Home LiteratureArticle Details
PMID: 20188495 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Opioid pharmaceuticals and addiction: the issues, and research directions seeking solutions.

Drug and alcohol dependence ·Vol. 108 ·No. 3 ·2010-05-01 ·Pages 156-65

Walwyn WM, Miotto KA, Evans CJ

Abstract

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies.

MeSH Terms
Analgesics, Opioid/chemistry,pharmacokinetics,therapeutic use Animals Behavior, Addictive/metabolism,psychology Humans Opioid-Related Disorders/metabolism,psychology Pain/drug therapy,psychology Receptors, Opioid/metabolism Receptors, Opioid, mu/metabolism Signal Transduction/drug effects,physiology
Chemicals
Analgesics, Opioid Receptors, Opioid Receptors, Opioid, mu
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Walwyn Wendy M
Shirley and Stephan Hatos Center for Neuropharmacology, Semel Institute, Los Angeles, CA 90024-1759, USA. wwalwyn@ucla.edu
Miotto Karen A
Evans Christopher J
References (88)
88 references, click to expand
  1. Chronic nonmalignant pain in primary care.
    Am Fam Physician. 2008 Nov 15;78(10):1155-62 PMID: 19035063
  2. Agonist-induced state of the delta-opioid receptor that discriminates between opioid peptides and opiate alkaloids.
    Mol Pharmacol. 1993 Jul;44(1):166-72 PMID: 8393518
  3. Chronic migraine in the population: burden, diagnosis, and satisfaction with treatment.
    Neurology. 2008 Aug 19;71(8):559-66 PMID: 18711108
  4. C-terminal splice variants of the mouse mu-opioid receptor differ in morphine-induced internalization and receptor resensitization.
    J Biol Chem. 2001 Aug 17;276(33):31408-14 PMID: 11359768
  5. Controlled-release oxycodone and pregabalin in the treatment of neuropathic pain: results of a multicenter Italian study.
    Eur Neurol. 2009;61(3):129-37 PMID: 19092248
  6. The difference between acute and chronic pain.
    Mt Sinai J Med. 1991 May;58(3):217-20 PMID: 1875958
  7. Immunosuppressive medications and hospitalization for cardiovascular events in patients with rheumatoid arthritis.
    Arthritis Rheum. 2006 Dec;54(12):3790-8 PMID: 17136752
  8. The biology of the opioid growth factor receptor (OGFr).
    Brain Res Brain Res Rev. 2002 Feb;38(3):351-76 PMID: 11890982
  9. Assessment, physiological monitoring, and consequences of inadequately treated acute pain.
    Pain Manag Nurs. 2008 Mar;9(1 Suppl):S11-21 PMID: 18294590
  10. Regulation of the postburn wound inflammatory response by gammadelta T-cells.
    Shock. 2007 Sep;28(3):278-83 PMID: 17545947
  11. Functional outcomes in patients with chronic nonmalignant pain on long-term opioid therapy.
    Pain Pract. 2008 Sep-Oct;8(5):379-84 PMID: 18844854
  12. Is paradoxical pain induced by sustained opioid exposure an underlying mechanism of opioid antinociceptive tolerance?
    Neurosignals. 2005;14(4):194-205 PMID: 16215302
  13. Pain can kill.
    Pain. 1991 Jan;44(1):3-4 PMID: 2038486
  14. Role of NK-1 neurotransmission in opioid-induced hyperalgesia.
    Pain. 2005 Aug;116(3):276-288 PMID: 15964684
  15. Management of chronic pain.
    Lancet. 1999 May 29;353(9167):1865-9 PMID: 10359427
  16. Cannabinoids against pain. Efficacy and strategies to reduce psychoactivity: a clinical perspective.
    Expert Opin Investig Drugs. 2009 Feb;18(2):125-33 PMID: 19236260
  17. Agonist-selective mechanisms of GPCR desensitization.
    Br J Pharmacol. 2008 Mar;153 Suppl 1:S379-88 PMID: 18059321
  18. A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons.
    Cell. 2001 Sep 7;106(5):619-32 PMID: 11551509
  19. Transient receptor potential channels: targeting pain at the source.
    Nat Rev Drug Discov. 2009 Jan;8(1):55-68 PMID: 19116627
  20. Are opioids associated with sleep apnea? A review of the evidence.
    Curr Pain Headache Rep. 2009 Apr;13(2):120-6 PMID: 19272277
  21. GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling.
    Trends Endocrinol Metab. 2006 May-Jun;17(4):159-65 PMID: 16595179
  22. Prolonged morphine treatment targets delta opioid receptors to neuronal plasma membranes and enhances delta-mediated antinociception.
