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Recent advances in thermoregulation

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Thermoregulation is the maintenance of a relatively constant core body temperature. Humans normally maintain a body temperature at 37°C, and maintenance of this relatively high temperature is critical to human survival. This concept is so important that control of thermoregulation is often the principal example cited when teaching physiological homeostasis. A basic understanding of the processes underpinning temperature regulation is necessary for all undergraduate students studying biology and biology-related disciplines, and a thorough understanding is necessary for those students in clinical training. Our aim in this review is to broadly present the thermoregulatory process taking into account current advances in this area. First, we summarize the basic concepts of thermoregulation and subsequently assess the physiological responses to heat and cold stress, including vasodilation and vasoconstriction, sweating, nonshivering thermogenesis, piloerection, shivering, and altered behavior. Current research is presented concerning the body's detection of thermal challenge, peripheral and central thermoregulatory control mechanisms, including brown adipose tissue in adult humans and temperature transduction by the relatively recently discovered transient receptor potential channels. Finally, we present an updated understanding of the neuroanatomic circuitry supporting thermoregulation. Copyright © 2015 The American Physiological Society.
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Staying Current
Recent advances in thermoregulation
Etain A. Tansey and Christopher D. Johnson
Centre for Biomedical Sciences Education, Queen’s University, Belfast, Northern Ireland
Submitted 19 September 2014; accepted in final form 17 June 2015
Tansey EA, Johnson CD. Recent advances in thermoregulation. Adv
Physiol Educ 39: 139 –148, 2015; doi:10.1152/advan.00126.2014.—Ther-
moregulation is the maintenance of a relatively constant core body
temperature. Humans normally maintain a body temperature at 37°C,
and maintenance of this relatively high temperature is critical to
human survival. This concept is so important that control of thermo-
regulation is often the principal example cited when teaching physi-
ological homeostasis. A basic understanding of the processes under-
pinning temperature regulation is necessary for all undergraduate
students studying biology and biology-related disciplines, and a thor-
ough understanding is necessary for those students in clinical training.
Our aim in this review is to broadly present the thermoregulatory
process taking into account current advances in this area. First, we
summarize the basic concepts of thermoregulation and subsequently
assess the physiological responses to heat and cold stress, including
vasodilation and vasoconstriction, sweating, nonshivering thermogen-
esis, piloerection, shivering, and altered behavior. Current research is
presented concerning the body’s detection of thermal challenge,
peripheral and central thermoregulatory control mechanisms, includ-
ing brown adipose tissue in adult humans and temperature transduc-
tion by the relatively recently discovered transient receptor potential
channels. Finally, we present an updated understanding of the neuro-
anatomic circuitry supporting thermoregulation.
transient receptor potential channel; preoptic area of the hypothala-
mus; set point; brown adipose tissue; thermoregulation; heat; cold
AN UNDERSTANDING of body temperature regulation is necessary
to learn the basic concept of homeostasis and for a wide variety
of physiological and clinical applications. It is covered in most
elementary physiology courses, but often with a degree of
superficiality and dogma, due to time and content constraints.
As research in this area has progressed over the last few
decades, major advances in our understanding have been made,
particularly in the central circuitry involved in thermoregula-
tory control and in the peripheral sensory mechanisms of
temperature transduction. These advances have not necessarily
filtered through to general textbooks that form the cornerstone
of many medical-related and basic science courses (see Ref.
26). In the present article, we describe the processes of ther-
moregulation, taking these recent advances into account so that
those involved in teaching thermoregulation provide a more
up-to-date representation.
Normal core body temperature is around 37°C and con-
trolled within a narrow range (33.2–38.2°C) and narrowing
further when disregarding oral measurements in favor of rectal,
tympanic, or axillary measurements (68). There are normal
fluctuations that occur throughout the day (circadian rhythm),
throughout a month (menstrual cycle), and throughout a life-
time (aging). Abnormal core temperature deviations of even a
couple of degrees will challenge the body’s thermoregulatory
mechanisms, and swings in temperature outside the normal
range can prove fatal. For example, beyond a body temperature
of 42°C, cytotoxicity occurs with protein denaturation and
impaired DNA synthesis (38), resulting in end-organ failure
and neuronal impairment. If body temperature drops below
27°C (severe hypothermia), the associated neuromuscular, car-
diovascular, hematological, and respiratory changes can
equally prove fatal (40). Despite the need for tight regulation of
core temperature, humans can survive in the most inhospitable
of places and can challenge their thermoregulatory capacity in
the most extreme ways. Humans participate in the Marathon
Des Sables (a 251-km endurance running challenge in the
Sahara desert, a place where day time temperatures can reach
50°C) and ice diving, where water temperatures may only be a
few degrees above freezing. How is it possible that they can do
this and survive?
To ensure optimal physiological function and survival, hu-
mans must be able to preserve core body temperature (within
the head, thorax, and abdomen) in the face of environmental
temperature challenges. Thus, heat gain to the body must equal
heat loss.
As humans are endothermic homeotherms, we produce our
own body heat and can regulate our body temperature. Our
high core temperature is achieved principally through heat
production as a result of metabolism. Heat transfer always
occurs down a thermal gradient (from hot to cold) through the
processes of radiation, conduction, and/or convection. As hu-
mans are often the hottest objects in a given environment, the
normal direction of heat transfer is from the body to the
surroundings. However, as core temperature rises, heat loss
through evaporation becomes the primary mechanism of heat
dissipation.
The following heat balance equation addresses the internal
and external factors that contribute to thermal balance and,
therefore, the maintenance of core temperature:
Heat storage metabolism work evaporation
radiation conduction convection
where
Metabolism refers to the chemical reactions occurring within
the body that produce heat. During exercise, the working
muscle liberates large amounts of heat.
Work is the external work done.
Evaporation is the heat loss to environment as water vapor-
ized from the respiratory passages and skin surface. Total
sweat vaporized from skin depends on the following three
factors:
1. The surface area exposed to the environment
2. The temperature and relative humidity of ambient air
3. Convective air currents around the body
Address for reprint requests and other correspondence: C. D. Johnson,
Centre for Biomedical Sciences Education School of Medicine, Dentistry and
Biomedical Science Queen’s Univ., Whitla Medical Bldg., 97 Lisburn Road,
Belfast BT9 7AE, Northern Ireland (e-mail: c.johnson@qub.ac.uk).
Adv Physiol Educ 39: 139–148, 2015;
doi:10.1152/advan.00126.2014.
1391043-4046/15 Copyright © 2015 The American Physiological Society
Radiation is the electromagnetic radiation (heat) transferred
to bodies not in contact, including the ultraviolet light
radiation from the sun, which penetrates through to the
surface of the earth, and the infrared radiation from the body.
Conduction is the movement of heat to/from the body
directly to objects in contact with the body. Usually the
amount of heat exchanged in this way is minimal.
Convection is the transfer of heat to a moving gas or liquid.
When a body is warm, the air molecules that make contact
with the body will be warmed, reducing their density, which
causes the molecules to rise and be replaced with cooler air.
Convective heat exchange is increased by movement of the
body in air or water or movement of air or water across the
skin.
When the heat storage is zero, the body is thermally balanced.
In humans, normal thermoregulation involves a dynamic bal-
ance between heat production/gain and heat loss, thereby
minimalizing any heat exchange with the environment. Thus, a
constant core temperature is maintained.
Temperature Regulation
When discussing body temperature, we usually refer to the
central core and peripheral shell temperatures. The core tem-
perature reflects the temperature within the “deep” body tis-
sues, organs that have a high level of basal metabolism (such
as the brain, heart, and liver). The shell temperature is influ-
enced by blood flow to the skin, which is raised with a high
core temperature, and environmental temperature. It is usually
measured at the skin of hands and feet. The surface area-to-
mass ratio of these sites is high (for example, the surface
area-to-mass ratio of each hand is four to five times greater
than that of the body) (72), and it is known that the surface-
area-to-mass ratio is important to the transfer of thermal
energy. With a high surface-area-to-mass ratio, the hand will
chill faster than the torso, which has a lower surface area-to-
mass ratio. Notwithstanding this, the shell temperature is an
important indicator of the heat exchange requirements of the
body. Shell temperature is usually around 4°C lower than core
temperature. In a warm environment, the difference in temper-
ature between the core and shell decreases as skin blood flow
is increased and skin temperature approaches ambient temper-
ature (see Skin blood vessels below). As humans, we are
generally warmer than the ambient temperature, and so the
general flow of heat is from the shell to the environment.
During cold stress, skin blood flow is reduced, leading to a
decrease in shell temperature and conservation of heat to the
core. Temperature gradients between the core and skin can be
a useful nonspecific monitor of thermal status. For example,
there is an increased gradient between core and peripheral
temperature in shock states, and the gradient is useful in
distinguishing between cardiovascular or respiratory causes of
dyspnea (16).
The hypothalamus is the coordinating or central integration
center for thermoregulation. Evidence suggests that it is the
preoptic anterior hypothamalus that is the most important
region for autonomic temperature control (57). The input to the
hypothalamus comes from peripheral as well as central ther-
moreceptors. Recent experimental work from a number of
laboratories has provided neural substrates for thermoregula-
tory control and is discussed in more detail below. Both
peripheral and central thermoreceptors have two subtypes:
those responding to cold and those responding to warmth.
