Related Experiment Video
Updated: May 12, 2026
07:23
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Systemic synergism between codeine and morphine in three pain models in mice
Hugo F Miranda1, Viviana Noriega, Ramiro J Zepeda
1Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Medical School, University of Chile, and Cardiovascular Department, Clinical Hospital, Santiago, Chile. hmiranda@med.uchile.cl
Pharmacological Reports : PR
|April 9, 2013
Summary
Combining codeine and morphine demonstrated synergistic pain relief in mice across various pain models. This opioid combination shows potential for enhanced clinical pain management strategies.
Area of Science:
- Pharmacology
- Neuroscience
- Pain Research
Background:
- Combining analgesic agents can improve pain management.
- Codeine and morphine exert analgesic effects via opioid receptor activation.
Purpose of the Study:
- To evaluate the interaction between codeine and morphine when co-administered.
- To assess their effects in different pain models using isobolographic analysis in mice.
Main Methods:
- Isobolographic analysis was employed in mice.
- Codeine and morphine were co-administered via intraperitoneal (ip) and intrathecal (it) routes.
- Three nociceptive behavioral models were utilized: writhing test, tail flick test, and orofacial formalin test.
Main Results:
- Intrathecal administration of morphine and codeine was generally more potent than intraperitoneal administration across different tests.
- Opioid coadministration exhibited synergistic effects in acute tonic, acute phasic, and inflammatory pain models.
- Interaction indices indicated synergy, with values ranging from 0.284 to 0.440.
Conclusions:
- The observed synergy in pain relief may be linked to distinct pain transmission pathways and intracellular signaling mechanisms.
- These findings suggest potential clinical benefits of combining opioids for effective pain management.
Related Concept Videos
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...
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...
01:25Analgesia 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...
01:27Combined Effects of Drugs: Synergism
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...