Turning down the body heat: A novel mechanism for TRPV1 antagonist-induced hyperthermia

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...

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,...

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...

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...

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 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...