Brain (1992), 115, 1417-1428
THE MECHANISM OF FACIAL SWEATING AND CUTANEOUS VASCULAR RESPONSES TO PAINFUL STIMULATION OF THE EYE by PETER D. DRUMMOND (From the Psychology Section, Murdoch University, Western Australia)
SUMMARY
INTRODUCTION
Irritating the eye causes local reddening, constriction of the pupil, and an increase in intra-ocular pressure (Mandahl and Bill, 1981). Vascular changes in surrounding skin have not been studied. Pain may also induce local sweating. Bickford (1938) and Wilkins et al. (1938) reported that 1—2 min of painful electrical stimulation of the skin produced sweating in a radius of 3 —8 cm around the electrodes. This response required intact postganglionic sympathetic fibres, and was elicited most easily in subjects who were on the verge of sweating, or when the skin was warm. Wilkins et al. (1938) stated that crushing the skin did not produce sweating detectable by the starch-iodine technique, but this method is insensitive to minor fluctuations in sweating. The effect of painful ocular stimulation on blood flow and sweating in surrounding skin was studied in the present experiment. Skin conductance was recorded to detect subtle changes in facial sweating. The nature of the response was studied in normal subjects, and its mechanism was investigated in patients with a unilateral facial nerve lesion compromising parasympathetic outflow. Correspondence to: Dr P. D. Drummond, Psychology Section, Murdoch University, Murdoch, 6150, Western Australia.
© Oxford University Press 1992
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The vascular response in the forehead and cheeks to irritating the eye with soapy water was measured in 15 normal subjects. Electrodermal activity, which reflects sweating, was also measured from both sides of the forehead. The mechanism of the response was studied in 15 patients with a unilateral lesion of the facial nerve blocking parasympathetic outflow. Pulse amplitude usually increased briefly on both sides of the forehead after the soap was placed in the eye; the response persisted for several minutes on the ipsilateral side after the soap had been washed from the eye. A facial nerve lesion blocked the vascular response on the lesioned side to stimulation of either eye. No consistent change in pulse amplitude was recorded from the cheeks, although a response was observed in a few subjects. Electrodermal responses to ocular irritation were generally larger on the ipsilateral than contralateral side of the forehead; in patients with facial palsy, electrodermal responses were greater on the normally innervated side than on the lesioned side. The findings suggest that irritating the eye induces a trigeminal-parasympathetic vasodilator reflex and local sweating. The restricted distribution of the response indicates that separate parasympathetic vasodilator reflexes might operate for each division of the trigeminal nerve.
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METHOD Subjects The normal response to ocular irritation was measured in nine female and six male undergraduate university students aged between 17 yrs and 39 yrs (mean age 21 yrs). The mechanism of the response was investigated in seven males and eight females aged between 31 yrs and 64 yrs (mean age 49 yrs) with unilateral facial palsy produced during removal of an acoustic neuroma 4 - 1 1 mths previously (mean 40 mths). Shortly after the operation each patient had a lateral tarsorrhaphy to protect the cornea from drying. Nine of the 15 patients had noticed some return of lacrimation; in the two patients with the longest history of facial palsy (89 mths and 111 mths) the symptomatic eye now watered more than the opposite eye, particularly in response to gustatory stumuli or sunlight. Schirmer's test confirmed that lacrimation was greater on the symptomatic side in these two cases whereas the eye was dry in the other 13 patients. Each subject provided informed consent for the procedures, which were approved by the university ethics committee.
Data reduction and statistical analysis Pulse amplitude was measured for 30 s before and 60 s after soap was placed in the eye and 1 min and 5 min after washing the soap from the eye. Changes in pulse amplitude were expressed as a percentage of the amplitude recorded immediately before the first eye drop, because the pulse transducer detected only relative changes in cutaneous blood flow. The skin resistance level before placing the drop of soapy water in the eye was used as a baseline. The immediate response to the eye drop was defined as the largest decrease in resistance during the next 30 s. The response during the following 30 s, and levels of skin resistance 1 and 5 min after the soap was washed from the eye, were also measured. Since skin conductance is directly related to sweating whereas skin resistance is inversely related {Lykken and Venables, 1971), values were transformed to conductance units Ots). Skin conductance responses were then calculated as the difference between levels at each data point and the baseline. Separate analyses of variance (MANOVA programme, SPSSX) were computed for responses during stimulation, and return to baseline after the soap was washed from the eye. In normal subjects, comparisons
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Procedures Subjects sat on a comfortable chair in an air-conditioned room maintained at 21±1°C. The forehead and cheeks were cleaned with soap and warm water and dried thoroughly before recording devices were attached. Pulse transducers (photoplethysmographs, Grass Instrument Company, Quincy, MA, USA) were attached with adhesive washers to each side of the forehead, 1 cm above the eyebrows and 4 cm from the midline, and to the cheeks, 3 cm below the eyes and 5 cm from the midline. Pulse amplitude was displayed on a four-channel Grass chart recorder. Electrodermal activity was recorded from each side of the forehead by passing a 10 /tA current between silver-silver chloride electrodes (internal diameter 8 mm), attached by adhesive washers 1 cm above the eyebrows near the midline, and 6 cm from the midline. Skin resistance was detected by two Grass 7P1 preamplifiers in the PGR mode. To eliminate electrical interaction between the two recording sites, at any one instant current was applied on only one side of the forehead. This was achieved by a device which switched between channels 25 times/s. Electrodermal activity was displayed on a two-channel Grass chart recorder. After the subject had been sitting quietly for 15 min, one drop (approximately 0.07 ml) of soapy water was placed in the conjunctival sac of one eye. The soapy water was prepared by mixing 1 ml of liquid bathroom soap in 4 ml of 0.9% saline. In seven patients with a facial nerve lesion, the ipsilateral eye was tested first. Physiological activity was recorded for 1 min, and then the soap was washed out of the eye with 0.9% saline. The subject rated the intensity of pain on a scale ranging from 'not painful' (0) to 'worst pain imaginable' (10). The procedure was repeated for the other eye 5 min later. Facial sweating and flushing to body heating were also investigated in patients with a facial nerve lesion. To induce thermoregulatory responses, warm air from a fan heater was blown under blankets wrapped around the patient. Heating continued for 13 to 44 min (mean 24 min) until facial sweating was visible.
TRIGEMINAL-PAR AS YM PATHETIC REFLEX
1419
were made between the two sides (stimulated versus contralateral), the time course of the response, and between the first and second eye drops. In patients with facial palsy, the response on the lesioned side was compared with the response on the normally innervated side. Saline usually spilled down the cheek when soap was rinsed from the eye. Since this probably influenced vascular activity cheek pulse amplitude data 1 and 5 min after rinsing the soap from the eye were not included in these statistical analyses. RESULTS
Forehead 100 r
Cheeks
T
•timuteted slda contralstaral side
60 r
40
o. c a
20 •
20
0-30 s
31-60 s 1
During
1mln
5mbi After
0-30 8
31-60 8
During
FIG. 1. Vascular responses in the facial skin to ocular irritation. The soapy eye drop induced a persistent response in the ipsilatera] forehead circulation, and a transient response in the contralateral forehead and cheeks. Bars represent the standard error of responses.