Peripheral thermoreceptors are located in the skin, where cold
receptors are more abundant than warm receptors. Warm
central thermoreceptors, located in the hypothalamus, spinal
cord, viscera, and great veins, are more numerous than cold
thermoreceptors. The impact of central thermoreceptor activa-
tion is most significant in terms of core temperature, and it
seems that the activation of warm thermoreceptors causes
inhibition of cold receptors (28). Table 1 shows physiological
and behavioral responses to the activation of these thermal
receptors.
Effector Organ Responses to an Increase in Body
Temperature
Skin blood vessels. The skin plays a substantive role in the
thermoregulatory process. In response to increased or de-
creased ambient or internal temperatures, skin blood flow is
modified accordingly through sympathetic vasodilation and
vasoconstriction mechanisms, respectively. Heat is dissipated
from the body when blood is brought in close proximity to the
skin’s surface. This is achieved through vasodilation of skin
blood vessels.
Table 1. Physiological and behavioral responses to the activation of thermoreceptors
Body Temperature
Stimulus Sensors Control Center Effectors Responses
Increase Peripheral and central
thermoreceptors
Hypothalamus 1. Skin blood vessels 1. Arteriolar and arteriovenous anastomosis vasodilation
2. Sweat glands 2. Sweating
3. Endocrine tissue 3. Decreased metabolic rate (adrenal and thyroid
glands)
4. Behavior 4. Reduced activity, stretched body position, and loss of
appetite
Decrease Peripheral and central
thermoreceptors
Hypothalamus 1. Skin blood vessels 1. Arteriolar and arteriovenous anastomosis
vasoconstriction
2. Arrector pili muscles 2. Piloerection and air trapping
3. Skeletal muscles 3. Shivering thermogenesis
4. Endocrine tissue 4. Increased metabolic rate (adrenal and thyroid glands
and brown adipose tissue)
5. Behavior 5. Increased activity, huddled body position, and
increased appetite
6. Brown adipose tissue 6. Nonshivering thermogenesis
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The mechanisms of thermal control for the cutaneous circu-
lation have been thoroughly reviewed recently (29 –31). The
autonomic nervous system plays a major role in the control of
blood flow to the skin (15). Hair-bearing skin (nonglabrous
skin) is innervated by both noradrenergic vasoconstrictor and
cholinergic vasodilator nerves, whereas nonhair-bearing skin
(glaborous skin), present on the palms, soles, and lips, is
innervated solely by vasoconstrictor nerve fibers.
In normothermia, there is a baseline level of vasoconstrictive
tone. In glaborous skin, the principal response to heat is to
increase cutaneous blood flow through passive vasodilation of
blood vessels through sympathetic nervous activity withdrawal
(25, 32). The presence of numerous arteriovenous anastomoses
in glaborous skin can lead to large changes in blood flow to
these regions, for example, in heat, arteriovenous anastomoses
open and blood flows directly from artery to vein, bypassing
high-resistance arterioles and capillary loops (Fig. 1).
In nonglarborous skin, if the convective heat loss resulting
from relaxation of vasoconstrictor tone is insufficient to cool
the core, then a further increase in skin blood flow can occur by
active vasodilatation (31), thus increasing convective heat loss
further. This active vasodilation is, at least in part, in response
to the release of acetylcholine and other cotransmitters from
sympathetic cholinergic nerves and can increase cutaneous
blood flow from 300 ml/min up to or exceeding 8 l/min (31).
Various hypotheses that have been proposed with regard to the
mechanisms involved in cutaneous active vasodilation. Very
little is known for certain about the control processes; however,
the following have been proposed (31):
1. Acetylcholine is the most important chemical for initial-
ising active vasodilator responses to body heating, but cotrans-
mitter(s) appear to be principally responsible for the overall
response. Candidates include vasoactive intestinal peptide,
substance P, histamine, prostaglandins, and transient receptor
potential (TRP)V1 receptor activation.
2. The cholinergic nerves that govern sweating may be the
same as those that control active vasodilation. This hypothesis
originates from the fact that active vasodilation and sweating
seem to occur concurrently.
3. There seems to be a role for nitric oxide in active
vasodilation as the response is attenuated by nitric oxide
synthase inhibition.
Sweat glands. Sweat production and the subsequent evapo-
ration are the principal modes of heat loss in humans when
ambient temperature rises as well as during exercise. In fact,
evaporative cooling is the only mechanism of heat loss once
ambient temperature exceeds body temperature. Exposure to a
hot environment, or exercise, elevates core and skin tempera-
tures, both of which contribute to the increased sweat rate. The
threshold for sweating normally exceeds the threshold for
vasoconstriction by 0.2°C. However, it is known that sweat-
ing begins within seconds of the onset of exercise (74), before
any measureable changes in internal temperature. This is
thought to be mediated by a combination of inputs from central
command and the exercise pressor reflex (61).
Sweat is released by eccrine glands, which are distributed in
large numbers (1.6 4 million) over the entire surface of the
body, with regional distributions in density. Sweating is me-
diated by the activation of sympathetic cholinergic fibers (62).
Evaporation of sweat allows heat to be transferred to the
environment as water vapor from respiratory passages and the
skin surface. The major limiting factor in a human’s ability to
maintain body temperature in the face of a thermal challenge is
the availability of water for sweat production. High volumes of
sweat can be produced if a person becomes heat acclimatized,
2–3 l/h (2), compared with 1 l/h in nonacclimatized individuals
(3). Heat acclimatization enhances the sweating mechanism
and has previously been associated with a redistribution of
sweat secretion toward the limbs (28). This could potentially
be desirable as limbs have a relatively large surface area-to-
mass ratio. An elevation in sweating and evaporation at these
sites could therefore enhance thermal homeostasis. However,
more recent evidence suggests that a redistribution of sweating
from the trunk to the limbs does not occur (55, 71).
With heat acclimatization, there is a lower body temperature
threshold for sweating, and sweat gland sensitivity and capac-
ity improves, so for a given core temperature, the sweat rate
increases (8, 17, 37, 56, 58). An increased sweat rate alters the
composition of sweat and is particularly associated with de-
pletion of plasma Na
and Cl
concentrations. However,
acclimatization has been shown to attenuate this reduction.
This is likely to be related to the increased renin and aldoste-
rone levels that have been found in acclimatized individuals
producing a lower sweat Na
concentration (49).
Behavioral adaptations. Physiological thermoregulatory
mechanisms have a finite capacity. Behavioral thermoregula-
tion does not; therefore, changes in human behavior can be
extremely effective in response to a change in body tempera-
ture. Behavioral thermoregulation means that we can con-
sciously and intentionally alter the heat exchange that takes
place with our environments. For example, we can seek shelter
from extreme heat by turning on the heating, grabbing a
sweater, staying in the shade, consume ice-cold drinks, etc. (for
a review, see Ref. 22).
Exercise in heat. Humans usually encounter thermal stress
through adverse weather conditions, but thermal stress can
result from the body’s overproduction of heat (e.g., during
exercise or fever). Exercise of itself will increase body tem-
Epidermis
Dermis
Capillary loop
Venous plexus
Vein
Arteriole Arteriovenous
anastomosis
Postganglionic sympathetic neuron
Oxygenated blood
Deoxygenated blood
Sympathetic varicosities
Precapillary sphincter
Fig. 1. Control of peripheral blood flow to glaborous skin. With permission
from (69). Note the presence of arteriovenous anastomoses, which have a rich
supply of sympathetic vasoconstrictive fibers. The arteriovenous anastomoses
connect arterioles directly to the venous plexus. Increased sympathetic tone in
response to a decrease in core temperature constricts arterioles and reduces
blood flow through arteriovenous anastomoses to almost nothing, thereby
reducing heat loss from the surface of the skin. In response to an increase in
body temperature, the withdrawal of sympathetic tone leads to passive dilation
of arterioles and arteriovenous anastomoses and enables heat loss by increasing
blood flow to the venous plexus. Precapillary sphincters are only sparsely
innervated by sympathetic nerves. At rest, there is a high degree of sympathetic
tone to the skin.
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perature. This may be, in part, due to an initial cutaneous
vasoconstriction, along with vasoconstriction in other nonac-
tive muscle vascular beds (splanchnic, renal, etc.), that results
in more of the cardiac output being available to active skeletal
muscle (6, 33). Thus, exercising in the heat represents a
particular challenge as heat loss is more difficult to maintain. It
is associated with early fatigue and decrements in exercise
capacity (23) and performance (70). If accompanied by a high
relative humidity, the situation is exacerbated. This is princi-
pally due to the fact that less sweat can be evaporated from the
skin’s surface in humid environments (the sweating response to
heat acclimatization is described above).
The development of fatigue during exercise in the heat is not
associated with a single factor but rather involves the interac-
tion of many physiologic processes (52). At high exercise
intensities or during prolonged exercise in the heat, heart rate
increases and stroke volume reduces in parallel with a rise in
core temperature. In addition, cutaneous blood flow plateaus at
a core temperature of 38°C (24). Therefore, beyond this core
temperature, the ability of the athlete to dissipate heat is
reduced. A circulatory conflict is observed between the skin
and skeletal muscle, which contributes to fatigue. This situa-
tion is made all the worse if accompanied by substantial sweat
loss and dehydration.
Training or repeated bouts of exercise have been shown to
improve exercise performance (39) through various physiolog-
ical adaptations; the most important of these are changes that
facilitate increased peripheral blood flow while maintaining
arterial blood pressure. Endurance training and heat acclima-
tization have been shown to improve vasodilatory ability (5, 7).
