Related Experiment Video

Updated: Jun 16, 2026

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
08:35

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice

Published on: March 17, 2015

Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia

Andras Garami1, Yury P Shimansky, Eszter Pakai

  • 1Systemic Inflammation Laboratory, Trauma Research, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|January 29, 2010
PubMed

Insights

Transient receptor potential vanilloid-1 (TRPV1) antagonists can cause hyperthermia. Blocking proton activation of TRPV1 is key to preventing this side effect, not blocking heat activation.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Research

Background:

  • Transient receptor potential vanilloid-1 (TRPV1) antagonists are promising pain therapeutics.
  • A significant side effect of TRPV1 antagonists is hyperthermia.
  • TRPV1 antagonists exhibit differential blockade of heat, proton, and capsaicin activation modes.

Purpose of the Study:

  • To determine the specific modes of TRPV1 activation blockade that minimize hyperthermia.
  • To investigate the relationship between antagonist potency in different activation modes and hyperthermia.

Main Methods:

  • Studied hyperthermic responses in rats, mice, and guinea pigs using eight TRPV1 antagonists.
  • Employed mathematical modeling to quantify the contribution of each activation mode blockade to hyperthermia.

Main Results:

  • Hyperthermia is most sensitive to blockade of proton activation (0.43–0.65).
  • Sensitivity to capsaicin mode blockade is low to moderate (-0.01–0.34).
  • Heat activation blockade shows minimal to no sensitivity (0.00–0.01).

Conclusions:

  • Hyperthermia-free TRPV1 antagonists do not block proton activation, irrespective of heat activation blockade potency.
  • Reducing potency against capsaicin activation may further mitigate hyperthermia risk.

More Related Videos

Intracerebroventricular Treatment with Resiniferatoxin and Pain Tests in Mice06:04

Intracerebroventricular Treatment with Resiniferatoxin and Pain Tests in Mice

Published on: September 2, 2020

Related Concept Videos

Thermosensation01:43

Thermosensation

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...
Thermoregulation01:26

Thermoregulation

The human body has a sophisticated thermoregulation system that employs negative feedback mechanisms to maintain an optimal core temperature. When the core temperature drops, peripheral and central thermoreceptors send signals to the hypothalamus, activating the heat-promoting center. This center triggers several responses aimed at increasing the core temperature. First, vasoconstriction reduces the flow of warm blood from internal organs to the skin so that the heat is not lost from the skin,...
Increased Body Temperature01:25

Increased Body Temperature

A body temperature above  38°C  (100.4 °F) is known as fever or pyrexia, and a person with fever is termed 'febrile.' Typically, the hypothalamus, a part of the brain that acts as the body's thermostat, regulates body temperature through a thermoregulatory setpoint. It receives signals from cold and warm thermal receptors throughout the body and adjusts the body's temperature accordingly. Fever occurs when this hypothalamic setpoint is altered, usually in response to an infection or illness.
Body Temperature01:25

Body Temperature

The body's temperature, measured in degrees, is determined by the balance between heat production and dissipation to the surrounding environment. For instance, if exercising vigorously, the body will produce more heat, causing sweat and dissipating that heat. Despite extreme environmental conditions and physical exertion, the human temperature-control system maintains a constant core body temperature (the temperature of deep tissues, which are the tissues located beneath the skin and other...
Mechanism of heat transfer01:19

Mechanism of heat transfer

Understanding heat transfer mechanisms is essential for understanding how our bodies maintain balance in different environmental conditions. When the environment is thermoneutral, the body is in a state of balance, neither using nor releasing energy to maintain its core temperature. However, when the environment is not thermoneutral, the body employs four heat transfer mechanisms to maintain homeostasis: conduction, convection, evaporation, and radiation. These mechanisms facilitate heat...
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...