title: Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics.
abstract: Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward.
  
  
  CONCLUSIONS
  Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids.
authors.affiliation: Departments of Comparative Biology and Experimental Medicine and Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada, trangt@ucalgary.ca cmcahill@uci.edu.
authors.forename: Tuan
authors.initials: T
authors.lastname: Trang
authors.affiliation: Departments of Anesthesiology and Anatomy-Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Ream
authors.initials: R
authors.lastname: Al-Hasani
authors.affiliation: Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St. Louis, Missouri 63104.
authors.forename: Daniela
authors.initials: D
authors.lastname: Salvemini
authors.affiliation: Neurosciences and Mental Health Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Salter
authors.affiliation: MD Anderson Cancer Center, Houston, Texas 77030, and.
authors.forename: Howard
authors.initials: H
authors.lastname: Gutstein
authors.affiliation: Department of Anaesthesiology and Perioperative Care, University of California Irvine, Irvine, California 92697 trangt@ucalgary.ca cmcahill@uci.edu.
authors.forename: Catherine M
authors.identifier: http://orcid.org/0000-0001-7009-9083
authors.initials: CM
authors.lastname: Cahill
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D059350:Chronic Pain / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D010207:Papaver / Q000737:chemistry*
chemical_list: D000701:Analgesics, Opioid