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Salivary changes associated with experimental motion sickness condition in man
Journal of the Autonomic Nervous System, 22 (1988) 91-96 Elsevier
91
JAN 00793
Research Papers
Salivary changes associated with experimental motion sickness condition in man Carlos R. G o r d o n
1, H a n n a
Ben-Aryeh 2, R a y m o n d e Szargel and D o v Laufer 2
2, Joseph
Attias
1, Arnon
Rolnick 1
1 Motion Sickness and Human Performance Laboratory, Israel Naval Hyperbaric Institute and 2 Laboratory of Oral Biology, Department of Oral Surgery, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa (Israel) (Received 9 October 1987) (Revised version received 17 December 1987) (Accepted 18 December 1987)
Key words: Motion sickness; Salivary flow; Salivary composition; Vestibular stimulation; Rotation Abstract The effect of experimental motion sickness condition (rotation) on salivary flow and composition was studied in 34 healthy male volunteers. In most subjects, the flow rate of whole saliva was significantly decreased, while the potassium concentration was markedly increased during rotation. These results contrast with the classic reports of subjectively increased salivation in the first stages of motion sickness and may tentatively be explained in terms of sympathetic activation. The salivary protein concentration and secretion rate observed before and during rotation were consistently higher in those subjects categorized as moderately or severely sick during rotation. The salivary protein levels may perhaps be considered as an additional objective variable in the prediction of susceptibility to motion sickness.
Introduction Motion sickness is a transient disturbance in subjects with an intact healthy labyrinth who are exposed to certain kinds of movements. The most frequent signs and symptoms in man include malaise, pallor, cold sweating, increased salivation, nausea and vomiting [16,19,23]. Increased salivation with swallowing frequently precedes or accompanies nausea. Subjective grading of salivation is included within a list of symptoms and signs used for diagnosis of acute motion sickness
Correspondence: H. Ben-Aryeh, Laboratory of Oral Biology, Department of Oral and Maxillofacial Surgery, Rambam Medical Center, P.O.B. 9602, Haifa 31096, Israel.
[10]. In animals such as dogs and cats, hypersalivation with copious drooling is also associated with experimental motion sickness [16,18,22]. Although the physiologic mechanisms of motion sickness are still not completely understood, some of its most frequent signs, such as pallor, sweating, salivation and vomiting, can be explained in terms of vestibular-autonomic reactions [14]. Autonomic nervous system functions during motion sickness have been investigated by measuring pallor, galvanic skin responses, cardiovascular changes and gastrointestinal motility [14]. Salivation has been evaluated in man only by subjective reports and in animals only by examiner observation. To the best of our knowledge, no systematic efforts were previously made to measure salivary secretion during motion sickness.
0165-1838/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)
92
The purpose of the present study was to measure possible changes in salivary flow rate and composition in subjects exposed to experimental motion sickness condition.
Materials and Methods
Thirty-four healthy males, 18-19 years of age, participated in the study. The study protocol was approved by the local Helsinki Committee, and all participants signed and informed-consent form. Subjects were completely drug-free at least 48 h before the study. All experimental procedures were clearly explained to the subjects before the study. Experimental motion sickness condition was produced and evaluated according to procedures described for the brief vestibular disorientation test (BVDT) [1,2]. This test is based on cross-coupled (Coriolis) vestibular reactions elicited by tilting the head 45 ° during whole-body rotation. The BVDT is commonly used in the assessment of susceptibility to motion sickness [19]. Each subject, with eyes closed and head upright, was seated in a rotary chair which was accelerated at 15 °/s2 to a constant velocity of 90 ° / s (15 rpm). After 30 s, the subject was asked to assume and to maintain for 30 s each of the following head positions: right tilt, upright, left tilt, upright, right tilt, upright, left tilt, upright, forward tilt and upright. After completion of this sequence (330 s), the chair was stopped by a 1 5 ° / s 2 deceleration, and the subject was asked to open his eyes after the illusory sensation of motion had ceased. Tilting the head during whole-body rotation induces a complex illusory experience of motion, sometimes accompanied by pallor, sweating, nausea and vomiting [11]. The BVDT score was obtained from 3 examiners estimating pallor, sweating, facial expression, unsteadiness, speed of recovery and overall performance on a 10-point scale. Sweating was rated by comparing pre- and post-rotation sweating levels by touching the subject's palms and forehead. Pallor was graded by observing changes in skin tone coloration. Facial expression was evaluated by a variety of facial changes reflecting emotional reactions to the rotatory experience. Unsteadiness was evaluated at the
end of the rotation. Slow recovery reflected the rate at which reactions to the rotation stimuli subsided after stopping. Overall performance was evaluated in terms of the subject's behavior during the test. An individual examiner's score was obtained by summing up his judgments on the 6 above factors. The BVDT score for a given subject was the mean of these individual ratings [2]. After rotation, each subject was asked to fill out a brief questionnaire rating his own symptoms during the experience. Whole saliva was collected by the spitting method [9,11]. This method is commonly used in clinical practice and research. High scores of reliability and accuracy have been reported and compare favorably with other techniques of salivary collection [17]. Salivary collections were performed in the following conditions: (1) in the control condition, approximately 30 min before rotation each subject was seated with eyes closed and asked to spit into a test tube for 5 min while performing the same head movements as those of the BVDT. (2) In the rotation condition, saliva collection was performed in the same manner while the subject was exposed to experimental motion sickness condition (rotation). Salivary collections were performed at least 1 h after meals. In case of severe nausea or retching during rotation or if the subject requested, the chair was stopped and the rest of the saliva collection was completed (4 subjects). Salivary volume was mehsured in 5-ml cylinders with a 0.1-ml scale, and flow rate was calculated with accuracy of within 2%. Sodium and potassium concentrations were measured by flame photometry, and protein concentrations by the Lowry method [15]. Student's t-test and Pearson's correlation coefficients were used for statistical analysis. P < 0.05 was considered significant.
Results
Table I summarizes the mean salivary composition and flow rate in control and rotation conditions. The salivary flow rate was significantly reduced ( P < 0.001) during rotation as compared with the
93 TABLE I
Salivary composition and flow rate in control and rotation conditions (n = 34) Values shown are means 5: S.D.
Control Rotation
Flow rate (ml/min)
Na (mEq/l)
K (mEq/l)
Total protein (mg%)
Na (l~Eq/min) ~"
K (ItEq/min) ¢
Total protein (rag~rain) t
0.36 -I-0.29 0.23 5:0.23 * *
4.7 + 2.5 6.6 5:6.2
21.9 + 7.1 25.4 5:11.3 *
198.0 -t- 125.5 200.4 5:82.6
1.8 + 2.3 1.5 5:1.7
7.3 + 5.3 5.9 + 4.2 * *
67.5 + 49.6 44.9 + 22.9 * *
* P<0.01; ** P < 0.001 (paired t-test). t The rate of secretion of every variable for each subject was calculated as concentration x flow rate.
control condition. It was decreased in 27 of the 34 subjects (79%) in response to rotation; in 5 subjects salivary flow increased, and in the remaining 2 subjects no changes were measured (Fig. 1). Sodium concentration was higher during rotation than in the control condition, but the difference was not statistically significant. Potassium concentration was markedly elevated during rotation ( P < 0.01). Protein concentrations were similar in the control and rotation conditions. Sodium,
*100t • T
.40
[]
i C
~
o_ -20.
"~
-40.
U 0
~
-80 _
-80
t •
- ~oo
Fig. 1. Percentage difference (/t%) between salivary flow rates b e f o r e and during rotation. I, Moderately and severely sick subjects; D, slightly and mildly sick subjects. Dotted areas indicate mean + S.D. A%, percentage difference [(qD/control flow rate)×lO0]; qD = quantity of difference (control flow rate-rotation flow rate).
potassium and total-protein secretion rates were reduced during rotation. Significant differences were found for potassium and protein secretion rates. Examination of the B V D T scores and the selfreporting questionnaires revealed that all the subjects suffered from at least slight motion sickness symptomatology during rotation. Based on the B V D T scores obtained from the examiners and on the questionnaires filled out by the subjects, motion sickness is categorized as slight, mild, moderate or severe [10,20]. According to this categorization, the subjects were divided into two subgroups: subgroup A included 22 subjects with slight or mild symptomatology during rotation; subgroup B included 12 subjects with moderate or severe symptbmatology during rotation. Table II summarizes the mean salivary composition and flow rate for the two subgroups in the control and rotation conditions. There were no significant differences in salivary flow rate and electrolyte concentration and secretion rate between the two subgroups. In contrast, protein concentration and secretion rate were elevated in moderately and severely sick subjects in both the control and rotation conditions. The differences between the subgroups reached statistical significance ( P < 0.05) for protein concentration during rotation and for protein secretion rate during the control condition. Fig. 1 shows the percentage differences in salivary flow for each subject. Pearson's correlation coefficients were calculated between all the salivary variables, the examiner scores and the self-rating scores. A signifi-
94 TABLE II
Saliva~ composition and flow rate in the different subgroups and conditions Values shown are means ± S.D.
Flow rate (ml/min)
Na (mEq/l)
K (mEq/l)
Total protein (rag%)
Na (gEq/min) ~
K (gEq/min) t
Total protein (mg/min) +
0.37 + 0.35 0.34 ± 0.17
4.6 + 2.5 4.9 ± 2.7
21.8 + 7.9 22.2 ± 5.4
157.9 + 66.4 249.2 ± 164.1
1.9 ± 2.8 1.7 ± 8.2
7.5 ± 6.1 6.9 ± 3.7
49.6 ± 25.2 90.2 ± 63.8 *
0.23+0.16 0.23 ± 0.10
6.3±7.1 7.1 + 4.5
25.6+12.4 24.9 ± 9.6
168.1± 54.2 238.5 ± 96.0 *
1.5±2.1 1.5 ± 0.9
6.3±4.9 5.1 + 2.4
36.7±16.1 54.7 _+ 26.6
Control A (n = 22) B (n = 12) Rotation A ( n = 22) B (n = 12)
A, slightly and mildly sick subjects during rotation; B, moderately and severely sick subjects during rotation. * P < 0.5 (unpaired t-test between group A and group B subjects), t The rate of secretion of every variable for each subject was calculated as concentration × flow.
cant positive correlation was found between examiner scores and subject motion sickness ratings (r = 0.84, df = 33, P < 0.001). No significant correlations were found between salivary flow rate and the examiner or subject scores. A significant positive correlation was found between control protein concentration and the examiner score (r = 0.40, df = 23, P < 0.05). A positive correlation, bordering on statistical significance, was found between protein concentration during rotation and the examiner motion sickness score (r = 0.39, df = 22, P < 0.1). These correlations suggest that the higher the salivary protein concentration, the greater the motion sickness severity. A significant positive correlation was found between control salivary flow and qD ( r = 0 . 7 2 , d f = 33, P < 0.001), i.e. the higher the control salivary flow rate, the greater the quantity of decrease in flow rate in response to rotation.
Discussion
The present results demonstrate a significant decrease of whole-salivary flow rate in response to acute experimental motion sickness conditions (i.e., rotation) in man. The salivary flow rate was lowered in 79% of our subjects exposed to brief vestibular stimulation. To the best of our knowledge, this is the first study reporting objective measurements of salivary secretion during acute motion-sickness conditions. Salivary secretion was
measured in crew members of the Skylab mission, but the possible presence of motion sickness was not mentioned in that study [4]. The objective reduction of salivary flow rate in our subjects contrasts with the classic reports of increased salivation with swallowing in the first stages of motion sickness in man [15,20,23]. It should be remembered that in all these studies the reported changes in sahvation were subjectively estimated. This discrepancy may be explained in at least two ways: (1) a possible transient impairment of swallowing during motion-sickness condition may produce an accumulation of saliva in the oral cavity, with a subjective feeling of increased salivation. A similar insufficient mechanism for removal of saliva has been described in a variety of clinical disorders such as cerebral, bulbar and pseudobulbar palsies [6,8,13]. (2) Feelings of increased salivation and nausea may be related to each other on the basis of anatomical proximity of 'nauseogenic and emetic centers' (area postrema) and of swallowing and salivary areas in the brainstem [5]. All the subjects suffered from at least slight motion sickness symptoms during rotation. While salivary flow rate was consistently reduced in our subjects during rotation, we failed to find a correlation between the extent of salivary flow decrease and motion sickness severity. That is, during acute vestibular stimulation, the salivary flow decreased i n d e p e n d e n t l y of m o t i o n sickness severity evaluated by both the subjects' and the examiners'
95
scores. In agreement with previous reports using antisialogogue drugs [9,17], there was a positive correlation between initial (control) flow rate and quantity of decrease; i.e. high saliva producers responded to vestibular stimulation with a significantly greater decrease in salivary flow. The elevation of sodium concentration during rotation--although statistically non-signific a n t - i s of interest. Salivary sodium concentration is directly flow-dependent [3,20]. We cannot provide a satisfactory explanation for the increased salivary sodium concentration in our subjects concomitant with the marked decrease in salivary flow rate during rotation. Salivary potassium concentration was significantly elevated during rotation. Potassium concentration can be slightly elevated as a result of salivary flow decrease. In addition, sympathetic stimulation causes higher salivary potassium concentration than does parasympathetic stimulation
of clinical presentation: one in which parasympathetic symptomatology was predominant ('vagotonic subjects') and another characterized by signs of sympathetic activation ('sympathotonic subjects') [23]. The diminution of salivary flow rate and, at least partially, the increased potassium concentration found in our subjects during rotation can be explained in terms of sympathetic activation [3]. Further studies measuring differential salivary gland secretions will contribute to clarification of the possible sympathetically or parasympathetically mediated salivary changes during different motion sickness conditions.
Acknowledgement The authors thank Miss Ruth Singer for excellent secretarial help.