There are alterations in energy metabolism when exercising
in the heat. Fatigue occurs earlier and is associated with
glycogen depletion (21), whereas carbohydrate supplementa-
tion has been shown to improve exercise capacity in the heat
(11). Exercise in the heat is associated with alterations in
central nervous system function and motor drive, leading to
central fatigue (27, 51). Training and heat acclimatization are
invaluable to athletes who exercise in warm environments.
Knodo and coworkers (35) have described five phenotypic
adaptations to heat: reduced heart rate at a fixed workload,
expanded plasma volume, lower core temperature at an equiv-
alent workload (thus increasing time to fatigue), superior salt
reabsorption from sweat, and an elevated sweat rate. All of
these adaptations contribute to increased exercise performance
in the heat.
Effector Organ Responses to a Decrease in Body
Temperature
Skin blood vessels. When vasoconstriction occurs as a re-
sponse to cold, then blood is shunted away from the skin
surface through the deeper veins. Heat is thus conserved, and
a widening of the gradient between core and peripheral tem-
perature is observed. In response to cold, sympathetic vaso-
constrictor nerves act primarily on -noradrenergic receptors
to cause blood vessel smooth muscle contraction and vasocon-
striction. Other sympathetically released cotransmitters also
contribute to this vasoconstriction, such as ATP and neuropep-
tide Y (see Refs. 9 and 10), the latter of which has been shown
to contribute significantly to cutaneous vascular tone vasocon-
strictor responses to human body cooling (64, 66).
Brown adipose tissue. Brown adipose tissue (BAT) is spe-
cialized for the process of nonshivering thermogenesis, where
oxidative metabolism is uncoupled from ATP production and,
in the process, energy is expended. This tissue is thermogenic
by increasing the metabolic rate. BAT was, until recently,
thought to be only important in small mammals and neonates.
However, evidence for the activation of BAT in adult humans
in response to cold has recently emerged (48, 59, 76), and a
role for BAT in thermoregulation for adults as well as neonates
has become established (75). There is some debate as to
whether this tissue that behaves like BAT is actually true BAT
or is so-called “beige adipose tissue,” which can develop from
white fat cells in response to cold or
3
-adrenergic agonists
(77, 80).
BAT’s potential metabolic role has been recognized to the
extent that it is considered as a potential site for drugs aimed at
altering energy expenditure (73). BAT could potentially be a
therapeutic site for the treatment of obesity. Sympathetic ner-
vous system activity, in response to inputs from peripheral and
central thermoreceptors, can stimulate BAT thermogenesis.
Catecholamines acting on
3
-adrenergic receptors can activate
an uncoupling protein on the inner mitochondrial membrane.
This uncoupling protein, thermogenin, allows H
to cross the
mitochondrial membrane without ATP production. It is known
that sympathetic nervous system activity is increased in the
cold, and nonshivering thermogenesis increases likewise (34).
In addition, BAT thermogenesis can be modulated by a number
of nonthermal factors, including hypoxia, infection, hypogly-
cemia, and psychological stress (42).
Piloerection (goosebumps). The arrector pili muscle is a
small band of smooth muscle that connects the hair follicle to
the connective tissue of the basement membrane in nongla-
borous skin. It is innervated by the autonomic nervous system.
In response to increased sympathetic nerve discharge, the
arrector pili muscles at the base of tiny hairs in the skin
contract and cause the hairs to become upright, trapping air and
thus increasing the insulating layer of air around the body and
minimizing heat loss. This is known as piloerection. As the
muscle contracts, the epidermis buckles, creating “goose-
bumps.” Piloerection is a known reaction to cold and also
strong emotional stimuli. Piloerection is used as an index of
autonomic sympathetic activity and is thought to be mediated
by
1
-adrenergic receptors (1). As humans possess relatively
little hair and are often clothed, heat conservation through
piloerection is usually regarded as insignificant and rudimen-
tary. However, piloerection may become more important in
conjunction with shivering, potentially enhancing the effec-
tiveness of the shivering response (54).
Shivering. When exposed to mild cold, humans will con-
serve heat through mechanisms such as vasoconstriction and
piloerection, which are energetically inexpensive, and by
changes in behavior. If these adjustments are insufficient to
maintain temperature, shivering occurs. The onset of shivering
has been used as an indicator that maximal vasoconstriction
has already been achieved (19). It is initiated by the hypotha-
lamic preoptic area but mediated by the somatic motor cortex
in response to signals from cold receptors in the skin in
particular; therefore, the normal stimulus for shivering is the
skin temperature rather than the core temperature. Shivering
threshold is normally described as the core temperature at
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which shivering is triggered. This is usually related to a given
skin temperature.
Shivering is involuntary, rapid, oscillating contractions of
skeletal muscle. ATP is hydrolyzed, but no work is done
through the contraction, and so the energy produced is released
as heat. In adults, shivering, at its peak, can elicit heat produc-
tion equivalent to five times the basal metabolic rate (20);
however, in neonates, there is a notable absence of shivering
due to the immaturity of their skeletal muscles, and nonshiv-
ering thermogenesis is the most important means by which heat
is generated (67).
Behavioral adaptions to cold. Behavioral thermoregulation
seems to be particularly important in situations where the body
is exposed to extreme cold, where vasoconstriction and
shivering have a limited effect. Recent research suggests
that behavioral control is influenced by many different areas
of the brain: the medulla oblongata, pons, midbrain, somato-
sensory cortex, amygdala, and thermoregulatory centers in
the hypothalamus as well as the prefrontal cortex (for a
review, see Ref. 22).
Transduction of Temperature
Major advances in the transduction processes in peripheral
thermal sensation have been made since the discovery of the
TRP family of ion channels in the last decade and a half. TRP
channels are a superfamily of proteins that can be expressed in
cell membranes and in membranes of internal structures (see
Ref. 81). Many are polymodal in their activation, all resulting
in cation influx. Nine are established as being sensitive to
temperature, and their roles have been extensively reviewed
(12, 60). The classic notion of activation of a thermoreceptive
neuron might describe a rather vague idea of receptor stimu-
lation resulting from a change in intracellular metabolic chem-
ical reactions in proportion to temperature (26). Yet this may
also describe specific subpopulations of temperature receptors
that discriminate cold noxious, cold, warm, and hot noxious
stimuli with overlap between the stimulatory temperatures (see
Fig. 2). Individual TRP channels have now been identified that
may subserve these specific temperature discrimination roles.
Each has a relatively narrow band of temperature activation,
yet overlapping of these sensitivities allows for a wide range of
temperature discrimination. TRPV1 and TRPV2 were among
the first to be identified with temperature sensitivity (13, 14).
They are activated by temperatures higher than 43 and 52°C,
respectively, and may mediate noxious hot sensation. TRPV4
and TRPV3 are activated by temperatures above 25 and 31°C,
likely mediating innocuous warm sensation (63, 78). TRPM8 is
increasingly activated as temperature drops below 27°C and
is likely to mediate innocuous cold sensation (36). TRPA1 is
activated at temperatures below 17°C and may contribute to
noxious cold sensation, although this role is more controver-
sial, as are the roles of TRPM2, TRPM4, and TRPM5 (12, 60).
The role of these TRP channels can now be effectively mapped
onto textbook figures produced before the knowledge of TRP
channels, describing discharge frequencies at different temper-
atures of neurons from these temperature receptors (see Fig. 2).
However, this must be viewed cautiously at present as few
studies have identified these channels as the transduction
mechanisms on primary thermosensitive afferents (46, 60, 65).
Nevertheless, for many (thousands of) years, we have been
aware of chemical agonist stimulation of these channels. We
may be familiar with the cooling sensation of menthol (a
TRPM8 agonist) as we chew our gum or the warming/burning
sensation we experience when eating food spiced with chili
(capcaisin, a TRPV1 agonist).
It is likely that TRP channels are involved in thermal
sensation. They may contribute by direct activation of sensory
fibers; for example, TRPM8 channels are expressed in primary
somatosensory neurons (4). They may also indirectly stimulate
primary sensory fibers; for example, TRPV3 and TRPV4
channels are expressed in abundance in skin keratinocytes,
which may secrete diffusible factors that stimulate sensory
fibers (81). The molecular mechanisms responsible for temper-
ature transduction in the brain, particularly the hypothalamus,
are largely unknown, although the involvement of TRP chan-
nels has not been found to date (see Ref. 47). With regard to
neurons in the preoptic hypothalamus (POA), it has been
proposed that spontaneous activity in their membranes repre-
sents pacemaker activity capable of generating spontaneous
action potentials, and their temperature sensitivity reflects the
temperature sensitivity of these membrane currents (79, 83). It
has been proposed that thermal sensation in the spinal cord
may reflect the activation of TRP channels in the central end of
sensory neurons located in the spinal dorsal horn (45). Tem-
perature transduction mechanisms for receptive neurons that
exist in the viscera (the abdominal blood vessels, esophagus,
and stomach, among other organs) are also less well elucidated.
However, animal studies have revealed that several TRP chan-
nels, similar to the skin afferent nerves, are expressed in
abdominal vagal afferent nerves (82).
Afferent Pathways
Cool and warm temperature information stimulates separate
populations of primary somatosensory afferents in the skin.
