The Dynamics of Eccrine Sweating in Man

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THE DYNAMICS OF ECCRINE SWEATING IN MAN

I. SWEAT DELIVERY THROUGH MYOEPITHELIAL CONTRACTJON* HARRY J. HURLEY, M.D., D.SC.(MED.) AND JOSEPH A. WITKOWSKI, M.D. The functional status of the myoepithelium of30—50 microns in length which invest the secre- the human eccrine sweat gland has long been intory portion of the gland. Myoepithelial cells are question. Unlike the myoepithelium of the apo-not found about the eccrine duet. The composite erine and mammary glands whose expressiveof myoepithelial cells for a single gland is spoken action in the delivery of the secretory product toof as the myoepithelium of that gland. Each the skin surface is now established fact (1, 2), themyoepithelial cell is set within the diaphanous role of the eccrine myoepithelium has never beenbasement membrane of the tubule and is parallel clarified. The literature contains evidence sug-or nearly parallel to its neighbor, the group of gesting the participation of eccrine myoepithelialcells forming a sheet of longitudinally-oriented contraction in sweat delivery principally at lowfibrillar cells. Overall, the myoepithelium runs in rates of sweating (3, 4, 5). During profuse sweat-a slightly spiral fashion, its long axis approxi- ing, the necessity for myoepithelial contractionmating obliquely that of the tubule. is not generally admitted and delivery of sweat Some of the myoepithelial cells may be seen to to the surface is presumed to result from thebranch (fig. 1). Their nuclei are narrow and con- pressure generated from the secretory processform to the overall shape of the cells. Histologi- alone (3). cally, transection of the eccrine tubule may re- In the course of recent investigation of sweatveal the myoepithelial cells as small nipple-like gland function utilizing newly-devised technicsprojections at the base of the secretory cells. employing locally administered dyes excreted byHowever, some of the adjacent tubules usually the ecerine glands (6), we have observed certainshow myoepithelial cells cut obliquely or longi- specialized forms of localized ecerine sweatingtudinally. The myoepithelium is eosinophilic in which provide new evidence for the role of thestaining and can be especially well outlined with myoepithelium in the sweating process. These re-the phosphotungsticacid-hematoxylin and sponses indicate not only an expressive deliveryperiodic acid-Schiff technics, as well as with of sweat to the skin surface as a result of myoepi-silver stains. Glycogen is present in myoepithelial thelial contraction but suggest also that myoepi-cells in modest amounts. They are also strongly thelial contraction is involved with the process ofreactive for sulfhydryl groups and apparently ecerine sweat formation as well. contain alkaline phosphatase (7). Lipid granules, As a preamble to the presentation of our ex-thought to be phospholipids, are found in rows perimental findings, the morphologic features ofalong the long axis of the myoepithelial cells. It the myoepithelium will be reviewed. The readerhas never been clearly established whether the is referred to the excellent and detailed analysesnerves to the sweat glands terminate on the myo- by Rothman (3) and Kuno (4) of the studies inepithelial or secretory cells or supply both struc- the literature which support the statements madetures. above concerning current views of eccrine myo- Myoepithelial cells are seen in both the mam- epithelial function. mary and apocrine sweat glands and, in these glands, are larger than in the eccrine sweat glands. MORPHOLOGY OF THE MYOEPJTHELIUM Except for their smaller size, however, the eccrine The myoepithelial cells of the eccrine sweatmyoepithelial cells are fundamentally identical gland are slender, fibrillar or myoid strands someanatomically to those of the mammary and apocrine glands. *Fromthe Section of Dermatology, Depart- ment of Medicine, Hahnemann Medical College The general consensus is that myoepithelial and Hospital, Philadelphia, Pennsylvania. cells are a variety of smooth muscle, despite their This study was supported by a research grantapparent ectodermal origin. This view is sup- from the National Cystic Fibrosis Research Foundation. ported by the fact that longitudinally-oriented Received for publication December 23, 1961.striae or fibrils similar to those of smooth muscle 329 330 THEJOURNAL OF INVESTIGATIVE DERMATOLOGY S

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Fia. 1A. Human Eccrine Sweat Gland Myoepithelium (Hematoxylin and eosin). The fibrillar nature of the eccrine myoepithelial cells is apparent from the above photomicrograph. Observe the branching of one myoepithelial cell (arrow). More prominent staining of myoepithelial cells is evident after phosphotungstic acid-hematoxylin (Figure 1B). Mag. X 430. in general, are visualized in myoepithelial cellsMaterials and Methods (7, 8). It should be remembered that unlike Fifty-two healthy adult Caucasian and Negro skeletal muscle, which is histologically uniform,males, ranging in age from 20 to 51 years, were smooth muscle represents a diverse group ofused in this study. The skin of the volar forearm myoid tissues whose structure varies according towas used predominantly as the test site in these experiments, although the palm, back, axilla and the special nature of the functions each type per-anterior aspect of the legs were also examined. forms. This structural heterogeneity prevents theAll injections were made through 26 gauge absolute definition of smooth muscle on the basisneedles and the test areas visualized grossly and of anatomic criteria alone. with the aid of a stereoscopic microscope (2—401<). The studies were carried out in a well-ventilated room during all seasons of the year. The room EXPERIMENTAL STUDIES temperature never exceeded 25° C. Humidity The observations to be described were madecontrol was unnecessary since humidity variations possible by the use of newly-developed technicscould not influence these experiments. The dyes of study of sweat gland function using locally-employed were methylene blue (0.5%) and fluores- introduced dyes excreted by the sweat glands (6).cein sodium (5-10%), in physiologic or buffered These technics demand that sweat is newly-formed (phosphate buffer, pH 7.2) saline or distilled or secreted since the excreted dyes are intro-water, pyrogen-free. These dyes were introduced duced into the dermal interstitial space and mustinto the test areas by intradermal injection as be drawn into the glands when they are stimu-previously described (6), and in the case of the lated. Three forms of local stimulation of eccrinefluorescein sodium, also by percutaneous absorp- sweating were employed and will be discussedtion. The latter technic involved the initial light in turn. They are: shaving of the skin area and preparation of a 1. Tissue Distention As Sweating Stimulus "wall" of petrolatum about the test site to con- 2. Local Physical Stimulation Of Eccrinetain the fluorescein sodium which was left on the Sweating skin for 15—30 minutes. A Wood light (TJVL- 3. Special Pharmacologic Stimulants Of Bc-3600A) was used to detect the fluorescent dye in crine Sweating the sweat. Prior to the stimulation of sweating, DYNAMICS OF ECCRINE SWEATING 331 I I A p p 1.4 '4 B. Human Eccrine Sweat Gland Myoepithelium (Phosphotungstic Acid-Hematoxylin stain). Eccrine myoepithelial cells cut in longitudinal and oblique axes are shown (arrows). Coiled appearance or wave- like undulation of several of the myofibrils, possibly indicating contractile activity, is evident at m. Mag. x360. the test areas were covered with a thin film ofstained blue sweat droplets were evident within castor oil or mineral oil* to prevent evaporation3—5 seconds following the injection of the distilled and spreading of the sweat droplets. water. New droplets continued to appear over the next 15—30 seconds. The time of appearance of the 1. Tissue Distention as Sweating Stimulus initial droplets was not coincident with the distention of the dermis as produced by the injection The initial experimental approach involvedbut rather just followed the "recoil" or relaxation attempts to stimulate mechanically the sweatof the tissue subsequent to its distention. Some gland myoepithelium by a distending force in theregression of the size of the droplet or actual dis- dermis. In twenty-five subjects, 0.03 cc. of 0.05%appearance of the smaller droplets could be ob- methylene blue in buffered saline was introducedserved occasionally but not regularly. The re- intradermally into the volar aspect of the forearm.sponse was superior in some subjects and was seen These areas were presumed to be free of activeto involve only the immediate test area (approxi- sweating prior to or at the time of injection ofmately 1.5 cm. in diameter) of the injection wheal dye since immediately adjacent and symmetricalplus a few satellite glands. It should be stressed skin areas were anidrotic as indicated by thethat the droplets seen with this stimulus were Wada modification of the starch-iodine colon-generally smaller than those produced by pilo- metric technic (9). In addition, in some subjectscarpine, physostigmine or thermal stimulation the immediate test area was prepared initially(fig. 2). In some instances, a few blue sweat drop- according to the Wada technic and found to belets were visible even before the injection of the free of any active sweating prior to the followingdistilled water was made. Movement of the needle test. The test area was covered with castor oilbeneath the skin without injection of fluid also and, after an interval of 2—4 minutes, 0.05 cc.would occasionally excite the appearance of a distilled water was then rapidly injected intra-few small blue sweat droplets. dermally at this site. This injection required Under high magnification (30X) and when the 2—3 seconds. response was first evident, it was often possible In all subjects it was observed that tiny, deeply-to discern the blue-stained coiled portion of the * Thelack of autofluorescence of mineral oilsweat duct. Once the sweat droplets increased in made it more desirable for use in the experimentssize, however, this was obscured. in which fluorescein was employed. Twenty-two subjects were then used to conduct 332 THE JOITRNAL OF INVESTIGATIVE DERMATOLOGY p --'I -

C. Human Apoerine Sweat Gland Myoepithelinm (Phosphotungstic Acid-Hematoxylin stain). Well- developed apocrine myoepithelial cells cut in various planes (arrows), are evident in this photomiern- graph. In addition to their greater length, apocrine myoepithelial cells tend to be of greater thickness than do the ecerine myoepithelial cells. Mag. X 360. additional studies of the sweating responses toadministration of 1 cc. of distilled water, it was fluid distention of the dermis. Other fluids, suchnoted that the sweating response soon ceased as isotonic, hypotonic or hypertonic saline,and some blue-stained sweat droplets that had Ringer's solution, 2% procaine solution or addi-appeared initially actually "fell back" or disap- tional dye solution when injected as was the dis-peared during the continuing distention of the tilled water in the above experiments, were alsotissue. Furthermore, when the injection of the found to he capable of eliciting to some degree the distilled water into the test area was made even local sweating response described above. However, more slowly, over a period of 90 seconds, a very the distilled water was decidedly superior to thesepoor or no response was seen. solutions in the production of this response. The preliminary atropinization (atropine sul- Repeat rapid injections of distilled water, atfate, 1:1000) or proeainization (2% procaine) of intervals of two minutes following the initialtest areas so as to prevent axon reflex sweating response, called forth additional similar bursts ofand to produce local anesthesia did not block the blue sweating in the local dye-treated area. Even-local sweating responses to distilled water de- tually, little or no dye was seen in the sweat drop-seribed above. In some instances after atropine, lets produced, however, apparently because ofsome reduction of the sweating response, as com- depletion of the deposit of dye in the tissue. It ispared to the non-atropinized areas, was noted. to be noted that in these experiments, many of the The use of air as the distending force in the sweat droplets present after the initial injectiondennis was also explored. After the injection of of distilled water became larger as subsequentthe methylene blue solution, 1 cc. of air was in- injections prompted additional bursts of sweatingjected rapidly into the test area in a manner in the originally stimulated glands. In addition,analogous to that used with the distilled water. some sweat droplets appeared at the orifices ofIn general this excited the appearance of only a newly activated sweat glands with the latter in-few sweat droplets comparable to a response jections. which might be achieved by the introduction and When the injection of distilled water was mademovement in the dermis of the needle alone. It more slowly, over a period of 20—30 seconds, and was noted that the impact of the air injection the degree of tissue distention increased by theupon the dermis was more diffuse than was that DYNAMICS OF ECCRINE SWEATING 333

ofthe fluid, producing less restricted local tissue distention. Some subcutaneous emphysema was palpable at the end of these experiments, however, indicating that significant quantities of air had been introduced. Similar, hut more striking, sweating responses to those seen after methylene blue were observed using fluorescein sodium introduced by local intradermal injection or by percutaneous absorption. After percutaneous absorption of the dye, almost every sweat gland in the treated area could he seen to respond to the distilled water injection. A more dramatic feature of the fluorescein sodium responses was the frequency that one could observe the tiny, fluorescein-st ained sweat droplets fall hack into the ducts after they were once made to appear from the stimulus of the distilled water or other distending fluid. All of the other sweating responses described V above using methylene blue were also reproduced S with fluorescein sodium. It should he pointed out that methylene blue was also applied percutaneously but it was apparently not absorbed iu significant quantities to stain the sweat droplets heavily enough for ready visualization. A series of experiments were also performed using distilled water as the distending dermal force without preliminary injection of any dye. In order to detect any sweat droplets produced, Wada's iodine-starch in oil colorimetric technic to detect the appearance of sweat was used. It was found that sweat droplets could he made to appear after the injection of distilled water in the absence of any preliminary dye injection. 2. Local Physical Stimulation of Ecceine Sweating In twelve subjects, external mechanical stimulation was applied to skin areas injected with methylene blue or fluorescein sodiuni solutions. For most of these studies, fluorescein sodium was employed since it could be more readily visualized in low concentrations in the sweat. After the introduction of the dye, manual compression (squeezing) or stretching (w'ith release) of the skin resulted in the prompt appearance of dye- stained sw-eat droplets in the treated area in three of the twelve subjects. The droplets were not as Fin. 2A. Eccrine Response, With Excretion ofnumerous as seen after the injection of distilled Methylene Blue, After Physostigmine. After thewater hut were clearly evident) nd appeared preliminary intradermal injection of the test areaonly after these forms of exterimal stimulation of with 0.05% methylene blue solution and coveringthe skin. Simple stroking in a linear fashion with a the test area with mineral oil, 0.03 cc. of 1:1000tongue blade or glass rod over the dye treated physostigmine salicylate was given locally to excite eccrine sweating. Note the large size of thearea did not evoke a response. sweat droplets as compared to those of Figure 2B Preliminary distention of the dye-treated below. Forearm. areas with distilled water, saline or other fluid B. Eccrine Response, With Excretion ofgreatly enhanced the response to compression or Methylene Blue, After Local Distilled Waterstretching of the skin. While sweating occurred Injection. A methylene blue-treated test areainitially as a result of injection of the fluid, once on the forearm received a rapid injection of dis-this response subsided, subsequent physical tilled water. Within 5 seconds, tiny, deeply stainedstimulation of the skin prompted a local sweating blue sweat droplets began to appear in the stimulated zone. The response reached its height withinresponse in eleven of the twelve subjects ex- 15 to 20 seconds, producing the picture shownamined. Repeated compression or stretching of above. The uniformity and very small size of thethe skin resulted in additional bursts of sweating. sw'eat droplets is striking. Procainization of the test areas failed to inhibit 334 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY the eccrine responses to these forms of local physi- compression of the gland by the liquid introduced. cal stimulation although atropiae caused a re-This is an unlikely possibility for several reasons. duction in many subjects. The appearance of the sweat droplets coincided 3. Special Pharmacologic Stimulants of Eccrinewith recoil or relaxation of the tissue and not with Sweating its distention. Moreover, all of the sweat droplets a. Adrenergic Drugs. The local response of thedo not appear simultaneously. After a single in- eccrine sweat glands to epinephrine aud nor-jection, an initial burst appears and involves the epinephrine, in a wide range of concentrations,greatest number of glands, but then additional is well-documented (3, 10). These adrenergicminor bursts with fewer, scattered glands re- drugs can also call forth the excretion of methylene blue in eccrine sweat as do cholinergic drugs,sponding are also seen. If the injected fluid merely thermal and emotional stimuli (11). compressed or forced stored sweat out of the sweat In the present series of experimental studies,glands, such additional bursts would not have the local response of the eccrine sweat glands tooccurred. Furthermore, sweat droplets disap- adreaergic drugs was confirmed and examinedpeared or "fell back" into the ducts as injections further in an additional twenty subjects. The responses seen did not differ from those whichgiven at slower rates were continued. Very slow have already been noted (3, 11) and will not beinjections of fluid into the dermis resulted in a described in detail in this report. poor sweating response even though an equivalent The importance of adrenergic eccrine sweatingor greater amount of distention to that achieved as supportive evidence of myoepithelial fonctionwith rapid injection was seen. Finally, if the in- is considered in greater detail under the Discussion section of this paper. jected fluid simply compressed the sweat gland b. Pitocin. The response of the eccrine sweattubule emptying it of its content, repeat injec- gland to pitocin, the oxytocic principle of thetions of fluid into the dermis should not have posterior pituitary was also examined. It is to beexcited additional bursts of sweating, since the recalled that both the apocrine and mammary myoepithelial cells are known to be responsiveglands would have already been emptied or to this drug (1, 2). collapsed by the compressive force of the injected In seven subjects, doses ranging from 0.01 toliquid. 1.0 International Units of pitocin failed to induce The findings presented herein deserve careful a significant response of colored sweating in dye- treated sites. Subsequent stimulation with dis-analysis in order that they may be properly in- tilled water or pilocarpine of the pitocin-treatedterpreted in terms of sweat gland function. Two glands resulted in the usual sweating response. features of these studies were of special significance. First, there was no other attempt to stimu- usseussiou late concurrently eecrine sweating by any of the Careful consideration has been given to possible standard methods, viz., by drugs, heat or emo- technical or interpretative objections to some oftional. Indeed, as we indicated, no such eeerine the sweating responses we have described. Thesweating was present prior to or coincident with appearance of fluorescein in the sweat dropletsthe experiments. In addition, of course, the sweat- after apparent percutaneous absorption of theing responses to fluid distention of the dermis were dye should be discussed further. The possibilityreproducible in atropinized and anesthetized that the dye, which in those studies, was appliedskin, in which all axon-reflex and sensory re- to the skin surface, might not have really beensponses were blocked and stimulation of the absorbed but simply stained the sweat droplets neuro-effeetor functions apparently prevented. as they appeared at the skin surface, was ex-It is to be noted, however, that in some instances cluded by histologic studies. Frozen sections of a definite reduction, though not complete inhibi- biopsy specimens of these skin areas and examina- tion under fluorescence microscopy demonstratedtion of the response was observed after atropine. localization of the dye in the sweat glands andThus, none of the other clinical stimuli for eeerine adjacent tissues. The staining of the glands wassweating were operative when the sweating re- entirely consistent with what we have observedsponses to dermal distention by fluid occurred. in other studies after intradermal introduction ofSecondly, the injected or percutaneously-ab- the dye (12). In addition, it might be thoughtsorbed dyes were picked up by the sweat gland that the sweating response to injected fluid in theand incorporated in the sweat formed at that very dermis could be explained on the basis of simplemoment. Thus, actual formation of sweat must DYNAMICS OF ECCRINE SWEATING 335 have taken place since the dye had to be drawnglands, such limited stores of sweat would cer- into the gland from the extra-cellular fluid. Thistainly have been depleted with the first response. also occurred in atropinized skin as well as inFinally, as mentioned earlier, histologic studies that which was not atropinized. Obviously then,of the sweat gland indicate that storage of sig- there could have been no storage of pre-formednificant quantities of pre-formed eccrine sweat dye-colored sweat. does not take place. One must conclude therefore In light of these considerations, one must at-that myoepithelial contraction alone, without tempt to reconstruct the possible mechanismsactual concurrent formation of eccrine sweat which could account for the sweating responsescould not account for the responses observed. we observed. Three explanations seem possible: 3. A final possible explanation involves both 1. The injected fluid could have stimulatedthe immediate formation of eccrine sweat and the the eccrine secretory cells to secrete sweat. Thedelivery of the sweat to the skin surface by the secreted sweat might then have gradually filledexpressive force of myoepithelial contraction. As the tubular lumen and flowed out upon the skinhas been discussed thoroughly in the preceding surface without the intervention of any expressivesection and earlier in this report, it is apparent force. Against this possibility was the pulsatilethat in all of the responses observed, formation of or periodic nature of the response—more than onenew sweat must have taken place. The evidence burst of sweating was seen even with a singleindicating myoepithelial contraction resulting in injection. Such intermittency would not be con-sweat delivery may be summarized as follows: sistent with a as€ ri whicb wonid a. T.he natum of the stimuli. fluid dis- be expected to be smooth and continuous. In tention of the dermis and external physical addition, the droplets were often seen to "fall stimulation, for these local responses suggests back" or disappear into the ductal orifice during stimulation of a contractile structure, such as the response, a change remarkably reminiscent the myoepithelium, and not the secretory cells. of the oscillation of sweat levels within microtubes b. The nature of the responses seen, i.e., the inserted in sweat ducts in Takahara's studies small size of the droplets, the intermittency or (13). Such an observation also suggests a pulsatile pulsatile quality of the sweating and the "fall action as might be produced by the relaxation of back" or disappearance into the ductal orifice a contractile structure and not the smooth, con- of the sweat droplets during a response, also tinuing effects of a secretory process. Finally, indicates operation of a contractile mechanism. in the studies with local physical stimulation of Our conclusion, therefore, on the basis of these the skin, the sweating response could hardly befindings and their interpretation as discussed accounted for on the basis of stimulation of theabove, was that the local sweating responses we secretory cells. observed involved both immediate formation of 2. An alternative explanation would be thatnew sweat and myoepithelial contraction, re- the injected fluid and external cutaneous stimula-sulting in expression or delivery of sweat to the tion simply emptied the gland of pre-formedskin surface. Moreover, since the stimuli em- sweat. Numerous objections to this possibilityployed were acting primarily on the myoepi- can be raised, however. On the basis of our com-thelium (and since no other form of stimulation ments earlier regarding the incorporation of theof eccrine sweating was employed concurrently) injected dyes into the sweat, it is clear that actualthe dependency or interrelationship of the process formation of eccrine sweat took place at that time.of sweat formation on this myoepithelial con- It should be noted that the sweat droplets weretraction is postulated also. In other words, in these deeply-tinted and the dye concentration in theresponses the excitation of myoepithelial con- sweat was virtually equivalent, at least visually,traction alone seemed capable of eliciting forma- to that which was injected. Thus, simple stainingtion of sweat as well as the contraction of the of any pre-formed or stored sweat with the dyemyoepithelium with resultant emptying of the was unlikely. Moreover, repeat stimuli with in-gland. In additional studies to be detailed in a jected fluid or external physical stimulation re-later report (14), it has been demonstrated that sulted in additional sweating responses. Even ifthe dye may be seen to appear in the eccrine it were conceded that some storage of small quan-sweat on the skin surface within a very short tities of pre-formed sweat were present in thesetime, as little as 12—15 seconds, following its 336 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY injection intradermally. This indicates that theresponsible for adrenergic eccrine sweating and formation of eccrine sweat, at least as it involvesrecent studies indicate that the same basic mecha- water, these dyes and certain electrolytes, is annisms are operative in adrenergic as in thermal, extremely rapid process and may represent onlycholinergic and other forms of eccrine sweating simple diffusion. In this regard it should be noted(10, 11). While the local response of the eho- that the dyes employed in these studies containlinergically-innervated eccrine sweat glands seems either a Na+ (fluorcsccin sodium) or C1 paradoxical, it may be more readily appreciated (methylene blue choride) ion, the major electro-if one accepts the view that it is precisely because lytic components of eccrine sweat. If the forma-myoepithelial function is essential in the sweating tion of sweat is, at least for water and these con-process that adrenergie drugs can excite an eccrine stituents, a process of simple diffusion, thenresponse. myoepithelial contraction or relaxation might The failure of pitocin, a stimulus of apocrine effect a change in the pore size of the glandularand mammary gland myoepithelium, to induce membrane to allow for the diffusion process. Thisan eccrine response cannot be explained at this speculation requires much additional investiga-time. It is possible that the more delicate eccrine tion, however, and is being examined carefully inmyoepithelium requires much weaker concentra- other studies. It must be stressed that this con-tions of the drug than we employed. Paralysis of cept of diffusion would refer only to sweat forma-the eccrine myoepithelium by pitocin seems un- tion at the level of the secretory coil. It is likelylikely in view of the subsequent response of the that the ultimate composition of the sweat is in-pitocin-treated area to other sweating stimuli. fluenced also by certain activities of the eccrine It is interesting to note that atropine seemed to duct, such as solute reabsorption. rihis latterinhibit, though not completely block, the function is suggested by many findings (3, 15). sweatiug responses to fluid distention of the Extrapolation of the above concepts to otherdermis and to external physical stimulation of the forms of sweating, especially profuse sweatingskin. It should be recalled that the excitation of where no periodicity is observed, is, admittedly,sweating by direct heat, also believed due to not immediately possible. Nevertheless, we feeldirect stimulation of some part of the sweat that our evidence buttresses the already signifi-gland and not related to nervous stimulation, is cant data in the literature (3, 4) which suggestalso partially inhibited by atropine. expressive myoepithelial contraction as the means In view of the importance that might now be for delivery of eccrine sweat to the skin surfaceattached to myoepithelial contractile activity in and that now there can be little question as to thethe process of eccrine sweating, it would be well to role of the myoepithelium in all types of low-gradereexamine some of the unusual aspects of eccrine sweating. As for the problem of profuse sweating,sweat gland physiology that have proved we question the advisability of involving a differ-puzzling. In this regard, the peculiar unrespon- ent mechanism for sweat delivery simply becausesiveness to pharmacologic stimuli of the de- the rate of sweating is increased and would alsonervated ecerine sweat gland and the significance question the validity of assuming no myoepi-of the "refractory period" following adrenergic thelial contractile activity simply because of anstimulation, might more accurately be viewed as absence of periodicity. It seems possible that witheffects of myoepithelial paralysis rather than increased rates of sweating, the periodicity of thedysfunction of the secretory cells. Even the block- response might well disappear or be less evidenting action of atropine on eccrine sweating might even though myoepithelial contraction is still thebe more precisely localized to the myoepithelium responsible expressive force. and not the eccrine secretory cells. In this regard Additional support for the view that delivery ofthe inhibitory or anti-spasmodic action of eccrine sweat to the skin surface occurs as a resultatropine on other forms of smooth muscle, such of myoepithelial contraction may be derived fromas the ureter, bladder, gall-bladder, uterus and the fact that adrenergic drugs can excite localthe gastro-intestinal tract should be recalled (16). eccrine sweating. Epinephrine, it is to be recalled,Finally, the problem of sudomotor tone should be is a classic pharmacologic stimulus for manyconsidered in relation to myoepithelial function. varieties of smooth muscles, including the apo- The superiority of distilled water as a stimulus crine sweat gland myoepithelium. It is not im-of this local sweating response is not immediately plied, however, that a different mechanism isapparent. It could have resulted from the marked DYNAMICS OF ECCRINE SWEATING 337 local irritation distilled water produces. Stimula-of the test areas did not block the local sweating tion of the myoepithelium by the water mightresponses to distilled water, although in some thus have been more readily induced. The possibleinstances, partial inhibition, as compared to non- importance of the hypotonicity of the water as aatropinized sites, was observed. most effective stimulus should also be considered Using a colorimetric technic to detect the ap- although hypotonic saline has not been seen topearance of sweat, it was determined that dis- produce a response superior to that of isotonic ortilled water injections into the dermis could excite hypertonic saline. a local sweating response in the absence of any prior dye injection. SUMMARY AND CONCLUSIONS External cutaneous stimulation in the form of manual compression or stretching with release In this study the excitation of localized eccrinealso induced a local eccrine response in dye- sweating by certain specialized non-nervous andtreated skin areas of 3 of 12 subjects. Preliminary non-pharmacologic stimuli has been described.distention of the dye-treated sites with saline or The findings presented support the concept thatother fluid greatly enhanced the response to such the expressive force of myoepithelial contractionmanual stimulation. Repeated compression or is the mechanism for eccrine sweat delivery to thestretching of the skin resulted in additional bursts skin surface. The studies were made possible byof sweating. the use of newly-devised technics of study of The importance of the phenomenon of adrener- sweat gland function using locally-introducedgic sweating as supportive evidence of myoepi- dyes excreted by the sweat glands. thelial function was discussed. Failure to produce After preliminary intradermal introduction ofan eccrine response with pitocin, in the concen- methylene blue (0.05%) solution or percutaneoustrations employed, was also noted. absorption of fluorescein sodium solution, a local Finally, the evidence presented was discussed eccrine response to distention of the dermis withcritically and an interpretation of the experi- distilled water was consistently produced inmental observations offered. It was concluded twenty-five healthy human volunteers. Tiny,that the most logical explanation for the local deeply-stained droplets were evident within 3—5sweating responses described involved immediate seconds following the injection of the distilledformation of new eccrine sweat and delivery of the water. New droplets continued to appear over thesweat to the skin surface by the expressive force next 15—30 seconds. Some regression of the sizeof myoepithelial contraction. It was postulated of the sweat droplet or its actual disappearance ofthat the formation of eccrine sweat and its de- the droplets could be seen occasionally, especiallylivery to the skin surface as a result of myoepi- when the dye employed was fluorescein sodium. thelial contraction are intimately related and Other fluids such as hypo- or hypertonic saline,coordinated activities. It was suggested further Ringer's solution, 2% procaine or additional dyethat intermittent myoepithelial contraction and solution were also capable of eliciting a similarrelaxation might initiate a process of sweat forma- local response although to a lesser degree and lesstion at the level of the secretory coil, perhaps Consistently than did the distilled water. through simple diffusion, as a result of alteration The injection of air into the dermis failed toof the pore size of the glandular membrane. The excite a significant local eccrine response. rapidity with which new sweat can be formed, as Repeat rapid injections of distilled water, atindicated in these and other studies, supports intervals of two minutes following the initial re-such a theory. sponse, elicited additional bursts of dye-stained REFERENCES sweating, both at sites of previous response and at 1. HURLEY, H. J. AND SHELLEY, W. B.: The role the ductal orifices of newly-activated glands. of the myoepithelium of the human apocrine Eventually, little or no dye was evident in the sweat gland. J. Invest. Derm., 22: 143, 1954. 2. FOLLEY, S. J.: The Physiology and Biochemis- sweat droplets produced, as the local deposit of try of Lactation. London, Olivier and Boyd, dye was depleted. 1956. 3. ROTHMAN, S.: Physiology and Biochemistry Slow injection, over a period of 90 seconds, of of the Skin. Chicago, Ill., Univ. Chicago distilled water into a dye-treated area produced a Press, 1954. . 4.KUNO, YA5: Human Perspiration. Springfield, very poor response or none at all. Ill., Charles C. Thomas Co., 1956. Preliminary atropinization or procainization 5. LoBITz, W. C., JR. AND MASON, H. L.: Chemis- 338 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY

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