American journal of gastroenterology supplements (Print)最新文献

Objectives: The paradoxical development of chronic abdominal pain is an underrecognized side effect of opioid use. Narcotic bowel syndrome (NBS), occurring in a small proportion of chronic opioid users, consists of chronic or intermittent abdominal pain, which often increases in severity despite continued or escalating dosages of opioids prescribed to relieve pain.

Methods: A PubMed search was conducted using terms such as "narcotic bowel syndrome" and "opioid hyperalgesia" through January 2014.

Results: Abdominal pain is the defining symptom of NBS and is thought to be mediated by central nervous system dysfunction; it should be distinguished from the peripheral side effects of opioids, such as nausea, bloating, intermittent vomiting, abdominal distension, and constipation. This latter cluster of symptoms is called opioid bowel dysfunction, although it may co-occur with NBS. Hypothesized mechanisms of the central effects of opioids on nociception in NBS include spinal cord inflammation and dysfunction in opioid receptor activity and related neuroanatomical substrates. With continued use, ∼6% of patients taking narcotics chronically will develop NBS, with profound consequences in terms of daily function. The primary management paradigm for NBS is a structured opioid withdrawal program accompanied by centrally acting adjunctive therapy comprising antidepressants, benzodiazepines, and clonidine to target pain, anxiety, and depression, and prevent withdrawal effects, in addition to peripherally acting agents such as laxatives (e.g., osmotic laxatives and chloride channel activators) to control transient constipation. Such structured withdrawal programs have been prospectively evaluated in small clinical trials and have met with considerable success in the short term.

Conclusions: Because rates of NBS are likely to rise, integrated intensive pharmacotherapy and psychosocial interventions are needed to help patients with NBS go off and stay off opioids. These programs will likely also reduce comorbid psychopathology and lead to adequate pain control and improved quality of life.

Opioids affect motor and sensory function throughout the gastrointestinal tract, and are frequently associated with a number of gastrointestinal symptoms including constipation, which impairs the quality of life and may limit the dose of opioid or result in discontinuation altogether. Patients with opioid-induced constipation should be assessed by careful history and physical examination, and in some cases where the diagnosis is unclear with select diagnostic tests. Few clinical studies have been conducted to assess the efficacy of various treatments. However, it is generally recommended that first-line therapy begin with opioid rotation, as well as with low-cost and low-risk approaches such as lifestyle changes, consumption of fiber-rich food, stool softeners, and laxatives.

Chronic noncancer pain is common and consequential, affecting ∼100 million people in the United States alone and costing, when direct and indirect costs are combined, in excess of $635 billion. For certain individuals, opioids may be an effective option for the management of chronic pain; however, a series of critical decisions must be made before prescribing opioids to ensure that their potential benefits and possible risks are appropriately and realistically addressed. A thorough history, physical examination, and appropriate testing, including an assessment of risk for substance abuse, misuse, or addiction, should be conducted in patients who are being considered for opioid therapy. Proactively developing a treatment plan that matches the needs and expectations of the patient, while minimizing the potential for substance abuse, is central to the success of pain management. Current standard of care suggests that for most patients, a trial of nonopioid therapies should generally be tried first. There is no single opioid of choice that universally provides the best outcomes for all patients; thus, it is critical for the health-care practitioner to become familiar with the available subclasses, formulations, and modes of administration, and base the treatment plan on clinical experience with the drug, prior patient experience, the availability of the formulation, and cost and coverage. Pain is a dynamic phenomenon in that its characteristics and response to treatment evolve over time, as does the patient's general health state. Both positive and negative changes over time may necessitate a change in medication. Opioids can be prescribed safely and effectively, and when used with appropriate attention to individual patient characteristics may have a positive impact on pain and function. When contemplating initiation of opioid analgesics, clinicians would do well to make it clear to their patient that they will be prescribed on a trial basis with a clear exit strategy for discontinuing such treatment if there is no clear benefit including lack of analgesia, insurmountable adverse effects, and/or frank misuse or abuse of the prescribed drug.

Opioid drugs have powerful antidiarrheal effects and many patients taking these drugs for chronic pain relief experience chronic constipation that can progress to opioid-induced bowel dysfunction. Three classes of opioid receptors are expressed by enteric neurons: μ-, δ-, and κ-opioid receptors (MOR, DOR, and KOR). MOR and DOR couple to inhibition of adenylate cylase and nerve terminal Ca(2+) channels and activation of K(+) channels. These effects reduce neuronal activity and neurotransmitter release. KOR couples to inhibition of Ca(2+) channels and inhibition of neurotransmitter release. In the human gastrointestinal tract, MOR, DOR, and KOR link to inhibition of acetylcholine release from enteric interneurons and purine/nitric oxide release from inhibitory motorneurons. These actions inhibit propulsive motility. MOR and DOR also link to inhibition of submucosal secretomotor neurons, reducing active Cl(-) secretion and passive water movement into the colonic lumen. These effects account for the constipation caused by opioid receptor agonists. Tolerance develops to the analgesic effects of opioid receptor agonists but not to the constipating actions. This may be due to differential β-arrestin-2-dependent opioid receptor desensitization and internalization in enteric nerves in the colon compared with the small intestine and in neuronal pain pathways. Further studies of differential opioid receptor desensitization and tolerance in subsets of enteric neurons may identify new drugs or other treatment strategies of opioid-induced bowel dysfunction.