These enter the spinal (or trigeminal) dorsal horn to synapse
with second-order ascending neurons in the lamina 1. There are
subtypes of ascending spinothalamic fibers that relay temper-
ature information from the skin to the central nervous system,
and it is likely that fibers carrying information from innocuous
cool or warm receptors provide the majority of the thermoreg-
Freezing
cold
Indiffer-
ent
Burning
hot
Warm
receptors
Cold-receptors
Cold-pain Heat-pain
(TRPA1)
(TRPM8)
(TRPV4 & TRPV3)
(TRPV1 & TRPV2)
5 10 15 20 25 30 35 40 45 50 55 60
10
8
6
4
2
Temperature (°C)
Impulses per second
HotWarmCoolCold
Fig. 2. Discharge frequencies at different skin temperatures of thermorecep-
tors, along with potential transient receptor potential (TRP) channels associ-
ated with receptor function. [Reproduced with permission from Ref. 26.]
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143THERMOREGULATION UPDATE
Advances in Physiology Education doi:10.1152/advan.00126.2014 http://advan.physiology.org
ulatory information rather than those relaying noxious hot or
cold sensations (18).
More recent experiments by Morrison and Nakamura (43,
44) have incorporated labeling of neurons, to delineate projec-
tions, and electrophysiological recordings from the same neu-
rons to examine their responses to peripheral thermal stimula-
tion. They have provided much more detailed information
regarding central projections from the lateral parabrachial nu-
cleus (LPB) where these second-order neurons synapse. The
LPB receives spinal input from cold-sensitive neurons (exter-
nal lateral subnucleus of the LPB) and warm-sensitive neurons
(the dorsal subnucleus of the LBP). Third-order LPB neurons
arise from these regions, which then project to the median
preoptic nucleus (MnPO) of the POA (45, 47). Activation of
these pathways will initiate either heat gain or heat loss
mechanisms (45, 47). Other second-order neurons travel to the
thalamus and then to the cortex to allow conscious sensation of
temperature (Figs. 3 and 4).
Afferents arising in the viscera travel to the central nervous
system mainly in vagus and splanchnic nerves. The majority of
this sensory information, including temperature, converges at
the level of the nucleus tractus solitarius before passing to the
LPB, so the LPB may integrate both skin and visceral thermal
information (45, 47).
Central Control of Thermoregulatory Responses
Previously, temperature control was taught as involving
integration of central and peripheral thermal signals coor-
dinated in the POA and somehow involving a comparison of
this integrated signal with a “set-point” signal. If an error
between the input temperatures and the set point occurs,
then this would trigger appropriate heat gain or heat loss
mechanisms. Although part of this model was based on the
observation of thermal responses to heating and cooling of
the skin and discrete regions of the hypothalamus (26), evi-
dence of the central circuitry necessary for this model has been
+
+
+
+
+
Cool
skin
receptor
Median preoptic nucleus (MnPO) Medial preoptic area (MPO)
Preoptic area of the hypothalamus (POA)
Cerebral
cortex
Thalamus
Dorso-medial
hypothalamus
(DMH)
Rostral raphae
pallidus nuclei
(rRPa)
BAT
Skin
blood
vessel
Skeletal
muscle
++
Lateral
parabrachial
nucleus
(LBP)
Spinal cord
active or
excited neurone
inactive or
inhibited neurone
KEY
PGE2Arachidonic
acid
COX
NSAIDs
Fig. 3. Central circuitry mediating the re-
sponse to cold. POA, preoptic area of the
hypothalamus; MnPO, median preoptic nu-
cleus; MPO, medial preoptic area; DMH, dor-
somedial hypothalamus; rRPa, rostral raphae
pallidus nucleus; LPB, lateral parabrachial nu-
cleus; BAT, brown adipose tissue (after Ref.
45, which also gives details of putative/known
central neurotransmitters in these pathways);
PGE
2
, prostaglandin E
2
. Nonsteroidal anti-
inflammatory drugs (NSAIDs) have an anti-
pyretic affect by inhibiting the enzyme [cy-
clooxygenase (COX)] responsible for produc-
ing PGE
2
.
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144 THERMOREGULATION UPDATE
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lacking. The application of several techniques has allowed
these concepts to be updated. What appears to be emerging is
a model in which an individual set point within the hypothal-
amus is no longer necessary. Evidence is accumulating that
central and peripheral temperatures influence individual effec-
tor circuits independently (45, 47, 57). Thermoreceptive neu-
rons are activated when the appropriate temperature threshold
for that neuron is reached, and action potentials ascend, via
synaptic relays, to the POA. These signals, along with thermo-
receptive signals arising within the POA, act on several effec-
tor outputs, and the influence of central and peripheral signals
varies between different effectors (47, 57). Cold responses, in
general, are more sensitive to skin temperature (potentially
reflecting the preponderance of cold receptors), whereas hot
responses are more sensitive to core temperature [where warm
receptors are more numerous (57)]. Indeed, there are distin-
guishable variations in the sensitivity of specific effector mech-
anisms to skin and core temperature. For example, the shiver-
ing response and BAT activation are the most responsive to
skin temperature compared with the cutaneous circulation
being influenced more by core temperature changes (41).
There is evidence that the individual effector circuits have
distinctly different threshold temperatures. By carefully simul-
taneously recording the neural drive to individual effector
organs, it has been possible to determine a threshold hierarchy
for the activation of each effector (41). For example, activation
of cutaneous sympathetic vasoconstriction occurs slightly be-
fore (higher core temperature) the activation of BAT in rats
(Ref. 53; not confirmed in humans). Yet the contribution of all
the relatively independent individual effector pathways collec-
tively contributes to a steady core temperature of 37°C. In this
way, the concept of the set point has been updated with a more
nuanced model, and the term “balance point” has been pro-
posed as an alternative (57).
The combination of immunohistochemical identification and
other identification techniques, such as the use of c-Fos, along
with electrophysiological recordings from identified neurons
has allowed the identification of neuronal substrates that cor-
+
+
++
+
+
+
+
Warm
skin
receptor
Cerebral
cortex
Thalamus
Dorso-medial
hypothalamus (DMH)
Rostral raphae
pallidus nuclei (rRPa)
BAT
Skin
blood
vessel
Skeletal
muscle
Lateral
parabrachial
nucleus
(LBP)
active or
excited neurone
inactive or
inhibited neurone
KEY
Median preoptic nucleus (MnPO) Medial preoptic area (MPO)
Preoptic area of the hypothalamus (POA)
Fig. 4. Central circuitry mediating the re-
sponses to warm (after Ref. 45).
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145THERMOREGULATION UPDATE
Advances in Physiology Education doi:10.1152/advan.00126.2014 http://advan.physiology.org
roborate this emerging viewpoint from a number of leading
researcher groups in this area (41, 45, 47, 53). The following is
a summary of the control mechanisms for several of the
temperature effector systems that have been elucidated in
recent years. Cold-sensitive neurons within the MnPO are
activated by cutaneous/visceral afferent activity as well as
direct stimulation of MnPO neurons themselves (see Fig. 3).
These activated inhibitory neurons project to the medial pre-
optic hypothalamus. In the case of neural control of blood
vessels, these activated inhibitory neurons reduce activity in
inhibitory projections to the rostral raphae pallidus. Disinhibi-
tion allows full expression of ongoing activity in the sympa-
thetic vasoconstrictor outflow (via the spinal cord and pregan-
glionic and postganglionic sympathetic nerves). Similarly, dis-
inhibition occurs in outflow to skeletal muscle and BAT but at
the level of the dorsomedial hypothalamus, allowing unim-
peded activity in neurons arising in the dorsomedial hypothal-
amus and projecting to these targets via the rostral raphae
pallidus. This induces heat production by shivering in skeletal
muscle and increased metabolism in BAT.
Warm-sensitive neurons within the MnPO are activated by
cutaneous/visceral afferent activity as well as direct stimulation
of MnPO neurons themselves (see Fig. 4). These neurons
project to the medial preoptic hypothalamus, where they acti-
vate inhibitory input that travels to the rostral raphae pallidus
via the dorsal medial hypothalamus (where there may be one
further synapse in the case of outflow to skeletal muscle and
BAT). Finally, this inhibitory signal slows or stops ongoing
activity arising in neurons that project to the spinal cord to
control output to cutaneous blood vessels, BAT, and skeletal
muscle.
Although the importance of the role of active vasodilatation
has been established and several mechanisms by which it may
be achieved have been found, there is still little or no infor-
mation as to the central pathways responsible for its control.
The role of the POA in coordinating the fever response has
been accepted for many years (26). However, in recent years,
further detail of the mechanism of fever has emerged with the
details of the thermoregulatory circuitry outlined above. It is
likely that fever is induced by production of PGE
2
within the
brain in response to various inflammatory mediators, such as
cytokines, that are released as a result of infection. PGE
2
binds
to receptors specifically on warm-sensitive MnPO and medial
preoptic hypothalamus cells within the POA and inhibits their
activity (see Fig. 3). The resultant disinhibition of several
individual pathways for thermoeffectors causes the activation
of shivering and BAT thermogenesis, along with cutaneous
vasoconstriction (45), so that the raised balance point of these
effectors results in heat gain. This contrasts with a vague
notion of a single set point or thermostat simply being turned
up, with no anatomic substrate. Nonsteroidal anti-inflamma-
tory drugs reduce fever by inhibiting the enzymes that are
responsible for the production of prostaglandins (Fig. 3).
It should be emphasised that the majority of the studies that
have allowed the development of these new models of temper-
ature control have been carried out in animals, particularly rats.
The extent to which these models are applicable in humans
remains to be seen. However, the models of thermoregulation
currently in our textbooks similarly rely on conclusions drawn
from animal experimentation, largely because of the impracti-
cality of examining these models in humans.
