title: Review of the effect of opioid-related side effects on the undertreatment of moderate to severe chronic non-cancer pain: tapentadol, a step toward a solution?
abstract: OBJECTIVE
  Opioids are among the most effective and potent analgesics currently available. Their utility in the management of pain associated with cancer, acute injury, or surgery is well recognized. However, extending the application of opioids to the management of chronic non-cancer pain has met with considerable resistance. This resistance is due in part to concerns related to gastrointestinal and central nervous system-related adverse events as well as issues pertaining to regulatory affairs, the development of tolerance, incorrect drug usage, and addiction. This review focuses on the incidence of opioid-related side effects and the patient and physician barriers to opioid therapy for chronic non-cancer pain. Tapentadol, a centrally acting analgesic with two mechanisms of action, micro-opioid agonism and norepinephrine reuptake inhibition, may be considered to be a partial solution to some of these issues.
  
  
  METHODS
  MEDLINE was searched for English-language articles from 1950 to February 2010 using the terms chronic non-cancer pain and opioids together and in combination with undertreatment, adherence, and compliance.
  
  
  RESULTS
  The majority of patients treated with traditional opioids experience gastrointestinal- or central nervous system-related adverse events, most commonly constipation, nausea, and somnolence. These side effects often lead to discontinuation of opioid therapy. Concerns about side effects, analgesic tolerance, dependence, and addiction limit the use of opioids for the management of chronic pain. Treatment with tapentadol appears to provide several advantages of an analgesic with a more favorable side-effect profile than the classic micro-opioid receptor agonist oxycodone (especially related to gastrointestinal tolerability).
  
  
  CONCLUSIONS
  The pervasiveness of opioid-associated side effects and concerns related to tolerance, dependence, and addiction present potential barriers to the approval and use of opioids for the management of chronic non-cancer pain. The lower incidence of opioid-associated adverse events and possibly fewer withdrawal symptoms, combined with a satisfactory analgesic profile associated with tapentadol, suggest its potential utility for the management of chronic non-cancer pain. This review will focus on the incidence of opioid-related side effects and barriers to opioid therapy that are available as English-language articles in the MEDLINE index, and as such, it is a representative but not an exhaustive review of the current literature.
authors.affiliation: Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, FL 33101-6370, USA. kcandiotti@miami.edu
authors.forename: Keith A
authors.initials: KA
authors.lastname: Candiotti
authors.forename: Melvin C
authors.initials: MC
authors.lastname: Gitlin
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D004361:Drug Tolerance; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D009369:Neoplasms / Q000150:complications; D009293:Opioid-Related Disorders / Q000209:etiology / Q000517:prevention & control; D010146:Pain / Q000188:drug therapy* / Q000473:pathology; D010636:Phenols / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000077432:Tapentadol
chemical_list: D000701:Analgesics, Opioid; D010636:Phenols; D000077432:Tapentadol