Examining biophysical and physiological factors modulating human temperature regulation

人类暴露于各种形式的热应激，例如在极端高温事件，职业任务和身体活动期间。人体体温调节系统通过启动行为反应和生理热损失机制（如出汗和血管舒张）来减轻热应激期间致命的内部温度升高。由于核心温度和/或皮肤温度的扰动都会影响出汗和皮肤血管舒张，因此对体温调节控制的普遍理解与核心温度或平均体温（核心温度和皮肤温度的复合）有关。基本假设仍然是，热损失反应的开始和幅度与核心和/或平均体温的升高成正比，任何偏差都表明体温调节功能发生了改变。然而，这种对体温调节控制的过度简化并没有考虑到核心和/或皮肤温度的变化纯粹是由于身体和周围环境之间热量传递的不平衡。最近的证据表明，出汗等体温调节反应可能不是由核心和/或皮肤温度的绝对或变化决定的，这突出了我们需要提高对人类温度调节的理解。人体的生理，以及一定程度上的行为，体温调节是一个复杂和协调的反应，包括传入热感受器、中枢整合、传出交感神经活动和终末器官功能。虽然过去几十年的研究已经评估了性别和年龄等因素如何改变终末器官的功能（如汗腺、皮肤血管），但对热感受器的整合和功能知之甚少。因此，本提案的目的是评估生理和生物物理因素如何影响温度调节控制回路的特定组成部分。随着技术的进步，创新的方案和热药理学的结合，这些研究将提供一个独特的机会来检查人类的体温调节控制回路，特别强调年龄和性别对热感统的影响。在被动和主动热应激期间结合这些方法方法将能够对人体温度调节进行全面评估。我们的目标是为人类内部和外周温度感觉的潜在机制提供新的见解，以及如何将这些传入信息整合以产生足够的热损失响应以实现热平衡。这些研究的结果将增强我们目前对热应激期间人类整个生命周期的体温调节控制的理解。

Humans are exposed to various forms of heat stress, such as during extreme heat events, occupational tasks, and physical activity. The human thermoregulatory system mitigates fatal rises in internal temperature during heat stress by initiating behavioural responses and physiological heat loss mechanisms such as sweating and vasodilation. Since perturbations in either core and/or skin temperature influence sweating and cutaneous vasodilation, the prevailing understanding of thermoregulatory control has been in relationship to core or mean body temperature (a composite of core and skin temperature). The fundamental assumption has remained that the initiation, and amplitude, of heat loss responses are proportional to elevations in core and/or mean body temperature, and any deviation is suggestive of altered thermoregulatory function. However, this oversimplification of the thermoregulatory control does not consider that changes in core and/or skin temperature are purely due to imbalances in heat transfer between the body and surrounding environment. Recent evidence has suggested that thermoregulatory responses such as sweating may not be determined by the absolute, or change, in core and/or skin temperature - highlighting the need to advance our understanding of temperature regulation in humans. Human physiological, and to an extent behavioural, thermoregulation is a complex and coordinated response including afferent thermoreceptors, central integration, efferent sympathetic activity, and end organ function. While work over the last couple decades has assessed how factors such as sex and age modify end organ function (e.g., sweat glands, cutaneous blood vessels), much less is known about thermoreceptor integration and function. Therefore, the purpose of this proposal is to evaluate how physiological and biophysical factors influence specific components of the thermoregulatory control loop. With technological advances, innovative protocols, and incorporation of thermopharmacology, these studies will provide a unique opportunity to examine the thermoregulatory control loop in humans, with particular emphasis on the impacts of age and sex on thermosensory integration. Combining these methodological approaches during passive and active heat stress will enable comprehensive evaluations of human temperature regulation. We aim to provide novel insights into the underlying mechanisms surrounding internal and peripheral temperature sensation in humans, and how this afferent information is integrated to produce a sufficient heat loss response to achieve heat balance. The results from these studies will enhance our current understanding of thermoregulatory control in humans throughout the lifespan during heat stress.