Conclusions
The major advances in our understanding of thermoregula-
tion are outlined here as follows:
1. On the sensory side, several membrane channel proteins
(TRPs) have been identified that may transduce specific tem-
perature ranges
2. Elucidation of discrete neuroanatomical circuitry for sev-
eral of the thermoregulatory effectors within the hypothalamic
region that updates the concept of the set point
3. Recognition of a potential role for BAT in thermoregu-
lation and metabolism
4. Advances in the understanding of thermoregulatory con-
trol have been paralleled by advances in the mechanisms that
determine vasomotor tone (dilation and constriction), particu-
larly in the roles played by the myriad of vasoactive neu-
rotransmitters, locally released and systemic factors.
This information can be incorporated into current teaching
of thermoregulation to take into account several of the more
recent advances in the field. We anticipate that the overall
teaching would not differ greatly, but that the factual content
would be more up to date. The main conceptual difference is
the replacement of the set-point model with the balance point.
Although the set point has served as an effective and conve-
nient concept to explain central control of core temperature,
particularly in explaining thermoregulatory responses to fever,
we now have a replacement model that is much more firmly
based on experimental data and yet is conceptually no more
complicated.
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the author(s).
AUTHOR CONTRIBUTIONS
Author contributions: E.A.T. and C.D.J. conception and design of research;
E.A.T. and C.D.J. prepared figures; E.A.T. and C.D.J. drafted manuscript;
E.A.T. and C.D.J. edited and revised manuscript; E.A.T. and C.D.J. approved
final version of manuscript.
REFERENCES
1. Alsene KM, Carasso BS, Connors EE, Bakshi VP. Disruption of
prepulse inhibition after stimulation of central but not peripheral -1
adrenergic receptors. Neuropsychopharmacology 31: 2150 –2161, 2006.
2. Armstrong LE, Hubbard RW, Jones BH, Daniels JT. Preparing
Alberto Salazar for the heat of the 1984 Olympic Marathon.Phys
Sportsmed 14: 73– 81, 1986.
3. Bates GP, Miller VS. Sweat rate and sodium loss during work in the heat.
J Occup Med Toxicol 3: 4, 2008.
4. Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI,
Stucky CL, Jordt SE, Julius D. The menthol receptor TRPM8 is the
principal detector of environmental cold. Nature 448: 204 –208, 2007.
5. Best S, Thompson M, Caillaud C, Holvik L. Exercise-heat acclimation
in young and older trained cyclists. J Sci Med Sport 17: 677– 682, 2014.
6. Blair DA, Glover WE, Roddie IC. Vasomotor responses in the human
arm during leg exercise. Circ Res 9: 264 –274, 1960.
7. Boegli Y, Gremion G, Golay S, Kubli S, Liaudet L, Leyvraz PF,
Waeber B, Feihl F. Endurance training enhances vasodilation induced by
nitric oxide in human skin. J Invest Dermatol 121: 1197–1204, 2003.
8. Brade C, Dawson B, Wallman K. Effect of precooling and acclimation
on repeat-sprint performance in heat. J Sports Sci 31: 779 – 86, 2013.
9. Bradley E, Law A, Bell D, Johnson CD. Contributions of cotransmitters
to sympathetically-evoked responses in isolated rat tail artery. Am J
Physiol Heart Circ Physiol 284: H2007–H2014, 2003.
10. Burnstock G. Cotransmission in the autonomic nervous system. Handb
Clin Neurol 117: 23–35, 2013.
Staying Current
146 THERMOREGULATION UPDATE
Advances in Physiology Education doi:10.1152/advan.00126.2014 http://advan.physiology.org
11. Carter J, Jeukendrup AE, Mundel T, Jones DA. Carbohydrate supple-
mentation improves moderate and high-intensity exercise in the heat.
Pflügers Arch 446: 211–219, 2003.
12. Caterina MJ. Transient receptor potential ion channels as participants in
thermosensation and thermoregulation. Am J Physiol Regul Integr Comp
Physiol 292: R64 –R76, 2007.
13. Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D. A capsa-
icin-receptor homologue with a high threshold for noxious heat. Nature
398: 436 – 441, 1999.
14. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD,
Julius D. The capsaicin receptor: a heat-activated ion channel in the pain
pathway. Nature 389: 816 – 824, 1997.
15. Charkoudian N. Skin blood flow in adult human thermoregulation: how
it works, when it does not, and why. Mayo Clin Proc 78: 603– 612, 2003.
16. Clarke S, Parris R, Reynard K. Core-peripheral temperature gradient as
a diagnostic test in dyspnoea. Emerg Med J 22: 633– 635, 2005.
17. Cotter JD, Patterson MJ, Taylor NA. Sweat distribution before and after
repeated heat exposure. Eur J Appl Physiol 76: 181–186, 1997.
18. Craig AD, Krout K, Andrew D. Quatitative response characteristics of
thermoreceptive and nociceptive lamina I spinothalamic neurons in the
cat. J Neurophysiol 86: 1459 –1480, 2001.
19. DeGroot D, Kenney WL. Impaired defense of core temperature in aged
humans during mild cold stress. Am J Physiol Regul Integr Comp Physiol
292: R103–R108, 2007.
20. Eyolfson DA, Tikuisis P, Xu XJ, Weseen G, Giesbrecht GG. Measure-
ment and prediction of peak shivering intensity in humans. Eur J Appl
Physiol 84: 100 –106, 2001.
21. Febbraio MA, Snow RJ, Hargreaves M, Slathis CG, Martin IK, Carey
MF. Muscle metabolism during exercise and heat stress in trained men:
effect of acclimation. J Appl Physiol 76: 589 –597, 1994.
22. Flouris AD. Functional architecture of behavioural thermoregulation. Eur
J Appl Physiol 111: 1– 8, 2011.
23. Galloway SD, Maughan RJ. Effects of ambient temperature on the
capacity to perform prolonged cycle exercise in man. Med Sci Sports
Exerc 9: 1240 –1249, 1997.
24. González-Alonso J, Teller C, Andersen SL, Jensen FB, Hyldig T,
Nielsen B. Influence of body temperature on the development of fatigue
during prolonged exercise in the heat. J Appl Physiol 86: 1032–1039,
1999.
25. Greenfield AD. The circulation through the skin. In: Handbook of Phys-
iology. Circulation. Washington, DC: Am. Physiol. Soc., 1963, sect. 2,
vol. II, chapt. 39, p. 1325–1351.
26. Guyton AC, Hall JE. Textbook of Medical Physiology (13th ed.). Phila-
delphia, PA: Elsevier Saunders, 2011.
27. Hargreaves M. Physiological limits to exercise performance in the heat.
J Sci Med Sport 11: 66 –71, 2008.
28. Höfler W. Changes in regional distribution of sweating during acclima-
tization to heat. J Appl Physiol 25: 503–505, 1968.
29. Holowatz LA, Thompson-Torgerson C, Kenney WL. Aging and the
control of human skin blood flow. Front Biosci 1: 718 –739, 2010.
30. Johnson JM, Kellogg DL Jr. Thermoregulatory and thermal control in
the human cutaneous circulation. Front Biosci 2: 825– 853, 2010.
31. Johnson JM, Minson CT, Kellogg DL. Cutaneous vasodilator and
vasoconstrictor mechanisms in temperature regulation. Compr Physiol 4:
33– 89, 2014.
32. Johnson JM, Pérgola PE, Liao FK, Kellogg DL Jr, Crandall CG. Skin
of the dorsal aspect of human hands and fingers possesses an active
vasodilator system. J Appl Physiol 78: 948 –954, 1995.
33. Kenney WL, Johnson JM. Control of skin blood flow during exercise.
Med Sci Sport Exerc 24: 303–312, 1992.
34. Klingenspor M. Cold-induced recruitment of brown adipose tissue ther-
mogenesis. Exp Physiol 88: 141–148, 2003.
35. Kondo N, Taylor NA, Shibasaki M, Aoki K, Che Muhamed AM.
Thermoregulatory adaptation in humans and its modifying factors. Global
Environ Res 13: 35– 41, 2009.
36. Latorre R, Brauchi S, Madrid R, Orio P. A cool channel in cold
transduction. Physiology 26: 273–285, 2011.
37. Lee JB, Kim TW, Min YK, Yang HM. Long distance runners present
upregulated sweating responses than sedentary counterparts. PLos One 9:
e93976, 2014.
38. Lepock JR. Cellular effects of hyperthermia: relevance to the minimum
dose for thermal damage. Int J Hyperthermia 19: 252–266, 2003.
39. Lorenzo S, Halliwill JR, Sawka MN, Minson CT. Heat acclimation
improves exercise performance. J Appl Physiol 109: 1140 –1147, 2010.
40. Mallet ML. Pathophysiology of accidental hypothermia. Q J Med 95:
775–785, 2002.
41. McAllen RM, Tanaka M, Ootsuka Y, McKinley MJ. Multiple thermo-
regulatory effectors with independent central controls. Eur J Appl Physiol
109: 17–33, 2010.
42. Morrison SF, Madden CJ. Central nervous system regulation of brown
adipose tissue. Comp Physiol 4: 1677–1713, 2014.
43. Morrisson SF, Nakamura K. Preoptic mechanism for cold-defensive
responses to skin cooling. J Physiol 586: 2611–2620, 2008.
44. Morrisson SF, Nakamura K. A thermosensory pathway mediating heat-
defense responses. Proc Natl Acad Sci USA 107: 8848 – 8853, 2010.