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Normal responses to ocular irritation Pain ratings. Ratings ranged between two (mildly painful) and nine (extremely painful), with a mean rating of 5.4 (SD± 1.5). Group and individual ratings were similar for the first and second eye drops. Vascular response. Pulse amplitude increased on both sides of the forehead immediately after the soapy eye drop was administered (Fig. 1). This response persisted on the ipsilateral side of the forehead after the soap was washed from the eye, but not on the contralateral side (Fig. 1). The local vascular response was observed in 14 of 15 subjects; it may be relevant that the face of the unresponsive subject was inflamed by eczema. In general, forehead pulse amplitude increased more on the side ipsilateral to stimulation than on the contralateral side, both during and after stimulation [F(l,14) = 5.76, P < 0.05 and F(l,14) = 9.94, P < 0.01, respectively]. The response was greater during the 30 s after the eye drop was instilled than during the following 30 s [F(l,14) = 21.66, P < 0.001], and gradually subsided from the first to the fifth minute after the soap was washed from the eye [F( 1,14) = 7.95, P < 0.05]. The second drop
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P. D. DRUMMOND
Facial nerve lesion Pain ratings. Most patients with facial palsy reported greater pain on the lesioned side [mean rating 7 ± 2 . 6 compared with 5.5 ±1.5 on the normally innervated side, /(14) = 2.89, P < 0.05]. However, one patient reported less pain on the symptomatic side, and another rated the pain as mild on both sides. O.3
,-. a.
0.2
0.1
5
0.0
I c
-0-1
•timutatad tide contralateral side
-0.2
0-30 8
3 1 -60 6 0 » ""
During
1 mln
5 mln After
FIG. 2. Electrodermal response in the forehead to ocular irritation. Increases in skin conductance 31 —60 s after the soapy eye drop was placed in the eye were slightly larger on the stimulated side than on the contralateral side. In one other patient excluded from analyses, skin conductance increased 8.63 fiS and 0.31 pS on the stimulated side in trials 1 and 2, respectively, and 4.43 fiS and 0.81 /iS on the contralateral side. Bars represent the standard error of responses.
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of soapy water produced a response similar to the first; on the irritated side, pulse amplitude increased 61% to the first eye drop and 65% to the second. In contrast to the forehead, vascular responses in the cheeks did not differ significantly between the stimulated and contralateral sides (Fig. 1). In fact, cheek pulse amplitude did not change consistently from baseline after the soapy eye drop was administered, although a response was observed in a few subjects. Electrodermal response. Skin conductance generally increased slightly on both sides of the forehead after the soapy eye drop was placed in one eye, more so on the stimulated side (Fig. 2). In one unusually responsive subject skin conductance responses to the first eye drop were more than 25 times greater than the mean response in the other 14 subjects; the response was twice as great on the stimulated side. When data from this unusually responsive subject were excluded, the average increase in skin conductance during both eye drops was significantly greater on the stimulated side [F( 1,13) = 14.27, P < 0.01]. The difference in response between the two sides of the forehead was marginally greater 31 — 60 s after the eye drop was instilled than during the first 30 s [F(l,13) = 3.99, P < 0.1]. The second eye drop induced a response similar to the first. After the soap was washed from the eye, skin conductance levels did not differ significantly from baseline on either side of the forehead.
TR1GEMINAL-PARASYMPATHETIC REFLEX
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DISCUSSION
Vascular response to ocular irritation The facial nerve lesion blocked die ipsilateral increase in forehead blood flow normally induced by irritating the eye. Parasympathetic fibres emerging from the brainstem with the facial nerve travel to the geniculate ganglion where they branch off in the greater superficial petrosal (GSP) nerve. The GSP nerve unites with the deep petrosal nerve to form the nerve of the pterygoid canal (Vidian nerve). Parasympathetic fibres are relayed to the sphenopalatine ganglion, which distributes postganglionic fibres to the lacrimal gland (Walsh and Hoyt, 1969), intracranial vessels (Walters et al., 1986), and the vascular supply of the nasal mucosa (Lundblad et al., 1983) and facial skin (Lambert etal., 1984). Gonzalez et al. (1975) reported that electrical stimulation of die ophthalmic division of the trigeminal nerve for 2 —3 min in cats increased forehead temperature by up to 1 °C. This response lasted 6—8 min. When these experiments were repeated by Lambert etal. (1984), most of the response was found to be mediated by a trigeminal-
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Vascular and electrodermal responses to ocular irritation. The facial nerve lesion blocked vascular responses to ocular irritation (Fig. 3). Increases in pulse amplitude were greater on the normally innervated side of the forehead than on the lesioned side both during and after stimulation [F( 1,14) = 17.06, P < 0.001 and F(l,13) = 20.18, P < 0.001, respectively]. The facial nerve lesion also prevented the response to contralateral ocular irritation (Fig. 3). In the eight patients tested, the increase in cheek pulse amplitude was marginally greater on the normally innervated side during ocular irritation (Fig. 4) [F(l,7) = 3.65, P < 0.1]. Baseline levels of skin conductance did not differ significantly between the lesioned and normally innervated sides of the forehead in patients with facial palsy. In general, ipsi- and contralateral increases in skin conductance were greater on the normally innervated side of the forehead than on the lesioned side, both during and after ocular irritation. However, the immediate ipsilateral response to the eye drop was similar on the lesioned and normally innervated sides (Fig. 5). Thus, the difference was greater 31 — 60 s after soap was placed in the eye than during the first 30 s [time by side interaction F(l,14) = 9.61, P < 0.01]. The difference in response between the two sides persisted after the soap was washed from the eye [F(l,13) = 7.26, P < 0.05]. The patient with the longest history of facial palsy showed a different pattern of response to other patients; ocular irritation induced increases in pulse amplitude on both sides of the forehead, and greater increases in skin conductance on the symptomatic side. Thermoregulatory responses. Vascular pulsations increased symmetrically in the forehead and cheeks during body heating (Table 1). Skin conductance recorded from the forehead also increased symmetrically (Table 1). On inspection of the face, sweating was observed on both sides of the forehead (14 patients), cheeks (nine patients), across the upper lip (10 patients) and on the chin (four patients). In one patient less sweat was present on the symptomatic cheek than on the normally innervated cheek although both flushed normally; sensation was also reduced in the symptomatic cheek.
P. D. DRUMMOND
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Ipsilateral Response
Contralateral Response
ao normally innervated side kntonadtide
60 Q.
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-02
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.
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II
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i
1 mln
5 mln After
FIG. 5. Electnxkrmal responses in the forehead to ocular irritation in patients with a facial nerve lesion. The bars represent the standard error of responses.
