Related Experiment Video

Updated: May 19, 2026

Electrophysiological Methods to Assess Peripheral Pain Block in an Anesthetized Rat
08:05

Electrophysiological Methods to Assess Peripheral Pain Block in an Anesthetized Rat

Published on: November 21, 2025

Pain inhibition by blocking leukocytic and neuronal opioid peptidases in peripheral inflamed tissue

Anja Schreiter1, Carmen Gore, Dominika Labuz

  • 1Klinik für Anästhesiologie und operative Intensivmedizin, Freie Universität Berlin, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|August 28, 2012
PubMed

Insights

Blocking opioid degradation in injured tissues enhances natural pain relief. Inhibiting aminopeptidase N (APN) and neutral endopeptidase (NEP) boosted peripheral opioid analgesia in rats with inflammation.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Management

Background:

  • Inflammatory pain is modulated by endogenous opioid peptides.
  • Degradation of these opioids limits their therapeutic potential in peripheral tissues.

Purpose of the Study:

  • To investigate the efficacy of blocking opioid degradation in peripheral injured tissue to augment endogenous opioid analgesia.
  • To identify the sources and roles of peptidases in peripheral opioid metabolism during inflammation.

Main Methods:

  • Administration of aminopeptidase N (APN) and neutral endopeptidase (NEP) inhibitors (bestatin, thiorphan, P8B) to inflamed rat hindpaws.
  • Assessment of analgesia via mechanical nociceptive thresholds.
  • Analysis of opioid receptor involvement using antibodies and receptor antagonists.
  • Detection of APN and NEP expression and activity using flow cytometry and photospectrometry.
  • Measurement of enkephalin and dynorphin A 1-17 degradation using radioimmunoassays.

Main Results:

  • Combined APN/NEP inhibition or dual inhibitor P8B significantly elevated mechanical nociceptive thresholds.
  • Analgesia was dependent on endogenous opioids (methionine-enkephalin, leucine-enkephalin, dynorphin A 1-17) and opioid receptors (μ, δ, κ).
  • APN and NEP were expressed and metabolically active on leukocytes (macrophages, granulocytes) and sciatic nerves in inflamed tissue.
  • Inhibition of these peptidases prevented opioid degradation and enhanced peripheral opioid analgesia.

Conclusions:

  • Leukocytes and peripheral nerves are key sources of APN and NEP in inflamed tissues.
  • Blockade of these peptidases effectively promotes peripheral opioid-mediated analgesia.
  • Targeting peripheral opioid degradation represents a promising strategy for inflammatory pain management.

More Related Videos

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice07:09

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Published on: July 16, 2014

Related Concept Videos

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...
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...
Local Anesthetics: Differential Sensitivity of Nerve Fibers01:24

Local Anesthetics: Differential Sensitivity of Nerve Fibers

Local anesthetics (LAs) block the sodium channels of nerve trunks, sensory nerve endings, and neuromuscular junctions. Although LAs can block all kinds of nerves, the sensitivity of nerve fibers differs according to nerve types and structures. LAs are known to block myelinated fibers faster than unmyelinated ones. Also, they block pain or sensory neurons at low concentrations without affecting the motor neurons involved in muscle contractions. This helps relieve labor pain without affecting the...
Pain01:20

Pain

Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...
Acute Inflammation III: Local and Systemic Effects01:25

Acute Inflammation III: Local and Systemic Effects

Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...
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...