45. Morrisson SF, Nakamura K. Central neural pathways for thermoregu-
lation. Front Biosci 16: 74 –104, 2011.
46. Munce TA, Kenney WL. Age-specific modification of local cutaneous
vasodilation by capsaicin-sensitive primary afferents. J Appl Physiol 95:
1016 –1024, 2003.
47. Nakamura K. Central circuities for body temperature regulation and
fever. Am J Physiol Regul Integr Comp Physiol 301: R1207–R1228, 2011.
48. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active
brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab
293: E444 –E452, 2007.
49. Nielsen B, Strange S, Christensen NJ, Warberg J, Saltin B. Acute and
adaptive responses in humans to exercise in a warm, humid environment.
Pflügers Arch 434: 49 –56, 1997.
50. Nielsen TA, da Silver LB, Arendt-Nielsen L, Gazerani P. The effect of
topical capsaicin-induced sensitization of heat-evoked cutaneous vasomo-
tor responses. Int J Physiol Pathophysiol Pharmacol 5: 148 –160, 2013.
51. Nybo L. CNS fatigue provoked by prolonged exercise in the heat. Front
Biosci 2: 779 –792, 2010.
52. Nybo L, Rasmussen P, Sawka MN. Performance in the heat-physiolog-
ical factors of importance for hyperthermia-induced fatigue. Compr
Physiol 4: 657– 689, 2014.
53. Ootsuka Y, McAllen RM. Comparison between two rat sympathetic
pathways activated by cold defense. Am J Physiol Regul Integr Comp
Physiol 291: R589 –R595, 2006.
54. Parsons K. Human Thermal Environments: the Effects of Hot, Moderate,
and Cold Environments on Human Health, Comfort, and Performance
(3rd ed.). Abingdon, UK: Taylor & Francis, 2014.
55. Patterson MJ, Stocks JM, Taylor NA. Humid heat acclimation does not
elicit a preferential sweat redistribution toward the limbs. Am J Physiol
Regul Integr Comp Physiol 286: R512–R518, 2004.
56. Roberts MF, Wenger CB, Stolwijk JA, Nadel ER. Skin blood flow and
sweating changes following exercise training and heat acclimation. J Appl
Physiol 43: 133–137, 1977.
57. Romanovsky AA. Thermoregulation: some concepts have changed. Func-
tional architecture of the thermoregulatory system. Am J Physiol Regul
Integr Comp Physiol 292: R37–R46, 2007.
58. Sato F, Owen M, Matthes R, Sato K, Gisolfi CV. Functional and
morphological changes in the eccrine sweat gland with heat acclimation.
J Appl Physiol 69: 232–236, 1990.
59. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro
T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K,
Kawai Y, Tsujisaki M. High incidence of metabolically active brown
adipose tissue in healthy adult humans: effects of cold exposure and
adiposity. Diabetes 58: 1526 –1531, 2009.
60. Schepers RJ, Ringkamp M. Thermoreceptors and thermosensitive affer-
ents. Neurosci Biobehav Rev 34: 177–184, 2010.
61. Shibasaki M, Crandall CG. Mechanisms and controllers of eccrine
sweating in humans. Front Biosci 2: 685– 696, 2010.
62. Shibasaki M, Wilson TE, Crandall CG. Neural control and mechanisms
of eccrine sweating during heat stress and exercise. J Appl Physiol 100:
1692–1701, 2006.
63. Smith GD, Gunthorpe MJ, Kelsell RE, Hayes PD, Reilly P, Facer P,
Wright JE, Jerman JC, Walhin JP, Oo L, Egerton J, Charles KJ,
Smart D, Randall AD, Anand & Davis JB P. TRPV3 is a temperature-
sensitive vanilloid receptor-like protein. Nature 418: 86 –190, 2002.
64. Stephens DP, Aoki K, Kosiba WA, Johnson JM. Nonnoradrenergic
mechanism of reflex cutaneous vasoconstriction in men. Am J Physiol
Heart Circ Physiol 280: H1496 –H1504, 2001.
65. Stephens DP, Charkoudian N, Benevento JM, Johnson JM, Saumet
JL. The influence of topical capsaicin on the local thermal control of skin
blood flow in humans. Am J Physiol Regul Integr Comp Physiol 281:
R894 –R901, 2001.
Staying Current
147THERMOREGULATION UPDATE
Advances in Physiology Education doi:10.1152/advan.00126.2014 http://advan.physiology.org
66. Stephens DP, Saad AR, Bennett LA, Kosiba WA, Johnson JM.
Neuropeptide Y antagonism reduces reflex cutaneous vasoconstriction in
humans. Am J Physiol Heart Circ Physiol 287: H1404 –H1409, 2004.
67. Stern L. Thermoregulation in the newborn infant: historical, physiological
and clinical considerations. In: Historical Review and Recent Advances in
Neonatal and Perinatal Medicine. Evansville, IN: Mead Johnson Nutri-
tional Division, 1980.
68. Sund-Levander M, Forsberg C, Wahren LK. Normal oral, rectal,
tympanic and axillary body temperature in adult men and women: a
systematic literature review. Scand J Caring Sci 16: 122–128, 2002.
69. Tansey EA, Roe SM, Johnson CJ. The sympathetic release test: a test
used to assess thermoregulation and autonomic control of blood flow. Adv
Physiol Educ 38: 87–92, 2014.
70. Tatterson AJ, Hahn AG, Martini DT, Febbraio MA. Effects of heat
stress on physiological responses and exercise performance in elite cy-
clists. J Sci Med Sport 3: 186 –193, 2000.
71. Taylor NAS, Machado-Moreira CA. Regional variations in transepider-
mal water loss, eccrine sweat gland density, sweat secretion rates and
electrolyte composition in resting and exercising humans. Extrem Physiol
Med 2: 4, 2013.
72. Taylor NA, Machado-Moreira CA, van den Heuvel AM, Caldwell JN.
Hands, and feet: physiological insulators, radiators and evaporators. Eur J
Appl Physiol 114: 2037–2060, 2014.
73. Tseng TH, Cypess AM, Kahn CR. Cellular bioenergetics as a target for
obesity therapy. Nat Rev Drug Discov 9: 465–526, 2010.
74. van Beaumont W, Bullard RW. Sweating: its rapid response to muscular
work. Science 141: 643– 646, 1963.
75. van der Lans AA, Wierts R, Vosselman MJ, Schrauwen P, Brans B,
van Marken Lichtenbelt WD. Cold-activated brown adipose tissue in
human adults–methodological issues. Am J Physiol Regul Integr Comp
Physiol 307: R103–R113, 2014.
76. van der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vossel-
man MJ, Hansen J, Jörgensen JA, Wu J, Mottaghy FM, Schrauwen P,
van Marken Lichtenbelt WD. Cold acclimation recruits human brown
fat and increases nonshivering thermogenesis. J Clin Invest 123: 3395–
3403, 2013.
77. Vitali Murano I A, Zingaretti MC, Frontini A, Ricquier D, Cinti S.
The adipose organ of obesity-prone C57BL/6J mice is composed of mixed
white and brown adipocytes. J Lipid Res 53: 619 – 629, 2012.
78. Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G, Nilius B.
Heat-evoked activation of TRPV4 channels in a HEK293 cell expression
system and in native mouse aorta endothelial cells. J Biol Chem 277:
47044 – 47051, 2002.
79. Wechselberger M, Wright CL, Bishop GL, Boulant JA. Ionic currents
and conductance-based models for hypothalamic neuronal sensitivity. Am
J Physiol Regul Integr Comp Physiol 291: R518 –R529, 2006.
80. Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes:
is beige the new brown? Genes Dev 27: 234 –250, 2013.
81. Wu LJ, Sweet TB, Clapham DE. International Union of Basic and
Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP
ion channel family. Pharmacol Rev 62: 381– 404, 2010.
82. Zhang L, Jones S, Brody K, Costa M, Brookes SJ. Thermo-sensitive
transient receptor potential channels in vagal afferent neurons of the
mouse. Am J Physiol Gastrointest Liver Physiol 286: G983–G991, 2004.
83. Zhao Y, Boulant JA. Temperature effects on neuronal membrane poten-
tials and inward currents in rat hypothalamic tissue slices. J Physiol 564:
245–257, 2005.
Staying Current
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... One of these is the vasomotor mechanism, which changes the caliber of the superficial blood capillaries in the skin to prevent heat exchange with the surrounding medium (69-71). In this case, upon exposure to cold, sympathetic nerve fibers act on α2-adrenergic receptors to generate a vasomotor response that causes smooth muscle vasoconstriction of the superficial blood vessels (72). A study by Bligh et al. (73) used sheep and goats as models to study the effect of intraventricular injections of norepinephrine and acetylcholine on thermoregulatory performance and environmental temperature. ...
... The vital structures in which important metabolic functions are carried out are found in the central parts of the body (17, 18), meaning the heart, lungs, brain, stomach, and kidneys. To protect these systems, when exposed to cold environments or situations that promote heat loss (such as the parturition process and their wet coat), the organism shifts blood supplies from peripheral structures to vital organs (72). Vasoconstriction at peripheral areas such as the thoracic and pelvic limbs, nose and tail prevents heat dissipation and also reduces said structures' superficial temperature (26). ...