    J Neurosci. 2001 Oct 1;21(19):7598-607 PMID: 11567050
  23. Enhanced morphine analgesia in mice lacking beta-arrestin 2.
    Science. 1999 Dec 24;286(5449):2495-8 PMID: 10617462
  24. Modulation of opioid receptor function by protein-protein interactions.
    Front Biosci (Landmark Ed). 2009 Jan 01;14:3594-607 PMID: 19273296
  25. Phosphorylation of EEA1 by p38 MAP kinase regulates mu opioid receptor endocytosis.
    EMBO J. 2005 Sep 21;24(18):3235-46 PMID: 16138080
  26. An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS(R) hydromorphone in patients with chronic cancer pain.
    BMC Palliat Care. 2009 Sep 15;8:14 PMID: 19754935
  27. Ziconotide: an update and review.
    Expert Opin Pharmacother. 2008 Jun;9(9):1575-83 PMID: 18518786
  28. Major increases in opioid analgesic abuse in the United States: concerns and strategies.
    Drug Alcohol Depend. 2006 Feb 1;81(2):103-7 PMID: 16023304
  29. Opioid switching and rotation in primary care: implementation and clinical utility.
    Curr Med Res Opin. 2009 Sep;25(9):2133-50 PMID: 19601703
  30. Dissociation of the opioid receptor mechanisms that control mechanical and heat pain.
    Cell. 2009 Jun 12;137(6):1148-59 PMID: 19524516
  31. In the arms of Morpheus the development of morphine for postoperative pain relief.
    Can J Anaesth. 2000 Apr;47(4):367-74 PMID: 10764185
  32. Opioid therapy for chronic nonmalignant pain: a review of the critical issues.
    J Pain Symptom Manage. 1996 Apr;11(4):203-17 PMID: 8869456
  33. Opiates and the development of post-injury complications: a review.
    Int J Clin Exp Med. 2008;1(1):42-9 PMID: 19079686
  34. Nociceptive and inflammatory responses induced by formalin in the orofacial region of rats: effect of anti-TNFalpha strategies.
    Int Immunopharmacol. 2009 Jan;9(1):80-5 PMID: 18957334
  35. Prescription drug abuse rises globally.
    JAMA. 2007 Mar 28;297(12):1306 PMID: 17392232
  36. Morphine acutely regulates opioid receptor trafficking selectively in dendrites of nucleus accumbens neurons.
    J Neurosci. 2003 May 15;23(10):4324-32 PMID: 12764121
  37. The impact of opioids on the endocrine system.
    Clin J Pain. 2009 Feb;25(2):170-5 PMID: 19333165
  38. Targeting nerve growth factor in pain: what is the therapeutic potential?
    BioDrugs. 2008;22(6):349-59 PMID: 18998753
  39. Diversity and complexity of the mu opioid receptor gene: alternative pre-mRNA splicing and promoters.
    DNA Cell Biol. 2005 Nov;24(11):736-50 PMID: 16274294
  40. Pharmacological aspects of successful long-term analgesia.
    Clin Rheumatol. 2006;25 Suppl 1:S9-15 PMID: 16741785
  41. Research gaps on use of opioids for chronic noncancer pain: findings from a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline.
    J Pain. 2009 Feb;10(2):147-59 PMID: 19187891
  42. Pain treatment with opioids : achieving the minimal effective and the minimal interacting dose.
    Clin Drug Investig. 2009;29 Suppl 1:3-16 PMID: 19445550
  43. Mu opioid receptor-effector coupling and trafficking in dorsal root ganglia neurons.
    Neuroscience. 2006 Oct 13;142(2):493-503 PMID: 16887280
  44. Filamin A mutant lacking actin-binding domain restores mu opioid receptor regulation in melanoma cells.
    Neurochem Res. 2008 Oct;33(10):2054-61 PMID: 18404377
  45. Procedure-Specific Pain Management: PROSPECT.
    J Perianesth Nurs. 2007 Oct;22(5):335-40 PMID: 17900505
  46. Extended-release, once-daily morphine (Avinza) for the treatment of chronic nonmalignant pain: effect on pain, depressive symptoms, and cognition.
