Related Experiment Video
Updated: Jul 3, 2026
07:23
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Morphine tolerance in the mouse ileum and colon
Gracious R Ross1, Bichoy H Gabra, William L Dewey
1Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
The Journal of Pharmacology and Experimental Therapeutics
|August 7, 2008
Summary
Constipation from morphine may occur because the colon, unlike the ileum, does not develop tolerance to the drug
Area of Science:
- Pharmacology
- Gastroenterology
- Neuroscience
Background:
- Repeated morphine administration causes tolerance to pain relief but persistent constipation.
- Opioid-induced constipation is a significant clinical challenge.
- Tolerance to opioids has been observed in the ileum but not consistently in the colon.
Purpose of the Study:
- To investigate the development of tolerance to morphine in the mouse colon.
- To determine if a lack of colonic tolerance contributes to opioid-induced constipation.
- To compare morphine tolerance in the ileum and colon.
Main Methods:
- Mice received morphine or placebo pellets for 72 hours.
- Assessed tolerance to antinociception, defecation, and intestinal/colonic transit.
- Measured contractile responses in isolated ileal and colonic muscle preparations.
Main Results:
- Morphine induced significant antinociceptive tolerance and tolerance to intestinal transit.
- Tolerance to morphine's inhibitory effects on cholinergic contractions developed in the ileum but not the colon.
- No tolerance was observed in colonic transit or defecation, despite morphine administration.
Conclusions:
- The colon's lack of tolerance to morphine's effects on muscle contractions is a key factor in opioid-induced constipation.
- This study provides evidence for the mechanism underlying opioid bowel dysfunction.
- Targeting colonic opioid receptor pathways may alleviate chronic constipation in patients using morphine.
Related Concept Videos
01:25Analgesia and Pain Management
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
01:22Opioid Receptors: Overview
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
01:17Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents
Diarrhea, a condition marked by frequent loose or watery bowel movements, can be triggered by multiple factors such as viral or bacterial infections, food intolerances, anxiety, medications, and digestive disorders. Symptoms may include abdominal pain, bloating, nausea, and cramping. Severe or prolonged diarrhea can lead to complications like electrolyte imbalances, malnutrition, and dehydration if left untreated.
Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down...
Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down...
01:20Opioid Analgesics: Morphine and Other Natural Cogeners
Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...