Related Experiment Video

Updated: Aug 26, 2025

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

33.5K

Opening KATP channels induces inflammatory tolerance and prevents chronic pain

Cheng Qian1, Yixin Fan2, Lijuan Zong3

  • 1Department of Pathology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China; Sir Run Run Hospital, Nanjing Medical University, Nanjing 211100, Jiangsu, China.

Brain, Behavior, and Immunity
|October 5, 2022
PubMed

Insights

Potassium channel openers (KATP) relieve chronic pain by increasing suppressor of cytokine signaling-3 (SOCS3) expression. This mechanism involves the Gas6/Axl signaling pathway in microglia, offering a new target for pain relief.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Current chronic pain treatments are inadequate, necessitating novel therapeutic strategies.
  • Previous research suggested KATP channel openers possess analgesic properties, but the mechanism remains unclear.
  • This study investigates the role of suppressor of cytokine signaling-3 (SOCS3) in KATP channel opener-mediated analgesia.

Purpose of the Study:

  • To elucidate the mechanism by which KATP channel openers attenuate chronic pain.
  • To determine if KATP channel openers upregulate SOCS3 expression and induce inflammatory tolerance.
  • To explore the involvement of the Gas6/Axl signaling pathway in this process.

Main Methods:

  • A mouse model of postoperative pain was established via plantar incision.
  • Studies utilized Growth arrest-specific 6 (Gas6)-/- and Axl-/- knockout mice.
  • In vitro experiments were conducted using the BV-2 microglia cell line.

Main Results:

  • KATP channel openers significantly reduced mechanical allodynia in the pain model.
  • Upregulated SOCS3 expression was observed in conjunction with KATP channel opener treatment.
  • Activation of the Gas6/Axl-SOCS3 signaling pathway in microglia was identified as the key mechanism.

Conclusions:

  • KATP channel opening activates the Gas6/Axl-SOCS3 pathway, inducing inflammatory tolerance.
  • This pathway effectively relieves neuroinflammation and postoperative chronic pain.
  • The findings provide a theoretical basis for using KATP channel openers as a preemptive analgesic strategy by modulating innate immunity.
Keywords:
CromakalimGas6/Axl/SOCS3 signalingInflammatory toleranceK(ATP) channelPostoperative pain

More Related Videos

Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats07:12

Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats

Published on: January 21, 2020

7.8K
Development of Recombinant Proteins to Treat Chronic Pain10:37

Development of Recombinant Proteins to Treat Chronic Pain

Published on: April 11, 2018

9.6K

Related Concept Videos

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...
763
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.
29.1K
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...
569
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.5K
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
6.6K
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
5.2K