Opioid misuse in gastroenterology and non-opioid management of abdominal pain

Abstract

Opioids were one of the earliest classes of medications used for pain across a variety of conditions, but morbidity and mortality have been increasingly associated with their chronic use. Despite these negative consequences, chronic opioid use is increasing worldwide, with the USA and Canada having the highest rates. Chronic opioid use for noncancer pain can have particularly negative effects in the gastrointestinal and central nervous systems, including opioid-induced constipation, narcotic bowel syndrome, worsening psychopathology and addiction. This Review summarizes the evidence of opioid misuse in gastroenterology, including the lack of evidence of a benefit from these drugs, as well as the risk of harm and negative consequences of opioid use relative to the brain-gut axis. Guidelines for opioid management and alternative pharmacological and nonpharmacological strategies for pain management in patients with gastrointestinal disorders are also discussed. As chronic pain is complex and involves emotional and social factors, a multimodal approach targeting both pain intensity and quality of life is best.

Figure 1. Trends in total opioid consumption by country between 1994 and 2014.

Graph indicates trends in total opioid consumption (mg per capita) per year among some of the world’s most industrialized countries. Figure adapted with permission from REF. , Pain & Policy Studies Group, University of Wisconsin–Madison.

Figure 2. Summary of opioid-induced effects within the gastrointestinal system.

Opioid-induced adverse effects in the gastrointestinal system are primarily attributed to the activation of opioid receptors (μ-type, κ-type, δ-type) within the enteric nervous system, particularly in smooth muscle cells and in the terminals of sympathetic and sensory peripheral neurons in the gastrointestinal tract. Consequences (symptoms) associated with opioid use include nausea, vomiting, constipation, abdominal distention, spasms and/or gastro-oesophageal reflux.

Figure 3. Putative mechanisms for narcotic bowel syndrome and other models of opioid-induced hyperalgesia.

The bimodal opioid receptor switches from an inhibitory to an excitatory G protein state with chronic opioid exposure (1). Activation of descending pain pathways is mediated by several mechanisms including cholecystokinin (CCK) and release of dynorphin (Dyn), activation of calcium (Ca²⁺) and potassium (K⁺) channel-mediated membrane hyperexcitability, and protein kinase C (PKC)-induced increase in presynaptic N-methyl-D-aspartate (NMDA) receptor activation. On the presynaptic side, opioids paradoxically activate ‘on cells’ projecting from the rostral ventromedial medulla leading to increased dynorphin release. Opioids also activate NMDA receptors, which in turn can cause an influx in calcium and potassium through activated channels leading to increased PKC. These mechanisms sensitize the postsynaptic neuron to pain (2). Opioids induce the immune-system-related glial cells to release pro-inflammatory cytokines into dorsal horn of the spinal cord (3). DRG, dorsal root ganglion.