TABLE I. THERMOREGULATORY RESPONSES IN PATIENTS WITH A FACIAL NERVE LESION Mean response ±SD Lesioned side Innervated side Pulse amplitude (%) Forehead Cheeks Skin conductance (jtS) Forehead
f test
133±73 52±61
128±78 58±69
0.45 0.46
2.77±2.14
2.22±1.71
0.84
parasympathetic vasodilator reflex, with the efferent limb in the GSP nerve. The present findings show for the first time in humans that this reflex is active during minor pain induced by ocular irritation. This supports the view that a trigeminal-parasympathetic reflex mediates some of the extracranial vascular changes during headache and facial pain (Lance et al., 1983). In cats, the trigeminal-parasympathetic reflex employs vasoactive intestinal polypeptide (VIP) as its peripheral neurotransmitter (Goadsby and Macdonald, 1985). The long half-life of VIP (e.g. Lundblad et al., 1983) could explain the persistence of the vascular response after the soap was washed from the eye. The contralateral component of the response could be due to minor crossover of the pathway within the brainstem (Lambert etal., 1984).
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WSrOOOd t M V
-0.4
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P. D. DRUMMOND
Electrodermal response to ocular irritation In normal subjects electrodermal responses to the soapy eye drop were generally larger on the ipsilateral than contralateral side of the forehead. Nordin (1990) reported that bursts of sympathetic traffic in the supraorbital nerve during body heating preceded phasic increases in electrodermal activity in the forehead lasting a few seconds. In contrast, the soapy eye drop generally induced a gradual increase in skin conductance with only a few phasic peaks during the 60 s of stimulation. Unpublished observations in our laboratory on nine patients undergoing stellate ganglion blockade indicated that the soapy
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Lambert et al. (1984) reported that a small proportion of the vascular response to trigeminal stimulation persisted after the trigeminal root had been sectioned, and could have been caused by vasoactive substances released antidromically from sensory nerve endings. Noxious stimulation of the skin produces a local inflammatory response with reddening and wheal formation and a flare in surrounding skin. The flare is mediated by vasoactive substances released from sensory nerve endings near the site of stimulation (Chahl, 1988), probably by an axon reflex which spreads through neighbouring branches of the sensory neuron (Holzer, 1988). Most sensory nerve endings in the cornea and conjunctiva have their cell bodies in the ophthalmic division of the trigeminal ganglion, although the lower eyelid receives fibres from the infraorbital nerve (Williams et al., 1989). Stimulating these nerve endings could produce a flare which spreads to other areas of their receptive field in the forehead and cheeks. However, the absence of response in patients with a facial nerve lesion seems to rule out antidromic activity as an important mediator of the cutaneous response to ocular irritation. Some patients described patchy loss of facial sensation. Nevertheless, the afferent pathway appeared to be grossly intact because all patients reported that the soapy eye drop was at least mildly painful. In fact, pain ratings were greater for the symptomatic eye than for the normally innervated eye, probably because the soap could not be dispersed by blinking or tears. The vascular response was greater in the forehead than in the cheeks. Thus, irritating end-terminals of the ophthalmic nerve produced a vascular response within their cutaneous distribution. In humans, a flush develops after thermocoagulation of the trigeminal ganglion in the distribution of the division coagulated (Drummond et al., 1983); at least part of this response is mediated by antidromic release of vasoactive substances such as calcitonin gene-related peptide from sensory nerve terminals (Goadsby et al., 1988). Gonzalez et al. (1975) reported that stimulating each division of the trigeminal ganglion in cats provoked a rise in temperature which was greater in the cutaneous distribution of that division; furthermore, stimulating discrete points within the brainstem induced increases in facial temperature limited to one trigeminal division. Thus, separate trigeminal-parasympathetic reflexes in each division of the trigeminal nerve might complement antidromic responses. Separate parasympathetic reflexes would be necessary for mediating local vascular responses during lacrimation or salivation. Nordin (1990) reported that active sympathetic vasodilatation increased blood flow in the forehead skin during body heating, arousal and mental stress. Irritating the eye would be expected to cause arousal but, if present, sympathetic vasodilatation was overshadowed by other influences on cutaneous blood flow. Loss of vasodilatation in denervated skin in patients with facial palsy suggests that most of the response was mediated by a trigeminal-parasympathetic reflex.
TRIGEMINAL-PARASYMPATHETIC REFLEX
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Paradoxical lacrimation In two patients with the longest history of facial paralysis, the previously dry eye now watered more than the normally innervated eye, particularly when the patients were eating. In one of these patients the vascular response to ocular irritation was symmetrical, whereas the electrodermal response was greater on the symptomatic side. The syndrome of crocodile tears usually develops after injury to the intracranial portion of the facial nerve, and is attributed to cross-regeneration or cross-stimulation of lacrimal and salivary fibres (Boyer and Gardner, 1949; Chorobski, 1951). In the two patients described above lacrimal fibres may have regenerated because tear flow was generally greater on the symptomatic side. Blood-vessels in the forehead may also have been re-innervated in one case. The excessive electrodermal response in this patient suggests that regenerating vascular or lacrimal fibres had made faulty connections with sweat glands; alternatively, sweat glands could have developed denervation supersensitivity. Thermoregukitory responses in patients with a facial nerve lesion Facial sweating and flushing in response to body heating were symmetrical in patients with a facial nerve lesion (cf List and Peet, 1938). Like thermoregulatory sweating, facial flushing during body heating is mediated by fibres travelling through conventional cervical sympathetic pathways to the face (Drummond and Lance, 1987; Drummond and Finch, 1989; Nordin,1990). Monro (1959) suggested that thermoregulatory sweating in the central mask area of the face could be influenced by outflow through the facial nerve, but this possibility seems remote. The symmetry of thermoregulatory responses in patients with a facial nerve lesion indicates that loss of parasympathetic activity
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eye drop induced the usual tonic increase in skin conductance on the blocked side of the forehead; thus, the response was not mediated by sympathetic outflow. Monro (1959) postulated that the face has an additional sudomotor mechanism. In the auriculotemporal syndrome, pathological gustatory sweating develops after parasympathetic fibres occupy denervated postganglionic sympathetic pathways (Gardner and McCubbin, 1956; Glaister et al., 1958). Monro (1959) suggested that parasympathetic fibres in the facial and glossopharyngeal nerves could take this same route during embryonic development to establish rudimentary connections with facial sweat glands. In contrast to sweat glands in the arms and legs (Janowitz and Grossman, 1950), sympathetically denervated facial sweat glands develop supersensitivity to cholinergic agents (List and Peet, 1938; Salvesen et al, 1988, 1989), possibly because of this extra parasympathetic supply. Parasympathetic fibres might also exert an indirect influence on facial sweating. For example, Stevens and Landis (1987) reported that injection of VIP into rats' paws elicited sweating which was blocked by atropine. Thus, release of VIP from parasympathetic fibres during eye pain might induce sweating. Electrodermal recordings may have been contaminated by electrical activity from the facial muscles or eyes, because small and transient changes could be evoked by voluntarily closing one eye tightly. However, it seems unlikely that paralysis of facial muscles caused the reduction in electrodermal response to the soapy eye drop in patients with a facial nerve lesion, because the reduction persisted for several minutes after the soap had been washed from the eye. Nevertheless, the present findings need to be confirmed using a more direct measure of sweating than electrodermal activity.
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did not increase the effects of sympathetic outflow on the vasculature or sweat glands of the forehead.
