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Introduction
Fever is a reaction of the body to infection or inflammation (1). On the one hand, it is beneficial to the body, because it activates the immune system and accelerates the anabolism, which is conducive to killing bacteria and viruses (1–3). On the other hand, it is harmful to the body, because it causes the heart to beat faster-10 pulses/min more with every increase of 1°C, resulting in an additional burden on the heart. High fever also causes cell degeneration, resulting in multi-organ dysfunction. Paracetamol (4,5), a common febrifuge at present, is the first synthetic febrifuge with preferred effects on lowering the temperature (6). But for patients with long-term fever (2 weeks or more), there is a lack of evidence for safety with long-term use of paracetamol (7–9). In addition, long-term fever is difficult for the human body to tolerate and causes great discomfort to the patient. At present in clinical applications, certain febrifuges work slowly with a short action time, resulting in recurring conditions; and some febrifuge treatments work fast, but with many side-effects (9). Studies on antipyretic mechanisms are beneficial for the development of new febrifuges to provide clinical fever patients with more effective treatments.
In 1949, Dubois (10) posed the question ‘Why are fever temperatures over 41°C rare?’ It is indicated that the body also starts a mechanism to limit the fever range during a rising temperature in order to prevent irreversible damage. Endogenous temperature negative regulators already discovered include lipoprotein 1 (11), arginine vasopressin (AVP) (11) and the melanocyte-stimulating hormone (MSH) (11). They gradually increase during a rising temperature and play a role in the control of the temperature.
In 1997, Caterina et al (12) successfully cloned a receptor that can be activated by capsaicin (a derivative of vanilloids). Therefore, transient receptor potential vanilloid (TRPV1) was also called a capsaicin receptor or vanillic acid receptor. It is a non-selective cation channel that mainly results in the flow of Ca2+. Under in vitro experimental conditions, it can be activated by a variety of physical and chemical factors, which mainly include capsaicin, heat greater than 43°C and protons [e.g., acid (pH <5.3)] (12,13). TRPV1 is associated with various sensory functions and its temperature-sensitive property has attracted increasing attention (14–18).
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