multiple variables. Pain Physician, 9, 215–225.PubMedGoogle Scholar
  120. Mao, J. (2002). Opioid-induced abnormal pain sensitivity: Implications in clinical opioid therapy. Pain, 100, 213–217.PubMedCrossRefGoogle Scholar
  121. Mao, J. (2006). Opioid-induced abnormal pain sensitivity. Current Pain and Headache Reports, 10, 67–70.PubMedCrossRefGoogle Scholar
  122. Mao, J., Price, D. D., & Mayer, D. J. (1994). Thermal hyperalgesia in association with the development of morphine tolerance in rats: Roles of excitatory amino acid receptors and protein kinase C. The Journal of Neuroscience, 14, 2301–2312.PubMedGoogle Scholar
  123. Martin, B. I., Deyo, R. A., Mirza, S. K., Turner, J. A., Comstock, B. A., et al. (2008). Expenditures and health status among adults with back and neck problems. The Journal of American Medical Association, 299, 656–664.CrossRefGoogle Scholar
  124. Martucci, C., Panerai, A. E., & Sacerdote, P. (2004). Chronic fentanyl or buprenorphine infusion in the mouse: Similar analgesic profile but different effects on immune responses. Pain, 110, 385–392.PubMedCrossRefGoogle Scholar
  125. Maxwell, J. C., Pullum, T. W., & Tannert, K. (2005). Deaths of clients in methadone treatment in Texas: 1994–2002. Drug and Alcohol Dependence, 78, 73–81.PubMedCrossRefGoogle Scholar
  126. McNicol, E., Horowicz-Mehler, N., Fisk, R. A., Bennett, K., Gialeli-Goudas, M., et al. (2003). Management of opioid side effects in cancer-related and chronic noncancer pain: A systematic review. The Journal of Pain, 4, 231–256.PubMedCrossRefGoogle Scholar
  127. McQuay, H. (1999). Opioids in pain management. Lancet, 353, 2229–2232.PubMedCrossRefGoogle Scholar
  128. McWilliams, L. A., Clara, I. P., Murphy, P. D., Cox, B. J., & Sareen, J. (2008). Associations between arthritis and a broad range of psychiatric disorders: Findings from a nationally representative sample. The Journal of Pain, 9, 37–44.PubMedCrossRefGoogle Scholar
  129. Meghani, S. H., Wiedemer, N. L., Becker, W. C., Gracely, E. J., & Gallagher, R. M. (2009). Predictors of resolution of aberrant drug behavior in chronic pain patients treated in a structured opioid risk management program. Pain Medicine, 10, 858–865.PubMedCrossRefGoogle Scholar
  130. Meldrum, M. L. (2003). A capsule history of pain management. The Journal of American Medical Association, 290, 2470–2475.CrossRefGoogle Scholar
  131. Meunier, J. C., Mollereau, C., Toll, L., Suaudeau, C., Moisand, C., et al. (1995). Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature, 377, 532–535.PubMedCrossRefGoogle Scholar
  132. Michna, E., Ross, E. L., Hynes, W. L., Nedeljkovic, S. S., Soumekh, S., et al. (2004). Predicting aberrant drug behavior in patients treated for chronic pain: Importance of abuse history. Journal of Pain and Symptom Management, 28, 250–258.PubMedCrossRefGoogle Scholar
  133. Moore, R. A., & McQuay, H. J. (2005). Prevalence of opioid adverse events in chronic non-malignant pain: Systematic review of randomised trials of oral opioids. Arthritis Research & Therapy, 7, R1046–R1051.CrossRefGoogle Scholar
  134. Morley, S., Eccleston, C., & Williams, A. (1999). Systematic review and meta-analysis of randomized controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache. Pain, 80, 1–13.PubMedCrossRefGoogle Scholar
