• abdominal pain

Chronic abdominal pain may result from diverse conditions that include inflammatory diseases such as chronic pancreatitis and inflammatory bowel diseases (IBD), particularly Crohn’s disease, disorders that are associated with visceral hypersensitivity such as chronic functional abdominal pain, also referred to as centrally mediated disorders of gastrointestinal pain,1 as well as the pain component of irritable bowel syndrome which is emphasised as a significant feature of symptom-based criteria with pain at least 1 day per week.2 Treatment of chronic abdominal pain remains a challenge in clinical practice, with more and more clinicians resorting to prescribing opioid medications for pain relief. Indeed, in a systematic review and meta-analysis of patients with IBD, 21% of outpatients and 62% of hospitalised patients were opioid users.3 Among 346 patients with gastroparesis included in the National Institutes of Health Gastroparesis Consortium, upper abdominal pain was severe or very severe in 34% of patients, particularly females, with similar prevalence in idiopathic and diabetic gastroparesis and with significant association with opiate use.4

A recent review outlined novel peripheral approaches in development for visceral pain.5 Two of these approaches are worthy of additional commentary: biased µ-opioid receptor (µ-OR) ligands and targeting µ-ORs under acidic conditions.

When conventional opioids bind to µ-ORs, they induce analgesia through activation of G protein-mediated pathways. However, they also activate β-arrestin, which induces respiratory depression …