ACKNOWLEDGEMENTS I wish to thank Professor B. Stokes for arranging access to his patients, and Professor J. W. Lance and Dr P. J. Goadsby for their constructive suggestions on an early version of this manuscript. This project was supported by grants from the Australian Brain Foundation, the Australian Research Council and Murdoch University. REFERENCES BICKFORD RG (1938) The mechanism of local sweating in response to faradism. Clinical Science, 3, 337-341. BOYER FC, GARDNER WJ (1949) Paroxysmal lacrimation (syndrome of crocodile tears) and its surgical treatment: relation to auriculotemporal syndrome. Archives of Neurology and Psychiatry, Chicago, 61, 5 6 - 6 4 . CHAHL LA (1988) Antidromic vasodHalation and neurogenic inflammation. Pharmacology and Therapeutics, 37, 275-300. CHOROBSKI J (1951) The syndrome of crocodile tears. Archives of Neurology and Psychiatry, Chicago, 65, 299-318. DRUMMOND PD, ANTHONY M (1985) Extracranial vascular responses to sublingual nitroglycerin and oxygen inhalation in cluster headache patients. Headache, 25, 70—74. DRUMMOND PD, FrNCH PM (1989) Reflex control of facial flushing during body heating in man. Brain, 112, 1351-1358. DRUMMOND PD, LANCE JW (1984) Thermographic changes in cluster headache. Neurology, Cleveland, 34, 1292-1298.
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Clinical significance of the findings Painful stimulation of the eye provoked a vascular response in the forehead similar to that observed in some patients during attacks of cluster headache (e.g. fig. 2B, Drummond and Lance, 1984; Drummond and Anthony, 1985). Discharge of the trigeminal nerve during attacks of cluster headache could increase facial blood flow, either by antidromic release of vasoactive agents, or by a trigeminal-parasympathetic reflex. The electrodermal response to ocular irritation is greatly exaggerated in patients with a postganglionic cervical sympathetic lesion, including patients with cluster headache (Drummond and Lance, 1992). Pathological lacrimal sweating could develop after cross-innervation of sweat glands by parasympathetic fibres (van Weerden et al., 1979). This mechanism could mediate paradoxical sweating in sympathetically denervated areas of the face during attacks of cluster headache (Sjaastad et al., 1981). The functional importance of the trigeminal-parasympathetic vasodilator reflex in the skin is uncertain. In intracranial vessels, the reflex could protect the blood supply to the brain during inflammatory states, or may play a role in thermoregulation (Walters et al., 1986). When the eye is irritated, blood flow to the lacrimal gland would need to increase to maintain tear flow. The vascular response might spill over to surrounding skin because the lacrimal gland and lower part of the forehead are both supplied by branches of the ophthalmic artery (Williams et al., 1989). The cutaneous response could also help to remove sources of irritation and begin repair.
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DRUMMOND PD, LANCE JW (1987) Facial flushing and sweating mediated by the sympathetic nervous system. Brain, 110, 7 9 3 - 8 0 3 . DRUMMOND PD, LANCE JW (1992) Pathological sweating and flushing accompanying the trigeminal lacrimal reflex in patients with cluster headache and in patients with a confirmed site of cervical sympathetic deficit: evidence for parasympathetic cross-innervation. Brain, 115, 1429—1445. DRUMMOND PD, GONSKJ A, LANCE JW (1983) Facia] flushing after thermocoagulation of the Gasserian ganglion. Journal of Neurology, Neurosurgery, and Psychiatry, 46, 611—616. GARDNER WJ, MCCUBBIN JW (1956) Auriculotemporal syndrome: gustatory sweating due to misdirection of regenerated nerve fibers. Journal of the American Medical Association, 160, 212—211. GLAISTER DH, HEARNSHAW JR, HEFFRON PF, PECK AW, PATEY DH (1958) The mechanism of
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pattern during spontaneous attacks. Cephalalgia, 1, 233-244. STEVENS LM, LANDIS SC (1987) Development and properties of the secretory response in rat sweat glands: relationship to the induction of cholinergic function in sweat gland innervation. Developmental Biology, 123, 179-190. WALSH FB, HOYT WF (1969) The neurology of lacrimal section. In: Clinical Neuro-ophthalmology, Volume 1. Third edition. By F. B. Walsh and W. F. Hoyt. Baltimore: Williams and Wilkins, pp. 551 - 5 5 5 . WALTERS BB, GILLESPIE SA, MosKowrrz MA (1986) Cerebrovascular projections from the sphenopalatine and otic ganglia to the middle cerebral artery of the cat. Stroke, 17, 488—494.
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post-parotidectomy gustatory sweating (the auriculotemporal syndrome). British Medical Journal, ii, 942-946. GOADSBY PJ, MACDONALD GJ (1985) Extracranial vasodilation mediated by vasoactive intestinal polypeptide (VIP). Brain Research, Amsterdam, 329, 285-288. GOADSBY PJ, EDVINSSON L, EKMAN R (1988) Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Annals of Neurology, 23, 193-1%. GONZALEZ G, ONOFRIO BM, KERR FWL (1975) Vasodilator system for the face. Journal of Neurosurgery, 42, 6 % - 7 0 3 . HOLZER P (1988) Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience, 24, 739 — 768. JANOWITZ HD, GROSSMAN MJ (1950) The response of the sweat glands to some locally acting agents in human subjects. Journal of Investigative Dermatology, 14, 453—458.
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WEERDEN TW VAN, HOUTMAN WA, SCHWEITZER NMJ, MINDERHOUD JM (1979) Lacrimal sweating in
a patient with Raeder's syndrome. Clinical Neurology and Neurosurgcry, 81, 119—121. WILKINS RW, NEWMAN HW, DOUPE J (1938) The local sweat response to faradic stimulation. Brain, 61, 290-297. WILUAMS PL, WARWICK R, DYSON M, BANNISTER LH (1989) Cray's Anatomy. Thirty-seventh edition.
Edinburgh: Churchill Livingstone. {Received December 17, 1991. Revised March 20, 1992. Accepted April 30, 1992)
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THE MECHANISM OF FACIAL SWEATING AND CUTANEOUS VASCULAR RESPONSES TO PAINFUL STIMULATION OF THE EYE by PETER D. DRUMMOND (From the Psychology Section, Murdoch University, Western Australia)
SUMMARY
INTRODUCTION
Irritating the eye causes local reddening, constriction of the pupil, and an increase in intra-ocular pressure (Mandahl and Bill, 1981). Vascular changes in surrounding skin have not been studied. Pain may also induce local sweating. Bickford (1938) and Wilkins et al. (1938) reported that 1—2 min of painful electrical stimulation of the skin produced sweating in a radius of 3 —8 cm around the electrodes. This response required intact postganglionic sympathetic fibres, and was elicited most easily in subjects who were on the verge of sweating, or when the skin was warm. Wilkins et al. (1938) stated that crushing the skin did not produce sweating detectable by the starch-iodine technique, but this method is insensitive to minor fluctuations in sweating. The effect of painful ocular stimulation on blood flow and sweating in surrounding skin was studied in the present experiment. Skin conductance was recorded to detect subtle changes in facial sweating. The nature of the response was studied in normal subjects, and its mechanism was investigated in patients with a unilateral facial nerve lesion compromising parasympathetic outflow. Correspondence to: Dr P. D. Drummond, Psychology Section, Murdoch University, Murdoch, 6150, Western Australia.