    Pain Med. 2008 Nov;9(8):985-93 PMID: 18694449
  47. Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain.
    Pain. 2008 Jul 15;137(2):428-440 PMID: 18164818
  48. A genetic analysis of opioid-induced hyperalgesia in mice.
    Anesthesiology. 2006 May;104(5):1054-62 PMID: 16645459
  49. Substance abuse treatment need among older adults in 2020: the impact of the aging baby-boom cohort.
    Drug Alcohol Depend. 2003 Mar 1;69(2):127-35 PMID: 12609694
  50. Management of chronic nonmalignant pain: a needs assessment in an internal medicine resident continuity clinic.
    J Opioid Manag. 2008 Jul-Aug;4(4):201-11 PMID: 18837203
  51. More on current issues in pain management for the primary care practitioner. Acute pain: a multi-modal management approach.
    J Pain Palliat Care Pharmacother. 2005;19(1):69-70 PMID: 15814519
  52. Cell-type specific activation of p38 and ERK mediates calcitonin gene-related peptide involvement in tolerance to morphine-induced analgesia.
    FASEB J. 2009 Aug;23(8):2576-86 PMID: 19299480
  53. Opioid therapy for chronic pain.
    N Engl J Med. 2003 Nov 13;349(20):1943-53 PMID: 14614170
  54. Opioids for chronic noncancer pain: prediction and identification of aberrant drug-related behaviors: a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline.
    J Pain. 2009 Feb;10(2):131-46 PMID: 19187890
  55. Hyperalgesia in opioid-managed chronic pain and opioid-dependent patients.
    J Pain. 2009 Mar;10(3):316-22 PMID: 19101210
  56. 2009 Clinical Guidelines from the American Pain Society and the American Academy of Pain Medicine on the use of chronic opioid therapy in chronic noncancer pain: what are the key messages for clinical practice?
    Pol Arch Med Wewn. 2009 Jul-Aug;119(7-8):469-77 PMID: 19776687
  57. Targeting the cholinergic system as a therapeutic strategy for the treatment of pain.
    Neuropharmacology. 2007 Aug;53(2):197-206 PMID: 17543355
  58. Alternative splicing determines the post-endocytic sorting fate of G-protein-coupled receptors.
    J Biol Chem. 2008 Dec 19;283(51):35614-21 PMID: 18936093
  59. Multiple opiate receptors: déjà vu all over again.
    Neuropharmacology. 2004;47 Suppl 1:312-23 PMID: 15464147
  60. Role of rat sensory neuron-specific receptor (rSNSR1) in inflammatory pain: contribution of TRPV1 to SNSR signaling in the pain pathway.
    Pain. 2009 May;143(1-2):130-7 PMID: 19307060
  61. Probable relationship between opioid abuse and heroin use.
    Am Fam Physician. 2003 Mar 1;67(5):942, 945 PMID: 12643356
  62. A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers.
    Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):9050-5 PMID: 15932946
  63. Incentive-sensitization and addiction.
    Addiction. 2001 Jan;96(1):103-14 PMID: 11177523
  64. Association of transdermal fentanyl and oral transmucosal fentanyl citrate in the treatment of opioid naive patients with severe chronic noncancer pain.
    J Opioid Manag. 2008 Mar-Apr;4(2):111-5 PMID: 18557168
  65. Opioids for nonmalignant pain.
    Rheum Dis Clin North Am. 2008 May;34(2):387-413 PMID: 18638683
  66. Secrets of the opium poppy revealed.
    Neuropharmacology. 2004;47 Suppl 1:293-9 PMID: 15464145
  67. Opioid therapy and immunosuppression: a review.
    Am J Ther. 2004 Sep-Oct;11(5):354-65 PMID: 15356431
  68. Pain and the immune system.
    Br J Anaesth. 2008 Jul;101(1):40-4 PMID: 18397920
  69. Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction.
