The combination of MOR agonists with non-MOR agonists may increase the analgesic potency of MOR agonists, reduce the development of tolerance and dependence, reduce the diversion and abuse, overdose, and reduce other clinically significant side effects associated with prolonged opioid use such as constipation.
μ-Opioid receptor (MOR) agonists are analgesics used clinically for the treatment of moderate to severe pain, but their use is associated with severe adverse effects such as respiratory depression, constipation, tolerance, dependence, and rewarding effects.
While a variety of prescribed or over-the-counter (OTC) medications are available for pain management, opioid medications, especially those acting on the μ-opioid receptor (μOR) and related pathways, have proven to be the most effective, despite some serious side effects including respiration depression, pruritus, dependence, and constipation.
Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators.
Glucagon-like peptide-1 (GLP-1) is beneficial in relieving pain-related symptoms of Irritable bowel syndrome (IBS), a prevalent, multi-factorial functional bowel disorder characterized by diarrhea and/or constipation, abdominal bloating, and pain.
Relation of PON1 and CYP1A1 genetic polymorphisms to clinical findings in a cross-sectional study of a Greek rural population professionally exposed to pesticides.
Generalized linear univariate model analysis performed on the opiate-induced constipation-associated SNPs and a single CHRM3 SNP revealed an association between anticholinergic symptoms and a score of 8 SNPs (adjusted P = 0.038, permuted P = 0.002).
Reverse transcription-polymerase chain reaction and western blot experiments demonstrated that LP-YS3 upregulated c-Kit, stem cell factor, and glial cell line-derived neurotrophic factor mRNA and protein expression and downregulated transient receptor potential vanilloid 1 and nitric oxide synthase expression in small intestine tissue from constipated mice.
Excess risk of IC/PBS was observed in the first- and second-degree relatives in probands with myalgia and myositis/unspecified (fibromyalgia) and in probands with constipation.
Larger numbers of patients need to be studied to investigate whether low SP is primarily associated with the constipation or RET mutation and if it is a common feature of MEN 2B.