  135. Mossey, J. M., & Gallagher, R. M. (2004). The longitudinal occurrence and impact of comorbid chronic pain and chronic depression over two years in continuing care retirement community residents. Pain Medicine, 5, 335–348.PubMedCrossRefGoogle Scholar
  136. Moulin, D. E., Iezzi, A., Amireh, R., Sharpe, W. K., Boyd, D., et al. (1996). Randomised trial of oral morphine for chronic non-cancer pain. Lancet, 347, 143–147.PubMedCrossRefGoogle Scholar
  137. Nicholas, M. K., Molloy, A. R., & Brooker, C. (2006). Using opioids with persisting noncancer pain: A biopsychosocial perspective. The Clinical Journal of Pain, 22, 137–146.PubMedCrossRefGoogle Scholar
  138. Nickel, M. K., Lahmann, C., Muehlbacher, M., Nickel, C., Pedrosa Gil, F., et al. (2006). Change in instrumental activities of daily living disability in female senior patients with musculosceletal pain: A prospective, randomized, controlled trial. Archives of Gerontology and Geriatrics, 42, 247–255.PubMedCrossRefGoogle Scholar
  139. O’Brien, C. P. (Ed.). (2006). Drug addiction and drug abuse (11th ed., pp. 607–625). New York, NY: McGraw-Hill.Google Scholar
  140. Office of Applied Studies SAaMHSA. (2005). Results from the 2004 national survey on drug use and health. Rockville, MD: Department of Health and Human Services.Google Scholar
  141. Ohtani, M., Kotaki, H., Nishitateno, K., Sawada, Y., & Iga, T. (1997). Kinetics of respiratory depression in rats induced by buprenorphine and its metabolite, norbuprenorphine. The Journal of Pharmacology and Experimental Therapeutics, 281, 428–433.PubMedGoogle Scholar
  142. Ohtani, M., Kotaki, H., Sawada, Y., & Iga, T. (1995). Comparative analysis of buprenorphine- and norbuprenorphine-induced analgesic effects based on pharmacokinetic-pharmacodynamic modeling. The Journal of Pharmacology and Experimental Therapeutics, 272, 505–510.PubMedGoogle Scholar
  143. Olsen, Y., Daumit, G. L., & Ford, D. E. (2006). Opioid prescriptions by U.S. primary care physicians from 1992 to 2001. The Journal of Pain, 7, 225–235.PubMedCrossRefGoogle Scholar
  144. Olsen, G. D., Wendel, H. A., Livermore, J. D., Leger, R. M., Lynn, R. K., et al. (1977). Clinical effects and pharmacokinetics of racemic methadone and its optical isomers. Clinical Pharmacology and Therapeutics, 21, 147–157.PubMedGoogle Scholar
  145. Paice, J. A., Penn, R. D., & Ryan, W. G. (1994). Altered sexual function and decreased testosterone in patients receiving intraspinal opioids. Journal of Pain and Symptom Management, 9, 126–131.PubMedCrossRefGoogle Scholar
  146. Pain IAftSo. (1986). Classification of chronic pain: Descriptions of chronic pain syndromes and definitions of pain terms. International Association for the Study of Pain, Subcommittee on Taxonomy. Pain. Supplement, 3, S1–S226.Google Scholar
  147. Pereira, J., Lawlor, P., Vigano, A., Dorgan, M., & Bruera, E. (2001). Equianalgesic dose ratios for opioids. A critical review and proposals for long-term dosing. Journal of Pain and Symptom Management, 22, 672–687.PubMedCrossRefGoogle Scholar
  148. Piercefield, E., Archer, P., Kemp, P., & Mallonee, S. (2010). Increase in unintentional medication overdose deaths: Oklahoma, 1994–2006. American Journal of Preventive Medicine, 39, 357–363.PubMedCrossRefGoogle Scholar
  149. Pincus, T., Burton, A. K., Vogel, S., & Field, A. P. (2002). A systematic review of psychological factors as predictors of chronicity/disability in prospective cohorts of low back pain. Spine (Philadelphia, Pa 1976), 27, E109–E120.CrossRefGoogle Scholar