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Hypothermia is one factor associated with mortality in newborn ruminants due to the drastic temperature change upon exposure to the extrauterine environment in the first hours after birth. Ruminants are precocial whose mechanisms for generating heat or preventing heat loss involve genetic characteristics, the degree of neurodevelopment at birth and environmental aspects. These elements combine to form a more efficient mechanism than those found in altricial species. Although the degree of neurodevelopment is an important advantage for these species, their greater mobility helps them to search for the udder and consume colostrum after birth. However, anatomical differences such as the distribution of adipose tissue or the presence of type II muscle fibers could lead to the understanding that these species use their energy resources more efficiently for heat production. The introduction of unconventional ruminant species, such as the water buffalo, has led to rethinking other characteristics like the skin thickness or the coat type that could intervene in the thermoregulation capacity of the newborn. Implementing tools to analyze species-specific characteristics that help prevent a critical decline in temperature is deemed a fundamental strategy for avoiding the adverse effects of a compromised thermoregulatory function. Although thermography is a non-invasive method to assess superficial temperature in several non-human animal species, in newborn ruminants there is limited information about its application, making it necessary to discuss the usefulness of this tool. This review aims to analyze the effects of hypothermia in newborn ruminants, their thermoregulation mechanisms that compensate for this condition, and the application of infrared thermography (IRT) to identify cases with hypothermia.
... to cold, mammal's heat production is regulated by changes in motor activity intensity and metabolic heat production by shivering as well as non-shivering thermogenesis, respectively (2). Mammal thermoregulation is under hypothalamic control. ...
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The mouse N. alstoni spontaneously develops the condition of obesity in captivity when fed regular chow. We aim to study the differences in metabolic performance and thermoregulation between adult lean and obese male mice. The experimental approach included indirect calorimetry using metabolic cages for VO 2 intake and VCO 2 production. In contrast, the body temperature was measured and analyzed using intraperitoneal data loggers. It was correlated with the relative presence of UCP1 protein and its gene expression from interscapular adipose tissue (iBAT). We also explored in this tissue the relative presence of Tyrosine Hydroxylase (TH) protein, the rate-limiting enzyme for catecholamine biosynthesis present in iBAT. Results indicate that obese mice show a daily rhythm persists in estimated parameters but with differences in amplitude and profile. Obese mice presented lower body temperature, and a low caloric expenditure, together with lower VO 2 intake and VCO 2 than lean mice. Also, obese mice present a reduced thermoregulatory response after a cold pulse. Results are correlated with a low relative presence of TH and UCP1 protein. However, qPCR analysis of Ucp1 presents an increase in gene expression in iBAT. Histology showed a reduced amount of brown adipocytes in BAT. The aforementioned indicates that the daily rhythm in aerobic metabolism, thermoregulation, and body temperature control have reduced amplitude in obese mice Neotomodon alstoni .
... Skin vascular network (extracted from (61))These two plexuses form a very complex vascular network that serves different purposes, including thermoregulation, nutrition, immune response and intercellular communication(62,63).The vascular endothelium, a monolayer of endothelial cells, forms the anatomical barrier between blood and tissue playing a major role in vascular function. The endothelial cells ensure the circulation and exchange of molecules between blood and interstitial fluid including gases, ions, proteins and also allow the crossing of cells through the phenomenon of diapedesis. ...
Thesis
Hyaluronic acid (HA), a major glycosaminoglycan in the extracellular matrix, plays an important role in a number of biological processes such as wound healing, cancer or embryonic development. The catabolism of HA generates fragments that play a role in migration, apoptosis or immune regulation. HA metabolism is a finely regulated process, adapting its functions to its microenvironment. In the event of deregulation of the metabolism, the accumulation of HA fragments seems to be strongly related to the severity of chronic inflammatory pathologies. Nevertheless, due to its rheological and structural properties, HA prevents dehydration and maintains the structure of the skin. Although it is generally considered to be an inert and biocompatible material, rare cases of late side effects have been observed. Thus, in order to improve our understanding of the mechanisms that can lead to late complications, we hypothesized that the rare complications observed could be related to an inflammatory microenvironment. In this thesis work, we evaluated the inflammatory and vascular potential of degraded and non-degraded HA in dermal cells, immune cells and in a mouse model. In an inflammatory microenvironment, adding HA fragments to endothelial cells and dermal fibroblasts does not worsen the inflammatory response, unlike immune cells. This suggests the involvement of M1 macrophages and mature dendritic cells to a lesser extent in the transmission of inflammation to the tissue. In addition, in a mouse model of chronic low-grade inflammation we showed in vivo that injection of HA can lead to microvascular sensitivity in response to acetylcholine. The hypothesis is that this vascular sensitivity is linked to the recruitment of immune cells at the injection site. Furthermore, we demonstrated in vitro that in the absence of immune cells, an inflammatory vascular microenvironment could lead to an alteration of the extracellular matrix. These results show a diversity in cell-cell interactions depending on the inflammatory degree of the microenvironment, which in the presence of degradation fragments of HA (i.e. during aging or lesion) could weaken the skin tissue
... neurons [14][15][16]. Some of the more recognized channels are the transient receptor potential (TRP) cation channels [7]. Nine channel types play a role in thermoregulation by helping the body discriminate between cold and hot stimuli [10]. ...
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Both rodents and primates have evolved to orchestrate food intake to maintain thermal homeostasis in coping with ambient temperature challenges. However, the mechanisms underlying temperature-coordinated feeding behavior are rarely reported. Here we find that a non-canonical feeding center, the anteroventral and periventricular portions of medial preoptic area (apMPOA) respond to altered dietary states in mice. Two neighboring but distinct neuronal populations in apMPOA mediate feeding behavior by receiving anatomical inputs from external and dorsal subnuclei of lateral parabrachial nucleus. While both populations are glutamatergic, the arcuate nucleus-projecting neurons in apMPOA can sense low temperature and promote food intake. The other type, the paraventricular hypothalamic nucleus (PVH)-projecting neurons in apMPOA are primarily sensitive to high temperature and suppress food intake. Caspase ablation or chemogenetic inhibition of the apMPOA→PVH pathway can eliminate the temperature dependence of feeding. Further projection-specific RNA sequencing and fluorescence in situ hybridization identify that the two neuronal populations are molecularly marked by galanin receptor and apelin receptor. These findings reveal unrecognized cell populations and circuits of apMPOA that orchestrates feeding behavior against thermal challenges.
... External cold stimulation causes vasoconstriction in the cutaneous microvasculature. This response helps maintain a stable core body temperature as the amount of heat transferred from the skin to the core body is decreased due to a substantial reduction in cutaneous blood flow (Charkoudian, 2010;Tansey and Johnson, 2015). In a hyperthermic condition, however, the cutaneous vasoconstriction response to external cold can be a restriction factor because any cooling effect is partly limited to the local region that is directly cooled via conduction. ...
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Hyperthermia impairs physical performance and, when prolonged, results in heat stroke or other illnesses. While extensive research has investigated the effectiveness of various cooling strategies, including cold water immersion and ice-suit, there has been little work focused on overcoming the cutaneous vasoconstriction response to external cold stimulation, which can reduce the effectiveness of these treatments. Over-the-counter (OTC) topical analgesics have been utilized for the treatment of muscle pain for decades; however, to date no research has examined the possibility of taking advantage of their vasodilatory functions in the context of skin cooling. We tested whether an OTC analgesic cream containing 20% methyl salicylate and 6% L-menthol, known cutaneous vasodilators, applied to the skin during skin cooling accelerates heat loss in exercise-induced hyperthermia. Firstly, we found that cutaneous application of OTC topical analgesic cream can attenuate cold-induced vasoconstriction and enhance heat loss during local skin cooling. We also revealed that core body heat loss, as measured by an ingestible telemetry sensor, could be accelerated by cutaneous application of analgesic cream during ice-suit cooling in exercise-induced hyperthermia. A blunted blood pressure response was observed during cooling with the analgesic cream application. Given the safety profile and affordability of topical cutaneous analgesics containing vasodilatory agents, our results suggest that they can be an effective and practical tool for enhancing the cooling effects of skin cooling for hyperthermia.
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Thermosensation has been redefined as an interoceptive modality that provides information about the homeostatic state of the body. However, the contribution of thermosensory signals to the sense of body ownership remains unclear. Across two rubber hand illusion (RHI) experiments (N = 73), we manipulated the visuo-thermal congruency between the felt and seen temperature, on the real and rubber hand respectively. We measured the subjectively experienced RHI, the perceived hand location and temperature of touch, and monitored skin temperature. We found that visuo-thermal incongruencies between the seen and felt touch reduced the subjective and behavioural RHI experience (Experiment 1). Visuo-thermal incongruencies also gave rise to a visuo-thermal illusion effect, but only when the rubber hand was placed in a plausible position (Experiment 2) and when considering individual differences in interoceptive sensibility. Thus, thermosensation contributes to the sense of body ownership by a mechanism of dynamic integration of visual and thermosensory signals. Data from participants engaging in a rubber hand illusion task suggest that thermosensation contributes to the sense of body ownership by dynamically integrating visual and thermosensory signals.
