Related Experiment Video
Updated: Jul 30, 2025
10:37
Development of Recombinant Proteins to Treat Chronic Pain
Published on: April 11, 2018
9.6K
TLR4 activation by lysozyme induces pain without inflammation
Saurabh Yadav1, Amrita Singh1, Ravi Kant2
1Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Frontiers in Immunology
|May 17, 2023
Summary
Lysozyme triggers pain independently of inflammation by selectively activating the TRIF pathway via TLR4. This mechanism explains chronic pain development without visible inflammation, revealing a novel pain pathway.
Area of Science:
- Immunology
- Neuroscience
- Pain Research
Background:
- Pain is often linked to inflammation, but mechanisms of inflammation-independent pain, especially chronic pain, remain unclear.
- Recent studies suggest bacterial infections can induce pain independent of inflammation, even after injury healing.
Purpose of the Study:
- To investigate the mechanism by which lysozyme induces pain without causing inflammation.
- To compare intracellular signaling pathways (MyD88 and TRIF) activated by lysozyme and LPS via TLR4.
Main Methods:
- Lysozyme was injected into mouse footpads to assess inflammation and pain.
- Intracellular signaling pathways (MyD88, TRIF) were compared upon TLR4 activation by lysozyme and LPS.
- Activation of glutamate oxaloacetate transaminase-2 (GOT2) in neurons was examined.
Main Results:
- Lysozyme injection induced pain in mice without observable inflammation.
- Lysozyme selectively activated the TRIF pathway, not the MyD88 pathway, via TLR4.
- Lysozyme activated GOT2 in neurons in a TRIF-dependent manner, enhancing glutamate response.
Conclusions:
- TLR4 activation by lysozyme can induce pain independently of significant inflammation.
- Lysozyme's selective TRIF pathway activation, unlike other TLR4 activators, leads to pain with minimal inflammation.
- This pathway may represent a novel mechanism for chronic pain development.
Keywords:
LPS -lipopolysaccharideMyD88PNS -peripheral nervous systemTLR4 – toll-like receptor 4TRIFinflammationlysozymepainMore Related Videos
09:04Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
21.0K
05:24Author Spotlight: Exploring the Initiation Mechanism of 'Three-Method and Three-Acupoint' Tuina Analgesia in Rats with Nerve Injury
Published on: January 26, 2024
569
Related Concept Videos
01:44Nociception
28.1K
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.
28.1K
01:19Formation of Lipopolysaccharides
56
Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
56
01:28Inflammatory Response
2.2K
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,...
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,...
2.2K
01:25Analgesia and Pain Management
676
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...
676
01:24Local Anesthetics: Differential Sensitivity of Nerve Fibers
882
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...
882
01:20Pain
520
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...
520