  150. Portenoy, R. K. (1996). Opioid therapy for chronic nonmalignant pain: A review of the critical issues. Journal of Pain and Symptom Management, 11, 203–217.PubMedCrossRefGoogle Scholar
  151. Portenoy, R. K., & Foley, K. M. (1986). Chronic use of opioid analgesics in non-malignant pain: Report of 38 cases. Pain, 25, 171–186.PubMedCrossRefGoogle Scholar
  152. Porter, J., & Jick, H. (1980). Addiction rare in patients treated with narcotics. The New England Journal of Medicine, 302, 123.PubMedGoogle Scholar
  153. Raffa, R. B., Friderichs, E., Reimann, W., Shank, R. P., Codd, E. E., et al. (1992). Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. The Journal of Pharmacology and Experimental Therapeutics, 260, 275–285.PubMedGoogle Scholar
  154. Raja, S. N., Haythornthwaite, J. A., Pappagallo, M., Clark, M. R., Travison, T. G., et al. (2002). Opioids versus antidepressants in postherpetic neuralgia: A randomized, placebo-controlled trial. Neurology, 59, 1015–1021.PubMedCrossRefGoogle Scholar
  155. Ralphs, J. A., Williams, A. C., Richardson, P. H., Pither, C. E., & Nicholas, M. K. (1994). Opiate reduction in chronic pain patients: A comparison of patient-controlled reduction and staff controlled cocktail methods. Pain, 56, 279–288.PubMedCrossRefGoogle Scholar
  156. Raphael, K. G., Janal, M. N., Nayak, S., Schwartz, J. E., & Gallagher, R. M. (2004). Familial aggregation of depression in fibromyalgia: A community-based test of alternate hypotheses. Pain, 110, 449–460.PubMedCrossRefGoogle Scholar
  157. Raphael, K. G., Natelson, B. H., Janal, M. N., & Nayak, S. (2002). A community-based survey of fibromyalgia-like pain complaints following the World Trade Center terrorist attacks. Pain, 100, 131–139.PubMedCrossRefGoogle Scholar
  158. Rasheed, A., & Tareen, I. A. (1995). Effects of heroin on thyroid function, cortisol and testosterone level in addicts. Polish Journal of Pharmacology, 47, 441–444.PubMedGoogle Scholar
  159. Rauck, R. L. (2009). What is the case for prescribing long-acting opioids over short-acting opioids for patients with chronic pain? A critical review. Pain Practice, 9, 468–479.PubMedCrossRefGoogle Scholar
  160. Reid, M. C., Engles-Horton, L. L., Weber, M. B., Kerns, R. D., Rogers, E. L., et al. (2002). Use of opioid medications for chronic noncancer pain syndromes in primary care. Journal of General Internal Medicine, 17, 173–179.PubMedCrossRefGoogle Scholar
  161. Reinscheid, R. K., Nothacker, H. P., Bourson, A., Ardati, A., Henningsen, R. A., et al. (1995). Orphanin FQ: A neuropeptide that activates an opioidlike G protein-coupled receptor. Science, 270, 792–794.PubMedCrossRefGoogle Scholar
  162. Rice, A. S., & Maton, S. (2001). Gabapentin in postherpetic neuralgia: A randomised, double blind, placebo controlled study. Pain, 94, 215–224.PubMedCrossRefGoogle Scholar
  163. Ripamonti, C., Groff, L., Brunelli, C., Polastri, D., Stavrakis, A., et al. (1998). Switching from morphine to oral methadone in treating cancer pain: What is the equianalgesic dose ratio? Journal of Clinical Oncology, 16, 3216–3221.PubMedGoogle Scholar
  164. Risdahl, J. M., Khanna, K. V., Peterson, P. K., & Molitor, T. W. (1998). Opiates and infection. Journal of Neuroimmunology, 83, 4–18.PubMedCrossRefGoogle Scholar