    Ann Intern Med. 2007 Jan 16;146(2):116-27 PMID: 17227935
  70. Beta-arrestin2 and c-Src regulate the constitutive activity and recycling of mu opioid receptors in dorsal root ganglion neurons.
    J Neurosci. 2007 May 9;27(19):5092-104 PMID: 17494695
  71. In vivo delta opioid receptor internalization controls behavioral effects of agonists.
    PLoS One. 2009;4(5):e5425 PMID: 19412545
  72. Opioids and the treatment of chronic pain: controversies, current status, and future directions.
    Exp Clin Psychopharmacol. 2008 Oct;16(5):405-16 PMID: 18837637
  73. Morphine priming in rats with chronic inflammation reveals a dichotomy between antihyperalgesic and antinociceptive properties of deltorphin.
    Neuroscience. 2007 Jan 5;144(1):263-74 PMID: 17055663
  74. Therapeutic opioids: a ten-year perspective on the complexities and complications of the escalating use, abuse, and nonmedical use of opioids.
    Pain Physician. 2008 Mar;11(2 Suppl):S63-88 PMID: 18443641
  75. p38 MAPK and beta-arrestin 2 mediate functional interactions between endogenous micro-opioid and alpha2A-adrenergic receptors in neurons.
    J Biol Chem. 2009 Mar 6;284(10):6270-81 PMID: 19126537
  76. Long-term opioid therapy: assessment of consequences and risks.
    J Pain Symptom Manage. 1996 May;11(5):274-86 PMID: 8636626
  77. Peripherally-acting opioids.
    Pain Physician. 2008 Mar;11(2 Suppl):S121-32 PMID: 18443636
  78. The current status and future perspectives of studies of cannabinoid receptor 1 antagonists as anti-obesity agents.
    Curr Top Med Chem. 2009;9(6):482-503 PMID: 19689362
  79. Analgesic effects of Sazetidine-A, a new nicotinic cholinergic drug.
    Anesthesiology. 2008 Sep;109(3):512-9 PMID: 18719450
  80. Subtypes of nonmedical prescription drug misuse.
    Drug Alcohol Depend. 2009 Jun 1;102(1-3):63-70 PMID: 19278795
  81. Regular use of prescribed opioids: association with common psychiatric disorders.
    Pain. 2005 Dec 15;119(1-3):95-103 PMID: 16298066
  82. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4).
    Eur J Neurosci. 2008 Jul;28(1):20-9 PMID: 18662331
  83. The Role of Non-opioid Analgesics for the Management of Postoperative Pain.
    Cancer Control. 1999 Mar-Apr;6(2 Suppl 1):10-13 PMID: 12118233
  84. Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function.
    Brain Behav Immun. 2008 May;22(4):606-13 PMID: 18294814
  85. JNJ-20788560 [9-(8-azabicyclo[3.2.1]oct-3-ylidene)-9H-xanthene-3-carboxylic acid diethylamide], a selective delta opioid receptor agonist, is a potent and efficacious antihyperalgesic agent that does not produce respiratory depression, pharmacologic tolerance, or physical dependence.
    J Pharmacol Exp Ther. 2009 Apr;329(1):241-51 PMID: 19151246
  86. Assessment of neuropathic pain in primary care.
    Am J Med. 2009 Oct;122(10 Suppl):S13-21 PMID: 19801048
  87. Effects of opioids on the immune system.
    Neurochem Res. 1996 Nov;21(11):1375-86 PMID: 8947928
  88. Misuse of prescription drugs could soon exceed that of illicit narcotics, UN panel warns.
    BMJ. 2007 Mar 3;334(7591):444 PMID: 17332555
Article Info
Journal
Drug and alcohol dependence
Abbr.
Drug Alcohol Depend
ISSN
1879-0046
Published
2010-05-01
Epub
2010-00-25
Pages
156-65
Language
English
Region
Ireland
NLM ID
7513587
PMCID
PMC3072810
Subset
IM
Grants
NIDA NIH HHS · P50 DA005010 · United States
NIDA NIH HHS · P50 DA005010-22 · United States
NIDA NIH HHS · DA 05010 · United States
Corrections
CommentIn
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com