Related Experiment Video
Updated: May 13, 2026
06:04
Intracerebroventricular Treatment with Resiniferatoxin and Pain Tests in Mice
Published on: September 2, 2020
Targeting TRP channels for pain relief
Jill-Desiree Brederson1, Philip R Kym, Arpad Szallasi
1Neuroscience Discovery Research and Pain Discovery Research, AbbVie Inc, North Chicago, IL 60064, USA.
European Journal of Pharmacology
|March 19, 2013
Summary
Targeting temperature-sensitive Transient Receptor Potential (TRP) channels offers a promising strategy for pain management. While TRP channel antagonists show potential, challenges remain in developing safe and effective pain therapeutics.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Recent preclinical research has elucidated novel molecular mechanisms in pain generation and transduction.
- Temperature-sensitive Transient Receptor Potential (TRP) channels, or thermoTRPs, on nociceptive neurons are key targets for pain pathway intervention.
Purpose of the Study:
- To review the potential and challenges of developing TRP channel antagonists as a new class of pain therapeutics.
- To highlight the roles of specific thermoTRPs (TRPV1, TRPV3, TRPA1, TRPM8) in pain signaling and drug development.
Main Methods:
- Review of preclinical and clinical research on TRP channel modulators for pain.
- Analysis of drug development efforts focusing on TRPV1, TRPV3, TRPA1, and TRPM8 antagonists and agonists.
Main Results:
- TRPV1 desensitization via topical agonists is clinically used for chronic pain.
- TRPV1, TRPV3, and TRPA1 antagonists are in clinical trials for various pain types.
- Early TRPV1 antagonists exhibited adverse effects like hyperthermia, leading to trial withdrawals.
Conclusions:
- TRP channel antagonists represent a promising avenue for novel pain therapeutics.
- Development challenges include managing adverse effects, particularly hyperthermia associated with TRPV1 antagonists.
- Further research into second-generation TRPV1 antagonists and other TRP channel targets is ongoing.
Related Concept Videos
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...
01:43Thermosensation
Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
01:20Pain
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...
01:24Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
01:12Mechanically-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...
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...