  165. Rohling, M. L., Binder, L. M., & Langhinrichsen-Rohling, J. (1995). Money matters: A meta-analytic review of the association between financial compensation and the experience and treatment of chronic pain. Health Psychology, 14, 537–547.PubMedCrossRefGoogle Scholar
  166. Rosenblum, A., Marsch, L. A., Joseph, H., & Portenoy, R. K. (2008). Opioids and the treatment of chronic pain: Controversies, current status, and future directions. Experimental and Clinical Psychopharmacology, 16, 405–416.PubMedCrossRefGoogle Scholar
  167. Rowbotham, M., Harden, N., Stacey, B., Bernstein, P., & Magnus-Miller, L. (1998). Gabapentin for the treatment of postherpetic neuralgia: A randomized controlled trial. The Journal of American Medical Association, 280, 1837–1842.CrossRefGoogle Scholar
  168. Russell, I. J., Kamin, M., Bennett, R. M., Schnitzer, T. J., Green, J. A., et al. (2000). Efficacy of tramadol in treatment of pain in fibromyalgia. Journal of Clinical Rheumatology, 6, 250–257.PubMedCrossRefGoogle Scholar
  169. Sacerdote, P. (2006). Opioids and the immune system. Palliative Medicine, 20(Suppl 1), s9–s15.PubMedGoogle Scholar
  170. Sacerdote, P., Manfredi, B., Mantegazza, P., & Panerai, A. E. (1997). Antinociceptive and immunosuppressive effects of opiate drugs: A structure-related activity study. British Journal of Pharmacology, 121, 834–840.PubMedCrossRefGoogle Scholar
  171. Sadava, D., Alonso, D., Hong, H., & Pettit-Barrett, D. P. (1997). Effect of methadone addiction on glucose metabolism in rats. General Pharmacology, 28, 27–29.PubMedCrossRefGoogle Scholar
  172. Schieffer, B. M., Pham, Q., Labus, J., Baria, A., Van Vort, W., et al. (2005). Pain medication beliefs and medication misuse in chronic pain. The Journal of Pain, 6, 620–629.PubMedCrossRefGoogle Scholar
  173. Schmitz, R. (1985). Friedrich Wilhelm Serturner and the discovery of morphine. Pharmacy in History, 27, 61–74.PubMedGoogle Scholar
  174. Schnitzer, T. J., Gray, W. L., Paster, R. Z., & Kamin, M. (2000). Efficacy of tramadol in treatment of chronic low back pain. The Journal of Rheumatology, 27, 772–778.PubMedGoogle Scholar
  175. Sell, L. A., Morris, J., Bearn, J., Frackowiak, R. S., Friston, K. J., et al. (1999). Activation of reward circuitry in human opiate addicts. The European Journal of Neuroscience, 11, 1042–1048.PubMedCrossRefGoogle Scholar
  176. Sindrup, S. H., & Jensen, T. S. (1999). Efficacy of pharmacological treatments of neuropathic pain: An update and effect related to mechanism of drug action. Pain, 83, 389–400.PubMedCrossRefGoogle Scholar
  177. Skurtveit, S., Furu, K., Bramness, J., Selmer, R., & Tverdal, A. (2010). Benzodiazepines predict use of opioids – A follow-up study of 17,074 men and women. Pain Medicine, 11, 805–814.PubMedCrossRefGoogle Scholar
  178. Smith, H. S. (2008). Variations in opioid responsiveness. Pain Physician, 11, 237–248.PubMedGoogle Scholar
  179. Smith, H. S., Datta, S., & Manchikanti, L. (2011). Evidence-based pharmacotherapy of chronic pain. In R. J. Moore (Ed.), Handbook of pain and palliative care. New York, NY: Springer.Google Scholar
  180. Stein, C., Reinecke, H., & Sorgatz, H. (2010). Opioid use in chronic noncancer pain: Guidelines revisited. Current Opinion in Anaesthesiology, 23, 598–601.PubMedCrossRefGoogle Scholar