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Background γ-aminobutyric acid (GABA), a common ingredient in sports supplements and other health products, regulates body temperature in the preoptic area and anterior hypothalamus (PO/AH). To date, no study has examined the effect of GABA on thermoregulation during exercise in humans in a cold temperature environment (11 ± 0.3°C, 45% ± 2% relative humidity). Methods We performed a randomized, double-blind study. Ten trained male athletes consumed either a drink (3 ml/kg weight) containing GABA (1,000 mg, trial G) or an equivalent amount of placebo drink (trial C) before exercise. They rested for 20 min and then cycled at 60% of maximum output power for 40 min, pedaling at 60 rpm, and recovered for 20 min. Core temperature (T c ), skin temperature (upper arm, chest, thigh, calf), and heart rate (HR) were monitored at rest (T 0 ), exercise begins (T 20 ), 20 min of exercise (T 40 ), the exercise ends (T 60 ), and at recovery (T 80 ). Results Compared to T 0 , T c decreased significantly at T 20 and increased significantly at T 40 , T 60 and T 80 ( p < 0.01). From 35–80 min, the T c was higher in trial G (peaked at 37.96 ± 0.25°C) than in trial C (37.89 ± 0.37°C), but it failed to reach significant difference ( p > 0.05); T sk continued to increase during exercise and was significantly higher than T 0 at T 40 ( p < 0.05), T 60 and T 80 ( p < 0.01). There was no significant difference in T sk between the two trials ( p > 0.05). Conclusion Our findings provide initial evidence that oral administration of GABA does not affect thermoregulation and has no adverse effects on the body as an ergogenic exercise supplement during exercise in cold environments.
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This article presents a historical overview and an up-to-date review of hyperthermia-induced fatigue during exercise in the heat. Exercise in the heat is associated with a thermoregulatory burden which mediates cardiovascular challenges and influence the cerebral function, increase the pulmonary ventilation, and alter muscle metabolism; which all potentially may contribute to fatigue and impair the ability to sustain power output during aerobic exercise. For maximal intensity exercise, the performance impairment is clearly influenced by cardiovascular limitations to simultaneously support thermoregulation and oxygen delivery to the active skeletal muscle. In contrast, during submaximal intensity exercise at a fixed intensity, muscle blood flow and oxygen consumption remain unchanged and the potential influence from cardiovascular stressing and/or high skin temperature is not related to decreased oxygen delivery to the skeletal muscles. Regardless, performance is markedly deteriorated and exercise-induced hyperthermia is associated with central fatigue as indicated by impaired ability to sustain maximal muscle activation during sustained contractions. The central fatigue appears to be influenced by neurotransmitter activity of the dopaminergic system, but inhibitory signals from thermoreceptors arising secondary to the elevated core, muscle and skin temperatures and augmented afferent feedback from the increased ventilation and the cardiovascular stressing (perhaps baroreceptor sensing of blood pressure stability) and metabolic alterations within the skeletal muscles are likely all factors of importance for afferent feedback to mediate hyperthermia-induced fatigue during submaximal intensity exercise. Taking all the potential factors into account, we propose an integrative model that may help understanding the interplay among factors, but also acknowledging that the influence from a given factor depends on the exercise hyperthermia situation.
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Relatively few studies have investigated peripheral sweating mechanisms of long-distance runners. The aim of this study was to compare peripheral sweating mechanisms in male long-distance runners, and sedentary counterparts. Thirty six subjects, including 20 sedentary controls and 16 long-distance runners (with 7-12 years of athletic training, average 9.2±2.1 years) were observed. Quantitative sudomotor axon reflex testing (QSART) with iontophoresis (2 mA for 5 min) and 10% acetylcholine (ACh) were performed to determine axon reflex-mediated and directly activated (DIR, muscarinic receptor) sweating. Sweat onset time, sweat rate, number of activated sweat glands, sweat output per gland and skin temperature were measured at rest while maximum oxygen uptake (VO2max) were measured during maximal cycling. Sweat rate, activated sweat glands, sweat output per gland, skin temperature and VO2max were significantly higher in the trained runners than in the sedentary controls. Sweat onset time was significantly shorter for the runners. In the group of long-distance runners, significant correlations were found between VO2max and sweat onset time (r2 = 0.543, P<0.01, n = 16), DIR sweat rate (r2 = 0.584, P<0.001, n = 16), sweat output per gland (r2 = 0.539, P<0.01, n = 16). There was no correlation between VO2max and activated sweat glands. These findings suggest that habitual long-distance running results in upregulation of the peripheral sweating mechanisms in humans. Additional research is needed to determine the molecular mechanism underlying these changes. These findings complement the existing sweating data in long-distance runners.
Book
In the ten years since the publication of the second edition of Human Thermal Environments: The Effects of Hot, Moderate, and Cold Environments on Human Health, Comfort, and Performance, Third Edition, the world has embraced electronic communications, making international collaboration almost instantaneous and global. However, there is still a need for a compilation of up-to-date information and best practices. Reflecting current changes in theory and applications, this third edition of a bestseller continues to be the standard text for the design of environments for humans to live and work safely, comfortably, and effectively, and for the design of materials that help people cope with their environments. See What’s New in the Third Edition: • All existing chapters significantly updated • Five new chapters Testing and development of clothing • Adaptive models • Thermal comfort for special populations • Thermal comfort for special environments • Extreme environments • Weather • Outdoor environments and climate change • Fun runs, cold snaps, and heat waves The book covers hot, moderate, and cold environments, and defines them in terms of six basic parameters: air temperature, radiant temperature, humidity, air velocity, clothing worn, and the person’s activity. It focuses on the principles and practice of human response, which incorporates psychology, physiology, and environmental physics with applied ergonomics. The text then discusses water requirements, computer modeling, computer-aided design, and current standards. A systematic treatment of thermal environments and how they affect humans in real-world applications, the book links the health and engineering aspects of the built environment. It provides you with updated tools, techniques, and methods for the design of products and environments that achieve thermal comfort.
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Thermogenesis, the production of heat energy, in brown adipose tissue is a significant component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature in many species from mouse to man and plays a key role in elevating body temperature during the febrile response to infection. The sympathetic neural outflow determining brown adipose tissue (BAT) thermogenesis is regulated by neural networks in the CNS which increase BAT sympathetic nerve activity in response to cutaneous and deep body thermoreceptor signals. Many behavioral states, including wakefulness, immunologic responses, and stress, are characterized by elevations in core body temperature to which central command-driven BAT activation makes a significant contribution. Since energy consumption during BAT thermogenesis involves oxidation of lipid and glucose fuel molecules, the CNS network driving cold-defensive and behavioral state-related BAT activation is strongly influenced by signals reflecting the short- and long-term availability of the fuel molecules essential for BAT metabolism and, in turn, the regulation of BAT thermogenesis in response to metabolic signals can contribute to energy balance, regulation of body adipose stores and glucose utilization. This review summarizes our understanding of the functional organization and neurochemical influences within the CNS networks that modulate the level of BAT sympathetic nerve activity to produce the thermoregulatory and metabolic alterations in BAT thermogenesis and BAT energy expenditure that contribute to overall energy homeostasis and the autonomic support of behavior. © 2014 American Physiological Society. Compr Physiol 4: 1677-1713, 2014.
Article
Blood flow was measured in the hands and forearms of recumbent subjects by venous occlusion plethysmography during leg exer cise on a bicycle ergometer. In three highly practiced subjects, exercise resulted in a small fall in forearm flow and a moderate rise in arterial pressure. Resistance to blood flow was therefore considerably increased. Blocking the vasomotor fibers to forearm skin did not affect this, but blocking the deep nerves to the muscle vessels prevented the increase in vascular resistance during exer cise. Treating the forearm with bretyliurn tosylate had the same effect as deep nerve block. It was concluded that vasoconstrictor tone in muscle is increased during exercise. Since treating the forearm with atropine did not affect the normal response, it was concluded that activation of vasodilator fibers to muscle is not an integral part of the gen eral vasomotor response to exercise. Evidence was also found that the vasodilator outflow to a specific muscle group is not specifically activated when the muscle group in question is exercised. During fairly heavy exercise, vasodilatation occurred in both hand and forearm skin. In the hand this was preceded by vasoconstric tion. Evidence was found that the vasodila tation in the hand was due to release of vaso constrictor tone, whereas that in the forearm was mediated through vasodilator fibers. It is likely that the increase in heat production during exercise was responsible for the reflex vasodilatation in skin.
Article
The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e. close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is [(18)F]FDG-PET/CT-imaging. Dynamic imaging provides quantitative information about glucose uptake rates, while static imaging reflects overall BAT glucose uptake, localization and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET-image, leading to spill over. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [(18)F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the 'fixed volume' methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like MRI or thermography, is discussed.
Article
The purpose of this review is to describe the unique anatomical and physiological features of the hands and feet that support heat conservation and dissipation, and in so doing, highlight the importance of these appendages in human thermoregulation. For instance, the surface area to mass ratio of each hand is 4-5 times greater than that of the body, whilst for each foot, it is ~3 times larger. This characteristic is supported by vascular responses that permit a theoretical maximal mass flow of thermal energy of 6.0 W (136 W m(2)) to each hand for a 1 °C thermal gradient. For each foot, this is 8.5 W (119 W m(2)). In an air temperature of 27 °C, the hands and feet of resting individuals can each dissipate 150-220 W m(2) (male-female) of heat through radiation and convection. During hypothermia, the extremities are physiologically isolated, restricting heat flow to <0.1 W. When the core temperature increases ~0.5 °C above thermoneutral (rest), each hand and foot can sweat at 22-33 mL h(-1), with complete evaporation dissipating 15-22 W (respectively). During heated exercise, sweat flows increase (one hand: 99 mL h(-1); one foot: 68 mL h(-1)), with evaporative heat losses of 67-46 W (respectively). It is concluded that these attributes allow the hands and feet to behave as excellent radiators, insulators and evaporators.