Related Experiment Video

Updated: Aug 24, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

Morphine and endomorphin-1 differently influence pronociceptin/orphanin FQ system in neuropathic rats

Joanna Mika1, Martin K H Schäfer, Ilona Obara

  • 1Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, 35033 Marburg, Germany.

Pharmacology, Biochemistry, and Behavior
|May 26, 2004
PubMed

Insights

Morphine, but not endomorphin-1, increased pronociceptin/orphanin FQ and ORL1 receptor mRNA in rats with neuropathic pain. This suggests the nociceptin/orphanin FQ system may reduce morphine effectiveness.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Neuropathic pain is a complex condition often inadequately managed by current analgesics.
  • The pronociceptin/orphanin FQ (NOP) system and its receptor (ORL1) play a role in pain modulation.
  • Opioid receptor agonists like morphine have variable efficacy in neuropathic pain states.

Purpose of the Study:

  • To investigate the impact of intrathecal morphine and endomorphin-1 on NOP and ORL1 receptor mRNA levels in a rat neuropathic pain model.
  • To explore the interaction between micro-opioid receptor agonists and the endogenous NOP system in neuropathic pain.

Main Methods:

  • Establishment of a rat model of neuropathic pain via sciatic nerve ligation.
  • Quantification of pronociceptin/orphanin FQ and ORL1 receptor mRNA levels using in situ hybridization in specific spinal cord regions.
  • Administration of intrathecal morphine, endomorphin-1, and an ORL1 receptor antagonist (PhePsi).

Main Results:

  • Sciatic nerve ligation did not alter NOP or ORL1 mRNA in dorsal horn laminae I-VI but increased ORL1 mRNA in the ventral horn.
  • Intrathecal morphine administration increased NOP and ORL1 mRNA in dorsal horn laminae I-VI, while endomorphin-1 did not.
  • ORL1 receptor antagonist administration potentiated morphine's analgesic effect in the neuropathic pain model.

Conclusions:

  • The endogenous NOP system, known for anti-opioidergic activity, may contribute to reduced morphine responsiveness in neuropathic pain.
  • Differential effects of morphine and endomorphin-1 on the NOP system highlight distinct pathways in pain modulation.
  • Targeting the NOP system could be a strategy to enhance opioid analgesia in neuropathic pain.

More Related Videos

Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents07:05

Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents

Published on: September 10, 2018

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior12:20

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

Published on: June 10, 2013

Related Concept Videos

Opioid Receptors: Overview01:22

Opioid 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...
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid 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...
Analgesia and Pain Management01:25

Analgesia 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...
Opioid Analgesics: Morphine and Other Natural Cogeners01:20

Opioid 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...
Nociception01:44

Nociception

Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain. Thus, pain helps the...
Drug-Receptor Interaction: Agonist01:25

Drug-Receptor Interaction: Agonist

Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.