  181. Stoelting, R. K. (1991). Pharmacology, physiology, & anesthetic practice. Baltimore, MD: Lippincott Williams & Wilkins.Google Scholar
  182. Tennant, F. S., Jr., Rawson, R. A., Miranda, L., & Obert, J. (1983). Outpatient treatment of prescription opioid dependence: Comparison of two methods. NIDA Research Monograph, 43, 315–321.PubMedGoogle Scholar
  183. The American Academy of Pain Medicine tAPS, American Pain Society, and the American Society of Addiction Medicine. (2001). Definitions related to the use of opioids for the treatment of pain.Google Scholar
  184. The Management of Opioid Therapy for Chronic pain Working Group. (2010). VA/DoD clinical practice guideline for management of opioid therapy for chronic pain. Washington, DC: Department of Veteran Affairs.Google Scholar
  185. Tjaderborn, M., Jonsson, A. K., Ahlner, J., & Hagg, S. (2009). Tramadol dependence: A survey of spontaneously reported cases in Sweden. Pharmacoepidemiology and Drug Safety, 18, 1192–1198.PubMedCrossRefGoogle Scholar
  186. Tracey, I., & Bushnell, M. C. (2009). How neuroimaging studies have challenged us to rethink: Is chronic pain a disease? The Journal of Pain, 10, 1113–1120.PubMedCrossRefGoogle Scholar
  187. Trescot, A. M. (2010). Review of the role of opioids in cancer pain. Journal of the National Comprehensive Cancer Network, 8, 1087–1094.PubMedGoogle Scholar
  188. Trescot, A. M., Datta, S., Lee, M., & Hansen, H. (2008). Opioid pharmacology. Pain Physician, 11, S133–S153.PubMedGoogle Scholar
  189. Turk, D. C., Swanson, K. S., & Gatchel, R. J. (2008). Predicting opioid misuse by chronic pain patients: A systematic review and literature synthesis. The Clinical Journal of Pain, 24, 497–508.PubMedCrossRefGoogle Scholar
  190. Twycross, R. G. (1977). A comparison of diamorphine with cocaine and methadone. British Journal of Clinical Pharmacology, 4, 691–693.CrossRefGoogle Scholar
  191. Vadivelu, N., & Hines, R. L. (2007). Buprenorphine: A unique opioid with broad clinical applications. Journal of Opioid Management, 3, 49–58.PubMedGoogle Scholar
  192. Vallejo, R., de Leon-Casasola, O., & Benyamin, R. (2004). Opioid therapy and immunosuppression: A review. American Journal of Therapy, 11, 354–365.CrossRefGoogle Scholar
  193. van Tulder, M. W., Ostelo, R., Vlaeyen, J. W., Linton, S. J., Morley, S. J., et al. (2000). Behavioral treatment for chronic low back pain: A systematic review within the framework of the Cochrane Back Review Group. Spine (Philadelphia, Pa 1976), 25, 2688–2699.CrossRefGoogle Scholar
  194. Vanderah, T. W., Gardell, L. R., Burgess, S. E., Ibrahim, M., Dogrul, A., et al. (2000). Dynorphin promotes abnormal pain and spinal opioid antinociceptive tolerance. The Journal of Neuroscience, 20, 7074–7079.PubMedGoogle Scholar
  195. Vestergaard, P., Rejnmark, L., & Mosekilde, L. (2006). Fracture risk associated with the use of morphine and opiates. Journal of Internal Medicine, 260, 76–87.PubMedCrossRefGoogle Scholar
  196. Vissers, K. C., Besse, K., Hans, G., Devulder, J., & Morlion, B. (2010). Opioid rotation in the management of chronic pain: Where is the evidence? Pain Practice, 10, 85–93.PubMedCrossRefGoogle Scholar
  197. Volkow, N., & Li, T. K. (2005). The neuroscience of addiction. Nature Neuroscience, 8, 1429–1430.PubMedCrossRefGoogle Scholar
