Doctor of Philosophy
School of Health Sciences
Machado-Moreira, Christiano Antonio, The regional distribution of human sudomotor function and its neuropharmacological control, Doctor of Philosophy thesis, School of Health Sciences, University of Wollongong, 2011. http://ro.uow.edu.au/theses/3397
In humans, approximately two million eccrine sweat glands are non-uniformly distributed across almost all skin surfaces. The primary function of these cholinergically innervated glands is to subserve thermoregulation, since sweating facilitates evaporative cooling as body temperature increases. Nevertheless, eccrine glands also respond to non-thermal stimulation (e.g. psychological (cognitive task, pain) and exercise stimuli), but the control of these responses and the interactions between thermal and non-thermal sweating are not yet totally understood. Indeed, it is generally regarded that these sudomotor responses are limited to certain skin areas, possibly with separate neural pathways modulating different forms of sweating. However, observations regarding this hypothetical control are equivocal, including the possible functional relevance of adrenergic sweating.
Accordingly, the current research focussed upon the neural control of human sweating, with emphases on the regional distribution and local dynamics of thermallyand non-thermally-induced eccrine secretion, and on the pharmacological nature of these responses. In this regard, a three-phase research project was designed. Firstly, extensive whole-body mappings of both thermal and non-thermal sweating was accomplished (Chapters 2 and 3). In the second phase, individual glands participating in these two forms of sweat were identified at both glabrous and non-glabrous (hairy) skin surfaces (Chapter 4). Finally, the neuropharmacological modulation of thermal and non-thermal sudomotor responses was examined using a systemic cholinergic blockade (Chapter 5).
In a series of six experiments performed in the first phase of this investigation (Chapters 2 and 3), we tested the hypothesis that neither thermal nor non-thermal sweating was restricted to certain skin locations (glabrous or non-glabrous). Furthermore, as detailed information with regard to the regional distribution of sweating within body segments was lacking, and these data are also very useful for thermal modellers, thermal manikin engineers and clothing designers, sweat rates were evaluated from sixty-one distinct sites, representing forty-three regions within six body segments, namely the head, torso, hand, foot, upper and lower limbs.
Initially, thermal sweating was investigated across a wide range of thermal loads, which included passive heating and incremental exercise in the heat. Data from these experiments are presented in Chapter 2, which is formed by four scientific papers. In summary, ventilated sweat capsules were used to measure secretion rates from 43 sites distributed within the head (N=10), torso (N=10), hand (N=10) and foot (N=10). In addition, during experiments reported in Chapter 3, non-thermal sweating (stimuli: cognitive task and painful sensation) was examined at 38 skin sites within six body segments in passively heated subjects (N=30), and from nine surfaces in the thermoneutral state (N=8). In the latter trials, changes in skin conductance were used to measure primary sweating. Studies within this Chapter were also presented in the form of peer-reviewed papers. From this comprehensive sudomotor mapping (Chapters 2 and 3: >60 distinct sites in total), one can unequivocally conclude that sweating is a whole-body phenomenon, regardless of the nature of its stimulation, although secretion is far from being uniformly distributed across the skin, with significant differences observed even within body segments (P<0.05). For instance, thermally induced sweating ranged from 0.37 mg.cm-2.min-1 at the palm to 3.97 mg.cm-2.min-1 at the forehead (averages across the entire experiment; Chapter 2) under identical thermal load. In general, from a regulatory perspective, no evidence seems to exist that supports an hierarchical configuration of sweating across the body surfaces. Indeed, higher secretion rates at any one site would appear to merely reflect that site reaching its potential for evaporative heat loss for the thermal stimulation to which the individual has been exposed. Moreover, during the non-thermal sweat mapping (Chapter 3), the most responsive segments were the head, torso, hand and foot, followed by the arm and forearm, and with the least responsive sites located within the thigh and the leg. Although intra-segmental variations existed within the head, upper limb and hand, these were less evident than those observed during higher intensity (thermal) sweating. Taken together, the present observations challenge the relevance of using an anatomical classification to differentiate between glabrous and non-glabrous (hairy) skin while describing regional differences in sudomotor function, as this generalisation may be too simplistic and imprecise. Furthermore, these data do not support the existence of separate neural pathways for thermal and non-thermal sweating. Therefore, it was hypothesised that a centrally integrated drive would account for the eccrine sudomotor responses, with nerve impulses simultaneously sent to glands across all skin surfaces, and with the regional distribution of sweating possibly resulting from local variations in the sudomotor function.
Accordingly, in subsequent experiments of this investigation, the human sudomotor function was examined at the glandular level (Chapter 4). In particular, we wanted to see if, within a well-defined skin area, the same glands would be recruited during thermal and psychological sweating. Colorimetry and macrophotography were used to evaluate glandular activation at both volar and dorsal surfaces of the hand during passive heating and a cognitive task. From these data, it was evident that large numbers of thermally silent glands became active when a psychological stimulation was superimposed onto thermal sweating (P<0.05; N=10), with these representing over 2,000 glands at the dorsal hand, and more than 14,000 glands at the palm (for each hand). Whilst these additional glands may have been recruited via pathways different from the proven cholinergic modulation of thermal sweating, we interpreted these observations as resulting from the intermittent activation of sweat glands, as previously reported for both thermal and non-thermal sweating, which may be explained by the existence of a spatial summation of multiple synaptic inputs driving the gland response.
Nevertheless, the methods employed in the experiments mentioned above would not allow one to completely rule out the possibility that separate neural pathways existed for the different types of secretion. Indeed, as opposed to the well established cholinergic activation of sweat glands under thermal stimulation, it has been generally regarded that sweating is, at least in part, adrenergically mediated during psychological and exercise stimulations. This hypothesis is intriguing, with considerable supporting evidence, such as the demonstrated presence of adrenergic nerve terminals sparsely distributed around the eccrine glands and the responsiveness of these glands to adrenomimetic agents. Furthermore, the innervation for the eccrine glands is adrenergic in origin, being converted into cholinergic during early development. Finally, the coexpression of cholinergic and adrenergic phenotypes at the sudomotor neuroeffector junction has been recently observed.
Thus, in the final phase of this research, the neuropharmacological modulation of sudomotor responses following thermal, psychological and exercise stimuli was investigated, with sweating from five skin sites evaluated prior to, and following systemic cholinergic blockade (atropine; Chapter 5). In particular, experiments were designed to observe whether or not a systemic cholinergic blockade would fully suppress thermal and non-thermal sweating. Isothermal clamping techniques were used to ensure that the blockade was successfully maintained, as this has not been accomplished in some previous studies available in the literature. In these trials, sweating was abolished at all surfaces ~5 min following the atropine infusion, and secretion could not be re-established by any of the non-thermal stimuli applied. Thus, our data demonstrated that neurally mediated thermal or non-thermal human eccrine sweating is wholly dependent on the neurotransmitter acetylcholine, providing no evidence for a functionally relevant noradrenergic sudomotor pathway (as hypothesised by some), even though sweat glands may respond to catecholamines.
In summary, the present investigation provides detailed information regarding the human sudomotor function, with particular emphasis upon the regional distribution, local dynamics, and neural control of thermal and non-thermal sweating. These data significantly increase our understanding of human thermoregulation in general, and sudomotor control in particular. Indeed, they constitute essential information for both pure and applied physiology (thermal modelling, clothing design, clinical evaluations).