© Oxford University Press 1992
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The vascular response in the forehead and cheeks to irritating the eye with soapy water was measured in 15 normal subjects. Electrodermal activity, which reflects sweating, was also measured from both sides of the forehead. The mechanism of the response was studied in 15 patients with a unilateral lesion of the facial nerve blocking parasympathetic outflow. Pulse amplitude usually increased briefly on both sides of the forehead after the soap was placed in the eye; the response persisted for several minutes on the ipsilateral side after the soap had been washed from the eye. A facial nerve lesion blocked the vascular response on the lesioned side to stimulation of either eye. No consistent change in pulse amplitude was recorded from the cheeks, although a response was observed in a few subjects. Electrodermal responses to ocular irritation were generally larger on the ipsilateral than contralateral side of the forehead; in patients with facial palsy, electrodermal responses were greater on the normally innervated side than on the lesioned side. The findings suggest that irritating the eye induces a trigeminal-parasympathetic vasodilator reflex and local sweating. The restricted distribution of the response indicates that separate parasympathetic vasodilator reflexes might operate for each division of the trigeminal nerve.
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METHOD Subjects The normal response to ocular irritation was measured in nine female and six male undergraduate university students aged between 17 yrs and 39 yrs (mean age 21 yrs). The mechanism of the response was investigated in seven males and eight females aged between 31 yrs and 64 yrs (mean age 49 yrs) with unilateral facial palsy produced during removal of an acoustic neuroma 4 - 1 1 mths previously (mean 40 mths). Shortly after the operation each patient had a lateral tarsorrhaphy to protect the cornea from drying. Nine of the 15 patients had noticed some return of lacrimation; in the two patients with the longest history of facial palsy (89 mths and 111 mths) the symptomatic eye now watered more than the opposite eye, particularly in response to gustatory stumuli or sunlight. Schirmer's test confirmed that lacrimation was greater on the symptomatic side in these two cases whereas the eye was dry in the other 13 patients. Each subject provided informed consent for the procedures, which were approved by the university ethics committee.
Data reduction and statistical analysis Pulse amplitude was measured for 30 s before and 60 s after soap was placed in the eye and 1 min and 5 min after washing the soap from the eye. Changes in pulse amplitude were expressed as a percentage of the amplitude recorded immediately before the first eye drop, because the pulse transducer detected only relative changes in cutaneous blood flow. The skin resistance level before placing the drop of soapy water in the eye was used as a baseline. The immediate response to the eye drop was defined as the largest decrease in resistance during the next 30 s. The response during the following 30 s, and levels of skin resistance 1 and 5 min after the soap was washed from the eye, were also measured. Since skin conductance is directly related to sweating whereas skin resistance is inversely related {Lykken and Venables, 1971), values were transformed to conductance units Ots). Skin conductance responses were then calculated as the difference between levels at each data point and the baseline. Separate analyses of variance (MANOVA programme, SPSSX) were computed for responses during stimulation, and return to baseline after the soap was washed from the eye. In normal subjects, comparisons
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Procedures Subjects sat on a comfortable chair in an air-conditioned room maintained at 21±1°C. The forehead and cheeks were cleaned with soap and warm water and dried thoroughly before recording devices were attached. Pulse transducers (photoplethysmographs, Grass Instrument Company, Quincy, MA, USA) were attached with adhesive washers to each side of the forehead, 1 cm above the eyebrows and 4 cm from the midline, and to the cheeks, 3 cm below the eyes and 5 cm from the midline. Pulse amplitude was displayed on a four-channel Grass chart recorder. Electrodermal activity was recorded from each side of the forehead by passing a 10 /tA current between silver-silver chloride electrodes (internal diameter 8 mm), attached by adhesive washers 1 cm above the eyebrows near the midline, and 6 cm from the midline. Skin resistance was detected by two Grass 7P1 preamplifiers in the PGR mode. To eliminate electrical interaction between the two recording sites, at any one instant current was applied on only one side of the forehead. This was achieved by a device which switched between channels 25 times/s. Electrodermal activity was displayed on a two-channel Grass chart recorder. After the subject had been sitting quietly for 15 min, one drop (approximately 0.07 ml) of soapy water was placed in the conjunctival sac of one eye. The soapy water was prepared by mixing 1 ml of liquid bathroom soap in 4 ml of 0.9% saline. In seven patients with a facial nerve lesion, the ipsilateral eye was tested first. Physiological activity was recorded for 1 min, and then the soap was washed out of the eye with 0.9% saline. The subject rated the intensity of pain on a scale ranging from 'not painful' (0) to 'worst pain imaginable' (10). The procedure was repeated for the other eye 5 min later. Facial sweating and flushing to body heating were also investigated in patients with a facial nerve lesion. To induce thermoregulatory responses, warm air from a fan heater was blown under blankets wrapped around the patient. Heating continued for 13 to 44 min (mean 24 min) until facial sweating was visible.
TRIGEMINAL-PAR AS YM PATHETIC REFLEX
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were made between the two sides (stimulated versus contralateral), the time course of the response, and between the first and second eye drops. In patients with facial palsy, the response on the lesioned side was compared with the response on the normally innervated side. Saline usually spilled down the cheek when soap was rinsed from the eye. Since this probably influenced vascular activity cheek pulse amplitude data 1 and 5 min after rinsing the soap from the eye were not included in these statistical analyses. RESULTS
Forehead 100 r
Cheeks
T
•timuteted slda contralstaral side
60 r
40
o. c a
20 •
20
0-30 s
31-60 s 1
During
1mln
5mbi After
0-30 8
31-60 8
During
FIG. 1. Vascular responses in the facial skin to ocular irritation. The soapy eye drop induced a persistent response in the ipsilatera] forehead circulation, and a transient response in the contralateral forehead and cheeks. Bars represent the standard error of responses.
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Normal responses to ocular irritation Pain ratings. Ratings ranged between two (mildly painful) and nine (extremely painful), with a mean rating of 5.4 (SD± 1.5). Group and individual ratings were similar for the first and second eye drops. Vascular response. Pulse amplitude increased on both sides of the forehead immediately after the soapy eye drop was administered (Fig. 1). This response persisted on the ipsilateral side of the forehead after the soap was washed from the eye, but not on the contralateral side (Fig. 1). The local vascular response was observed in 14 of 15 subjects; it may be relevant that the face of the unresponsive subject was inflamed by eczema. In general, forehead pulse amplitude increased more on the side ipsilateral to stimulation than on the contralateral side, both during and after stimulation [F(l,14) = 5.76, P < 0.05 and F(l,14) = 9.94, P < 0.01, respectively]. The response was greater during the 30 s after the eye drop was instilled than during the following 30 s [F(l,14) = 21.66, P < 0.001], and gradually subsided from the first to the fifth minute after the soap was washed from the eye [F( 1,14) = 7.95, P < 0.05]. The second drop
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P. D. DRUMMOND
Facial nerve lesion Pain ratings. Most patients with facial palsy reported greater pain on the lesioned side [mean rating 7 ± 2 . 6 compared with 5.5 ±1.5 on the normally innervated side, /(14) = 2.89, P < 0.05]. However, one patient reported less pain on the symptomatic side, and another rated the pain as mild on both sides. O.3
,-. a.