  198. Vuong, C., Van Uum, S. H., O’Dell, L. E., Lutfy, K., & Friedman, T. C. (2010). The effects of opioids and opioid analogs on animal and human endocrine systems. Endocrine Reviews, 31, 98–132.PubMedCrossRefGoogle Scholar
  199. Wasan, A. D., Butler, S. F., Budman, S. H., Fernandez, K., Weiss, R. D., et al. (2009). Does report of craving opioid medication predict aberrant drug behavior among chronic pain patients? The Clinical Journal of Pain, 25, 193–198.PubMedCrossRefGoogle Scholar
  200. Wasan, A., Michna, E., Greenfield, S., & Jamison, R. (2006). Interpreting urine drug tests: Prevalence of morphine metabolites to hydromorphone in chronic pain patients treated with morphine. Regional Anesthesia and Pain Medicine, 30, A-7.Google Scholar
  201. Wasan, A. D., Wootton, J., & Jamison, R. N. (2005). Dealing with difficult patients in your pain practice. Regional Anesthesia and Pain Medicine, 30, 184–192.PubMedGoogle Scholar
  202. Watkins, L. R., & Maier, S. F. (2000). The pain of being sick: Implications of immune-to-brain communication for understanding pain. Annual Review of Psychology, 51, 29–57.PubMedCrossRefGoogle Scholar
  203. Watson, C. P., Moulin, D., Watt-Watson, J., Gordon, A., & Eisenhoffer, J. (2003). Controlled-release oxycodone relieves neuropathic pain: A randomized controlled trial in painful diabetic neuropathy. Pain, 105, 71–78.PubMedCrossRefGoogle Scholar
  204. Way, B. M., Taylor, S. E., & Eisenberger, N. I. (2009). Variation in the mu-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection. Proceedings of the National Academy of Sciences of the United States of America, 106, 15079–15084.PubMedCrossRefGoogle Scholar
  205. Webster, L. R. (2010). Considering the risks of benzodiazepines and opioids together. Pain Medicine, 11, 801–802.PubMedCrossRefGoogle Scholar
  206. Webster, L. R., Choi, Y., Desai, H., Webster, L., & Grant, B. J. (2008). Sleep-disordered breathing and chronic opioid therapy. Pain Medicine, 9, 425–432.PubMedCrossRefGoogle Scholar
  207. Webster, L. R., & Webster, R. M. (2005). Predicting aberrant behaviors in opioid-treated patients: Preliminary validation of the Opioid Risk Tool. Pain Medicine, 6, 432–442.PubMedCrossRefGoogle Scholar
  208. Weschules, D. J., & Bain, K. T. (2008). A systematic review of opioid conversion ratios used with methadone for the treatment of pain. Pain Medicine, 9, 595–612.PubMedCrossRefGoogle Scholar
  209. Wiedemer, N. L., Harden, P. S., Arndt, I. O., & Gallagher, R. M. (2007). The opioid renewal clinic: A primary care, managed approach to opioid therapy in chronic pain patients at risk for substance abuse. Pain Medicine, 8, 573–584.PubMedCrossRefGoogle Scholar
  210. Xie, J. Y., Herman, D. S., Stiller, C. O., Gardell, L. R., Ossipov, M. H., et al. (2005). Cholecystokinin in the rostral ventromedial medulla mediates opioid-induced hyperalgesia and antinociceptive tolerance. The Journal of Neuroscience, 25, 409–416.PubMedCrossRefGoogle Scholar
  211. Yilmaz, B., Konar, V., Kutlu, S., Sandal, S., Canpolat, S., et al. (1999). Influence of chronic morphine exposure on serum LH, FSH, testosterone levels, and body and testicular weights in the developing male rat. Archives of Andrology, 43, 189–196.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  1. 1.Penn Presbyterian Medical centerUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Penn Pain Medicine CenterUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations