Narcotic bowel syndrome (NBS) is a subset of opioid bowel dysfunction that is characterized by chronic or frequently recurring abdominal pain that worsens with continued or escalating dosages of narcotics. This syndrome is underrecognized and may be becoming more prevalent. In the United States this may be the result of increases in using narcotics for chronic nonmalignant painful disorders, and the development of maladaptive therapeutic interactions around its use. NBS can occur in patients with no prior gastrointestinal disorder who receive high dosages of narcotics after surgery or acute painful problems, and among patients with functional gastrointestinal disorders or other chronic gastrointestinal diseases who are managed by physicians who are unaware of the hyperalgesic effects of chronic opioids. The evidence for the enhanced pain perception is based on the following: (1) activation of excitatory antianalgesic pathways within a bimodal opioid regulation system, (2) descending facilitation of pain at the rostral ventral medulla and pain facilitation via dynorphin and cholecystokinin activation, and (3) glial cell activation that produces morphine tolerance and enhances opioid-induced pain. Treatment involves early recognition of the syndrome, an effective physician–patient relationship, graded withdrawal of the narcotic according to a specified withdrawal program, and the institution of medications to reduce withdrawal effects.
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Diagnosis
The syndrome is characterized by chronic or intermittent colicky abdominal pain that worsens when the narcotic effect wears down. Although narcotics may seem helpful at first, over time the pain-free periods become shorter and tachyphylaxis occurs, leading to increasing narcotic doses. Ultimately, increasing dosages enhance the adverse effects on pain sensation and delayed motility, thereby initiating the development of NBS.
Although pain is the dominant feature, nausea, bloating, intermittent
Clinical Features
NBS remains underrecognized because of a lack of knowledge about the long-term effects of narcotics as potentiators of visceral pain and motility disturbances and difficulties in clinically distinguishing abdominal pain that results from, rather than is benefited by, narcotics. It may occur among patients with no history of GI symptoms or narcotic use who receive narcotics to treat persistent postoperative or other types of pain.
Physician–Patient Behaviors Related to Narcotics
The 5 patients presented are summarized in Table 2. Although different in their clinical presentations, they share common features relating to the physician–patient interaction that contribute to the consequence of prescribing escalating dosages of narcotics (Figure 1). Typically, a patient presents to an inpatient or outpatient service or to an emergency room with long-standing and unrelenting abdominal pain, with diagnostic evaluations showing no identifiable disorder on which to focus
Narcotic Prescribing in the Current Health Care Setting
Impressively, the United States, with 4.6% of the world’s population, uses 80% of the world’s opioids.25 Although treatments with narcotics for these and other conditions should be both controlled and limited, prescriptions actually are increasing over time, and associated with this is an accelerating incidence of narcotic abuse. From 1997 to 2002, there was greater than a 400% increase in retail sales of oxycodone and methadone.25 According to the National Institute on Drug Abuse (//www.drugabuse.gov/Infofacts/nationtreatns.html
Potential Physiologic Mechanisms for Pathologic Pain Facilitation
It is recognized that morphine and other opiates act on opioid receptors in enteric neurons with a variety of GI effects that include reduced gastrointestinal and biliary motility and secretion producing nausea, vomiting, constipation, secondary intestinal pseudo-obstruction, and gastroparesis.34 Furthermore, the cellular mechanisms for opiate tolerance (ie, reduced sensitivity to the pharmacologic actions of opiates as a result of chronic exposure) now are being uncovered.
Possibly the most
Treatment
Our treatment of NBS, as summarized in Table 3, involves a biopsychosocial approach. An effective physician–patient relationship and a consistent plan of narcotic withdrawal coupled with the initiation of effective alternative treatments to manage the pain and bowel symptoms is recommended. Treatment can be initiated when the diagnosis is made and there is reasonable evidence that no other diagnosis explains the symptoms. NBS is a positive diagnosis that occurs independent of other pathologic
Conclusions
In the United States, narcotics are now one of the most commonly prescribed medications for pain, and their use is growing. Furthermore, there has been a shift from prescribing narcotics for acute or malignant pain to chronic nonmalignant pain, including those with FGIDs, who are more vulnerable to the development of NBS. NBS occurs when patients have an increased or unresponsive pain experience along with a variety of GI motility disturbances related to the narcotics. The diagnosis is based on
Spinal cord injury (SCI) affects roughly 300,000 Americans with 17,000 new cases added annually. In addition to paralysis, 60% of people with SCI develop neurogenic bowel (NB), a syndrome characterized by slow colonic transit, constipation, and chronic abdominal pain. The knowledge gap surrounding NB mechanisms after SCI means that interventions are primarily symptom-focused and largely ineffective. The goal of the present studies was to identify mechanism(s) that initiate and maintain NB after SCI as a critical first step in the development of evidence-based, novel therapeutic treatment options.
Following spinal contusion injury at T9, we observed alterations in bowel structure and function reflecting key clinical features of NB. We then leveraged tissue-specific whole transcriptome analyses (RNAseq) and fecal 16S rRNA amplicon sequencing in combination with histological, molecular, and functional (Ca2+ imaging) approaches to identify potential mechanism(s) underlying the generation of the NB phenotype.
In agreement with prior reports focused on SCI-induced changes in the skin, we observed a rapid and persistent increase in expression of calcitonin gene-related peptide (CGRP) expression in the colon. This is suggestive of a neurogenic inflammation-like process engaged by antidromic activity of below-level primary afferents following SCI. CGRP has been shown to disrupt colon homeostasis and negatively affect peristalsis and colon function. As predicted, contusion SCI resulted in increased colonic transit time, expansion of lymphatic nodules, colonic structural and genomic damage, and disruption of the inner, sterile intestinal mucus layer corresponding to increased CGRP expression in the colon. Gut microbiome colonization significantly shifted over 28 days leading to the increase in Anaeroplasma, a pathogenic, gram-negative microbe. Moreover, colon specific vagal afferents and enteric neurons were hyperresponsive after SCI to different agonists including fecal supernatants.
Our data suggest that SCI results in overexpression of colonic CGRP which could alter colon structure and function. Neurogenic inflammatory-like processes and gut microbiome dysbiosis can also sensitize vagal afferents, providing a mechanism for visceral pain despite the loss of normal sensation post-SCI. These data may shed light on novel therapeutic interventions targeting this process to prevent NB development in patients.
2023, Handbook of Gastrointestinal Motility and Disorders of Gut-Brain Interactions, Second Edition
Abdominal pain persisting for 6 months or longer is defined as chronic abdominal pain, which can be broadly categorized into functional (e.g., irritable bowel syndrome) and structural (e.g., peptic ulcer disease, ulcerative colitis, chronic pancreatitis) gastrointestinal (GI) disorders (Grover, 20121). Rome IV has called for a change in terminology requiring that functional disorders now be called disorders of the gut-brain axis. The three most common disorders of gut-brain dysfunction associated with abdominal pain are functional dyspepsia (FD), irritable bowel syndrome (IBS), and centrally mediated abdominal pain syndrome (CAPS). CAPS is characterized by continuous or nearly continuous or frequently recurrent abdominal pain that is often severe and only rarely is related to or explained by gut function.
2023, Handbook of Gastrointestinal Motility and Disorders of Gut-Brain Interactions, Second Edition
The use of opioids has increased significantly since the 1990s, and along with it, the increase of opioid associated side effects. The two major gastrointestinal side effects of opioids use are opioid-induced bowel disorders (OIBD) and narcotic bowel syndrome (NBS). The most common OIBD is opioid-induced constipation (OIC). OIC has a negative effect on quality of life and is associated with a significant economic impact. NBS or opioid-induced hyperalgesia is characterized by the paradoxical increase in the severity of chronic abdominal pain despite the use of continuous or increasing doses of opioids prescribed for abdominal pain. These patients will have improvement of their abdominal pain when opioids are withdrawn. OIBD and NBS are under-recognized due to lack of awareness, and because these conditions may coexist with functional bowel disorders. We describe the pathophysiology and management of these disorders. Several different pharmaceutical approaches have been developed to prevent and treat OIC. Evidence-based guidelines have been developed for management of OIC.
Total pancreatectomy and islet cell autotransplantation (TPIAT) offers an effective, lasting solution for the management of chronic pancreatitis up to 5-years post-operatively. Our aim was to assess durability of TPIAT at 10-years.
Patients undergoing TPIAT for chronic pancreatitis eligible for 10-year follow-up were included. Primary outcomes, including endocrine function and narcotic requirements, were reported at 5-, 7.5-, and 10-years post-operatively.
Of the 231 patients who underwent TPIAT, 142 met inclusion criteria. All patients underwent successful TPIAT with an average of 5680.3 islet equivalents per body weight. While insulin independence tended to decrease over time (25.7% vs. 16.0% vs. 10.9%, p = 0.11) with an increase in HbA1C (7.6% vs. 8.2% vs. 8.4%, p = 0.09), partial islet function persisted (64.9% vs. 68.0% vs. 67.4%, p = 0.93). Opioid independence was achieved and remained durable in the majority (73.3% vs. 72.2% vs. 75.5%, p = 0.93). Quality of life improvements persisted, with 85% reporting improvement from baseline at 10-years. Estimated median overall survival was 202.7 months.
This study represents one of the largest series reporting on long-term outcomes after TPIAT, demonstrating excellent long-term pain control and durable improvements in quality of life. Islet cell function declines over time however stable glycemic control is maintained.
The gastrointestinal (GI) tract is composed of a series of hollow organs, subject to transient or persistent mechanical stress. Recent studies have revealed that persistent mechanical stress is present in obstructive and inflammatory conditions and alters gene transcription in the GI tract. Mechanical stress-induced gene expression (mechano-transcription) of inflammatory molecules, pain mediators, pro-fibrotic and growth factors has been shown to play a critical role in pathogenesis of motility dysfunction, visceral hypersensitivity, inflammation, and fibrosis in the gut. Specifically, mechanical stress-induced cyclo-oxygenase-2 (COX-2) and other pro-inflammatory mediators in gut smooth muscle cells account for motility dysfunction and inflammatory process. Mechano-transcription of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and other pain mediators may lead to visceral hypersensitivity. Emerging evidence suggests that mechanical stress in the gut also leads to up-regulation of certain pro-fibrotic and proliferative mediators such as connective tissue growth factor (CTGF) and osteopontin (OPN), which may contribute to fibrostenotic Crohn’s disease. In this chapter, we will discuss the pathophysiological significance of mechano-transcription of pro-inflammatory molecules, pain mediators, pro-fibrotic and growth factors in obstructive, inflammatory, and functional bowel disorders. We will also evaluate potential therapeutic targets of mechano-transcription process for the management of these disorders.
Supported by the Gastrointestinal Biopsychosocial Research Center at the University of North Carolina (National Institutes of Health grant R24 DK067674), and the University of North Carolina Center for Functional GI and Motility Disorders.