0.2
0.1
5
0.0
I c
-0-1
•timutatad tide contralateral side
-0.2
0-30 8
3 1 -60 6 0 » ""
During
1 mln
5 mln After
FIG. 2. Electrodermal response in the forehead to ocular irritation. Increases in skin conductance 31 —60 s after the soapy eye drop was placed in the eye were slightly larger on the stimulated side than on the contralateral side. In one other patient excluded from analyses, skin conductance increased 8.63 fiS and 0.31 pS on the stimulated side in trials 1 and 2, respectively, and 4.43 fiS and 0.81 /iS on the contralateral side. Bars represent the standard error of responses.
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of soapy water produced a response similar to the first; on the irritated side, pulse amplitude increased 61% to the first eye drop and 65% to the second. In contrast to the forehead, vascular responses in the cheeks did not differ significantly between the stimulated and contralateral sides (Fig. 1). In fact, cheek pulse amplitude did not change consistently from baseline after the soapy eye drop was administered, although a response was observed in a few subjects. Electrodermal response. Skin conductance generally increased slightly on both sides of the forehead after the soapy eye drop was placed in one eye, more so on the stimulated side (Fig. 2). In one unusually responsive subject skin conductance responses to the first eye drop were more than 25 times greater than the mean response in the other 14 subjects; the response was twice as great on the stimulated side. When data from this unusually responsive subject were excluded, the average increase in skin conductance during both eye drops was significantly greater on the stimulated side [F( 1,13) = 14.27, P < 0.01]. The difference in response between the two sides of the forehead was marginally greater 31 — 60 s after the eye drop was instilled than during the first 30 s [F(l,13) = 3.99, P < 0.1]. The second eye drop induced a response similar to the first. After the soap was washed from the eye, skin conductance levels did not differ significantly from baseline on either side of the forehead.
TR1GEMINAL-PARASYMPATHETIC REFLEX
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DISCUSSION
Vascular response to ocular irritation The facial nerve lesion blocked die ipsilateral increase in forehead blood flow normally induced by irritating the eye. Parasympathetic fibres emerging from the brainstem with the facial nerve travel to the geniculate ganglion where they branch off in the greater superficial petrosal (GSP) nerve. The GSP nerve unites with the deep petrosal nerve to form the nerve of the pterygoid canal (Vidian nerve). Parasympathetic fibres are relayed to the sphenopalatine ganglion, which distributes postganglionic fibres to the lacrimal gland (Walsh and Hoyt, 1969), intracranial vessels (Walters et al., 1986), and the vascular supply of the nasal mucosa (Lundblad et al., 1983) and facial skin (Lambert etal., 1984). Gonzalez et al. (1975) reported that electrical stimulation of die ophthalmic division of the trigeminal nerve for 2 —3 min in cats increased forehead temperature by up to 1 °C. This response lasted 6—8 min. When these experiments were repeated by Lambert etal. (1984), most of the response was found to be mediated by a trigeminal-
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Vascular and electrodermal responses to ocular irritation. The facial nerve lesion blocked vascular responses to ocular irritation (Fig. 3). Increases in pulse amplitude were greater on the normally innervated side of the forehead than on the lesioned side both during and after stimulation [F( 1,14) = 17.06, P < 0.001 and F(l,13) = 20.18, P < 0.001, respectively]. The facial nerve lesion also prevented the response to contralateral ocular irritation (Fig. 3). In the eight patients tested, the increase in cheek pulse amplitude was marginally greater on the normally innervated side during ocular irritation (Fig. 4) [F(l,7) = 3.65, P < 0.1]. Baseline levels of skin conductance did not differ significantly between the lesioned and normally innervated sides of the forehead in patients with facial palsy. In general, ipsi- and contralateral increases in skin conductance were greater on the normally innervated side of the forehead than on the lesioned side, both during and after ocular irritation. However, the immediate ipsilateral response to the eye drop was similar on the lesioned and normally innervated sides (Fig. 5). Thus, the difference was greater 31 — 60 s after soap was placed in the eye than during the first 30 s [time by side interaction F(l,14) = 9.61, P < 0.01]. The difference in response between the two sides persisted after the soap was washed from the eye [F(l,13) = 7.26, P < 0.05]. The patient with the longest history of facial palsy showed a different pattern of response to other patients; ocular irritation induced increases in pulse amplitude on both sides of the forehead, and greater increases in skin conductance on the symptomatic side. Thermoregulatory responses. Vascular pulsations increased symmetrically in the forehead and cheeks during body heating (Table 1). Skin conductance recorded from the forehead also increased symmetrically (Table 1). On inspection of the face, sweating was observed on both sides of the forehead (14 patients), cheeks (nine patients), across the upper lip (10 patients) and on the chin (four patients). In one patient less sweat was present on the symptomatic cheek than on the normally innervated cheek although both flushed normally; sensation was also reduced in the symptomatic cheek.
P. D. DRUMMOND
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Ipsilateral Response
Contralateral Response
ao normally innervated side kntonadtide
60 Q.
b 0.0
0.0
1
< V
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-02
-02
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nofmeJty
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0-30 s
31-60 8"
1
-0.4
1 min
During
5 mln
After
.
0-30»
...
II
31-60»"
During
i
1 mln
5 mln After
FIG. 5. Electnxkrmal responses in the forehead to ocular irritation in patients with a facial nerve lesion. The bars represent the standard error of responses.
TABLE I. THERMOREGULATORY RESPONSES IN PATIENTS WITH A FACIAL NERVE LESION Mean response ±SD Lesioned side Innervated side Pulse amplitude (%) Forehead Cheeks Skin conductance (jtS) Forehead
f test
133±73 52±61
128±78 58±69
0.45 0.46
2.77±2.14
2.22±1.71
0.84
parasympathetic vasodilator reflex, with the efferent limb in the GSP nerve. The present findings show for the first time in humans that this reflex is active during minor pain induced by ocular irritation. This supports the view that a trigeminal-parasympathetic reflex mediates some of the extracranial vascular changes during headache and facial pain (Lance et al., 1983). In cats, the trigeminal-parasympathetic reflex employs vasoactive intestinal polypeptide (VIP) as its peripheral neurotransmitter (Goadsby and Macdonald, 1985). The long half-life of VIP (e.g. Lundblad et al., 1983) could explain the persistence of the vascular response after the soap was washed from the eye. The contralateral component of the response could be due to minor crossover of the pathway within the brainstem (Lambert etal., 1984).
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WSrOOOd t M V
-0.4
\
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P. D. DRUMMOND
Electrodermal response to ocular irritation In normal subjects electrodermal responses to the soapy eye drop were generally larger on the ipsilateral than contralateral side of the forehead. Nordin (1990) reported that bursts of sympathetic traffic in the supraorbital nerve during body heating preceded phasic increases in electrodermal activity in the forehead lasting a few seconds. In contrast, the soapy eye drop generally induced a gradual increase in skin conductance with only a few phasic peaks during the 60 s of stimulation. Unpublished observations in our laboratory on nine patients undergoing stellate ganglion blockade indicated that the soapy
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Lambert et al. (1984) reported that a small proportion of the vascular response to trigeminal stimulation persisted after the trigeminal root had been sectioned, and could have been caused by vasoactive substances released antidromically from sensory nerve endings. Noxious stimulation of the skin produces a local inflammatory response with reddening and wheal formation and a flare in surrounding skin. The flare is mediated by vasoactive substances released from sensory nerve endings near the site of stimulation (Chahl, 1988), probably by an axon reflex which spreads through neighbouring branches of the sensory neuron (Holzer, 1988). Most sensory nerve endings in the cornea and conjunctiva have their cell bodies in the ophthalmic division of the trigeminal ganglion, although the lower eyelid receives fibres from the infraorbital nerve (Williams et al., 1989). Stimulating these nerve endings could produce a flare which spreads to other areas of their receptive field in the forehead and cheeks. However, the absence of response in patients with a facial nerve lesion seems to rule out antidromic activity as an important mediator of the cutaneous response to ocular irritation. Some patients described patchy loss of facial sensation. Nevertheless, the afferent pathway appeared to be grossly intact because all patients reported that the soapy eye drop was at least mildly painful. In fact, pain ratings were greater for the symptomatic eye than for the normally innervated eye, probably because the soap could not be dispersed by blinking or tears. The vascular response was greater in the forehead than in the cheeks. Thus, irritating end-terminals of the ophthalmic nerve produced a vascular response within their cutaneous distribution. In humans, a flush develops after thermocoagulation of the trigeminal ganglion in the distribution of the division coagulated (Drummond et al., 1983); at least part of this response is mediated by antidromic release of vasoactive substances such as calcitonin gene-related peptide from sensory nerve terminals (Goadsby et al., 1988). Gonzalez et al. (1975) reported that stimulating each division of the trigeminal ganglion in cats provoked a rise in temperature which was greater in the cutaneous distribution of that division; furthermore, stimulating discrete points within the brainstem induced increases in facial temperature limited to one trigeminal division. Thus, separate trigeminal-parasympathetic reflexes in each division of the trigeminal nerve might complement antidromic responses. Separate parasympathetic reflexes would be necessary for mediating local vascular responses during lacrimation or salivation. Nordin (1990) reported that active sympathetic vasodilatation increased blood flow in the forehead skin during body heating, arousal and mental stress. Irritating the eye would be expected to cause arousal but, if present, sympathetic vasodilatation was overshadowed by other influences on cutaneous blood flow. Loss of vasodilatation in denervated skin in patients with facial palsy suggests that most of the response was mediated by a trigeminal-parasympathetic reflex.
TRIGEMINAL-PARASYMPATHETIC REFLEX
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Paradoxical lacrimation In two patients with the longest history of facial paralysis, the previously dry eye now watered more than the normally innervated eye, particularly when the patients were eating. In one of these patients the vascular response to ocular irritation was symmetrical, whereas the electrodermal response was greater on the symptomatic side. The syndrome of crocodile tears usually develops after injury to the intracranial portion of the facial nerve, and is attributed to cross-regeneration or cross-stimulation of lacrimal and salivary fibres (Boyer and Gardner, 1949; Chorobski, 1951). In the two patients described above lacrimal fibres may have regenerated because tear flow was generally greater on the symptomatic side. Blood-vessels in the forehead may also have been re-innervated in one case. The excessive electrodermal response in this patient suggests that regenerating vascular or lacrimal fibres had made faulty connections with sweat glands; alternatively, sweat glands could have developed denervation supersensitivity. Thermoregukitory responses in patients with a facial nerve lesion Facial sweating and flushing in response to body heating were symmetrical in patients with a facial nerve lesion (cf List and Peet, 1938). Like thermoregulatory sweating, facial flushing during body heating is mediated by fibres travelling through conventional cervical sympathetic pathways to the face (Drummond and Lance, 1987; Drummond and Finch, 1989; Nordin,1990). Monro (1959) suggested that thermoregulatory sweating in the central mask area of the face could be influenced by outflow through the facial nerve, but this possibility seems remote. The symmetry of thermoregulatory responses in patients with a facial nerve lesion indicates that loss of parasympathetic activity
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eye drop induced the usual tonic increase in skin conductance on the blocked side of the forehead; thus, the response was not mediated by sympathetic outflow. Monro (1959) postulated that the face has an additional sudomotor mechanism. In the auriculotemporal syndrome, pathological gustatory sweating develops after parasympathetic fibres occupy denervated postganglionic sympathetic pathways (Gardner and McCubbin, 1956; Glaister et al., 1958). Monro (1959) suggested that parasympathetic fibres in the facial and glossopharyngeal nerves could take this same route during embryonic development to establish rudimentary connections with facial sweat glands. In contrast to sweat glands in the arms and legs (Janowitz and Grossman, 1950), sympathetically denervated facial sweat glands develop supersensitivity to cholinergic agents (List and Peet, 1938; Salvesen et al, 1988, 1989), possibly because of this extra parasympathetic supply. Parasympathetic fibres might also exert an indirect influence on facial sweating. For example, Stevens and Landis (1987) reported that injection of VIP into rats' paws elicited sweating which was blocked by atropine. Thus, release of VIP from parasympathetic fibres during eye pain might induce sweating. Electrodermal recordings may have been contaminated by electrical activity from the facial muscles or eyes, because small and transient changes could be evoked by voluntarily closing one eye tightly. However, it seems unlikely that paralysis of facial muscles caused the reduction in electrodermal response to the soapy eye drop in patients with a facial nerve lesion, because the reduction persisted for several minutes after the soap had been washed from the eye. Nevertheless, the present findings need to be confirmed using a more direct measure of sweating than electrodermal activity.
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did not increase the effects of sympathetic outflow on the vasculature or sweat glands of the forehead.
ACKNOWLEDGEMENTS I wish to thank Professor B. Stokes for arranging access to his patients, and Professor J. W. Lance and Dr P. J. Goadsby for their constructive suggestions on an early version of this manuscript. This project was supported by grants from the Australian Brain Foundation, the Australian Research Council and Murdoch University. REFERENCES BICKFORD RG (1938) The mechanism of local sweating in response to faradism. Clinical Science, 3, 337-341. BOYER FC, GARDNER WJ (1949) Paroxysmal lacrimation (syndrome of crocodile tears) and its surgical treatment: relation to auriculotemporal syndrome. Archives of Neurology and Psychiatry, Chicago, 61, 5 6 - 6 4 . CHAHL LA (1988) Antidromic vasodHalation and neurogenic inflammation. Pharmacology and Therapeutics, 37, 275-300. CHOROBSKI J (1951) The syndrome of crocodile tears. Archives of Neurology and Psychiatry, Chicago, 65, 299-318. DRUMMOND PD, ANTHONY M (1985) Extracranial vascular responses to sublingual nitroglycerin and oxygen inhalation in cluster headache patients. Headache, 25, 70—74. DRUMMOND PD, FrNCH PM (1989) Reflex control of facial flushing during body heating in man. Brain, 112, 1351-1358. DRUMMOND PD, LANCE JW (1984) Thermographic changes in cluster headache. Neurology, Cleveland, 34, 1292-1298.
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Clinical significance of the findings Painful stimulation of the eye provoked a vascular response in the forehead similar to that observed in some patients during attacks of cluster headache (e.g. fig. 2B, Drummond and Lance, 1984; Drummond and Anthony, 1985). Discharge of the trigeminal nerve during attacks of cluster headache could increase facial blood flow, either by antidromic release of vasoactive agents, or by a trigeminal-parasympathetic reflex. The electrodermal response to ocular irritation is greatly exaggerated in patients with a postganglionic cervical sympathetic lesion, including patients with cluster headache (Drummond and Lance, 1992). Pathological lacrimal sweating could develop after cross-innervation of sweat glands by parasympathetic fibres (van Weerden et al., 1979). This mechanism could mediate paradoxical sweating in sympathetically denervated areas of the face during attacks of cluster headache (Sjaastad et al., 1981). The functional importance of the trigeminal-parasympathetic vasodilator reflex in the skin is uncertain. In intracranial vessels, the reflex could protect the blood supply to the brain during inflammatory states, or may play a role in thermoregulation (Walters et al., 1986). When the eye is irritated, blood flow to the lacrimal gland would need to increase to maintain tear flow. The vascular response might spill over to surrounding skin because the lacrimal gland and lower part of the forehead are both supplied by branches of the ophthalmic artery (Williams et al., 1989). The cutaneous response could also help to remove sources of irritation and begin repair.
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DRUMMOND PD, LANCE JW (1987) Facial flushing and sweating mediated by the sympathetic nervous system. Brain, 110, 7 9 3 - 8 0 3 . DRUMMOND PD, LANCE JW (1992) Pathological sweating and flushing accompanying the trigeminal lacrimal reflex in patients with cluster headache and in patients with a confirmed site of cervical sympathetic deficit: evidence for parasympathetic cross-innervation. Brain, 115, 1429—1445. DRUMMOND PD, GONSKJ A, LANCE JW (1983) Facia] flushing after thermocoagulation of the Gasserian ganglion. Journal of Neurology, Neurosurgery, and Psychiatry, 46, 611—616. GARDNER WJ, MCCUBBIN JW (1956) Auriculotemporal syndrome: gustatory sweating due to misdirection of regenerated nerve fibers. Journal of the American Medical Association, 160, 212—211. GLAISTER DH, HEARNSHAW JR, HEFFRON PF, PECK AW, PATEY DH (1958) The mechanism of
LAMBERT GA, BOGDUK N, GOADSBY PJ, DUCKWORTH JW, LANCE JW (1984) Decreased carotid arterial
resistance in cats in response to trigeminal stimulation. Journal of Neurosurgery, 61, 307 — 315. LANCE JW, LAMBERT GA, GOADSBY PJ, DUCKWORTH JW (1983) Brainstem influences on the cephalic
circulation: experimental data from cat and monkey of relevance to the mechanism of migraine. Headache, 23, 258-265. LIST CF, PEET MM (1938) Sweat secretion in man: IV. Sweat secretion of the face and its disturbances. Archives of Neurology and Psychiatry, Chicago, 40, 443-470. LUNDBLAD L, ANGGARD A, LUNDBERG JM (1983) Effects of antidromic trigeminal nerve stimulation in relation to parasympathetic vasodilation in cat nasal mucosa. Ada Physiologica Scandinavica, 119, 7-13. LYKKEN DT, VENABLES PH (1971) Direct measurement of skin conductance: a proposal for standardization. Psychophysiology, 8, 656—672. MANDAHL A, BILL A (1981) Ocular responses to antidromic trigeminal stimulation, intracameral prostaglandin E, and E?, capsaicin and substance P. Acta Physiologica Scandinavica, 112, 331 —338. MONRO PAG (1959) Sweating in the central mask of the face. In: Sympathectomy: An Anatomical and Physiological Study with Clinical Applications. By P. A. G. Monro. London: Oxford University Press, pp. 157-186. NORDIN M (1990) Sympathetic discharges in the human supraorbital nerve and their relation to sudo- and vasomotor responses. Journal of Physiology, London, 423, 241-255. SALVESEN R, SAND T, SJAASTAD O (1988) Cluster headache: combined assessment with pupillometry and evaporimetry. Cephalalgia, 8, 211-218. SALVESEN R, DE SOUZA CD, SJAASTAD O (1989) Homer's syndrome. Sweat gland and pupillary responsiveness in two cases with a probable 3rd neurone dysfunction. Cephalalgia, 9, 63—70. SJAASTAD O, SAUNTE C, RUSSELL D, HESTNES A, MARVIK R (1981) Cluster headache. The sweating
pattern during spontaneous attacks. Cephalalgia, 1, 233-244. STEVENS LM, LANDIS SC (1987) Development and properties of the secretory response in rat sweat glands: relationship to the induction of cholinergic function in sweat gland innervation. Developmental Biology, 123, 179-190. WALSH FB, HOYT WF (1969) The neurology of lacrimal section. In: Clinical Neuro-ophthalmology, Volume 1. Third edition. By F. B. Walsh and W. F. Hoyt. Baltimore: Williams and Wilkins, pp. 551 - 5 5 5 . WALTERS BB, GILLESPIE SA, MosKowrrz MA (1986) Cerebrovascular projections from the sphenopalatine and otic ganglia to the middle cerebral artery of the cat. Stroke, 17, 488—494.
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post-parotidectomy gustatory sweating (the auriculotemporal syndrome). British Medical Journal, ii, 942-946. GOADSBY PJ, MACDONALD GJ (1985) Extracranial vasodilation mediated by vasoactive intestinal polypeptide (VIP). Brain Research, Amsterdam, 329, 285-288. GOADSBY PJ, EDVINSSON L, EKMAN R (1988) Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Annals of Neurology, 23, 193-1%. GONZALEZ G, ONOFRIO BM, KERR FWL (1975) Vasodilator system for the face. Journal of Neurosurgery, 42, 6 % - 7 0 3 . HOLZER P (1988) Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience, 24, 739 — 768. JANOWITZ HD, GROSSMAN MJ (1950) The response of the sweat glands to some locally acting agents in human subjects. Journal of Investigative Dermatology, 14, 453—458.
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WEERDEN TW VAN, HOUTMAN WA, SCHWEITZER NMJ, MINDERHOUD JM (1979) Lacrimal sweating in
a patient with Raeder's syndrome. Clinical Neurology and Neurosurgcry, 81, 119—121. WILKINS RW, NEWMAN HW, DOUPE J (1938) The local sweat response to faradic stimulation. Brain, 61, 290-297. WILUAMS PL, WARWICK R, DYSON M, BANNISTER LH (1989) Cray's Anatomy. Thirty-seventh edition.
Edinburgh: Churchill Livingstone. {Received December 17, 1991. Revised March 20, 1992. Accepted April 30, 1992)
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