[31. Total protein concentration was unchanged during rotation as compared with the control condition. It is of interest that salivary protein concentration and secretion rate in both the control and rotation conditions were consistently higher in those subjects categorized as moderately or severely sick during rotation (Table II). Many research efforts have been made to predict motion sickness susceptibility in naval, air and space-crew personnel [16,20]. Thus, our observation of elevated protein is noteworthy. Further studies should be conducted to confirm the possibility of using salivary protein levels as an additional objective variable in the prediction of motion sickness susceptibility. Although in the present study we did not investigate the physiologic mechanisms regulating vestibular-autonomic responses, some comments are appropriate. The rapid changes in salivary flow rate detected in our subjects in response to vestibular stimulation point to a neurally or hormonally mediated mechanism. The clinical picture of motion sickness--cold perspiration, sialorrhea, slow pulse, low temperature, nausea and vomiting--is considered by some investigators to be a result of parasympathetic activation [7]. Moreover, earlier studies differentiated two forms
References 1 Ambler, R.K. and Guedry, F.E., Reliability and validity of the brief vestibular disorientation test compared under 10 rpm and 15 rpm, Aerospace Med., 42 (1971) 186-189. 2 Ambler, R.K. and Guedry, F.E., A Manual for the Brief Vestibular Disorientation Test, NAMRL Report No. 78-3, Naval Aerospace Medical Research Laboratory, Pensacola, FL, 1978. 3 Brobeck, J.R., Best and Taylor's Physiological Basis of Medical Practice, 10th edn., Williams&Wilkins, Baltimore, MD, 1981. 4 Brown, L.R., Frome, W.J., Wheatcroft, M.G., Riggan, L.J., BusseU, N.E. and Johnston, D.A., The effect of Skylab on the chemical composition of saliva, J. Dent. Res., 56 (1977) 1137-1143. 5 Carpenter, M.B., Core Text of Neuroanatomy, 2nd edn., Williams&Wilkins, Baltimore/London, 1984. 6 De Jong, R.N., Neurologic Examination, 4th edn., Harper&Row, Hagerstown, MD, 1979. 7 De Witt, G., Seasickness (motion sickness), Acta Otolaryngol., Suppl. 108 (1953). 8 Ekedahl, C., Mansson, I. and Sandberg, N., Swallowing dysfunction in the brain-damaged with drooling, Acta OtolaryngoL, 78 (1974) 141-149. 9 Gordon, C., Ben-Aryeh, H., Attias, J., Szargel, R. and Gutman, D , Effect of transdermal scopolamine on salivation, J. Clin. Pharmacol., 25 (1985) 407-412. 10 Graybiei, A., Wood, C.D., Miller, E.F. and Cramer, D.B. Diagnostic criteria for grading the severity of acute motion sickness, Aerospace Med., 39 (1968) 453-455. 11 Guedry, F.E., Psychophysics of vestibular sensation. In
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12
13
14
15
16 17
H.H. Kornhuber (Ed.), Handbook of Sensory Physiology, Vol. VI/2, Vestibular System, Springer, Berlin, 1974, pp. 3-154. Gutman, D. and Ben-Aryeh, H., The influence of age on salivary content and rate flow, Int. J. Oral Surg., 3 (1974) 314-317. Harris, M.M. and Dignam, P.F., A non-surgical method of reducing drooling in cerebral-palsied children, Dev. Meal Child Neurol., 22 (1980) 293-299. Johnson, W.H. and Jonkees, L.B.W., Motion sickness. Part 1: Aetiology and autonomic effects. In H.H. Kornhuber (Ed.), Handbook of Sensory Physiology, Vol. VI/2, Vestibular System, Springer, Berlin, York, 1974, pp. 389-404. Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J., Protein determination with the Folin phenol reagent, J. Biol. Chem., 193 (1951) 265-275. Money, K.E., Motion sickness, Physiol. Rev., 50 (1970) 1-39. Navazesh, M. and Christensen, C.M., A comparison of
18
19 20
21 22
23
whole-mouth resting and stimulated salivary measurement procedures, J. Dent. Res., 61 (1982) 1158-1162. Noble, R.L., Observations on various types of motion causing vomiting in animals, Can. J. Res. Sect. E, 23 (1945) 212-225. Reason, J.T. and Brand, J.J., Motion Sickness, Academic Press, London, 1975. Reason, J.T. and Diaz, E., Simulator sickness in passive observers, Flying Personnel Research Committee, Report no. 1310, 1971. Schneyer, L.H., Young, J.A. and Schneyer, C.A., Salivary secretion of electrolytes, Physiol. Reo., 52 (1972) 720-769. Suri, K.B., Crampton, G.H. and Dawnton, N.G. Motion sickness in cats. A symptom-rating scale used in laboratory and flight tests, Aoiat. Space Environ. Med., 50 (1979) 614-618. Tyler, D.B. and Bard, P., Motion sickness, Physiol. Rev., 29 (1949) 311-369.
91
JAN 00793
Research Papers
Salivary changes associated with experimental motion sickness condition in man Carlos R. G o r d o n
1, H a n n a
Ben-Aryeh 2, R a y m o n d e Szargel and D o v Laufer 2
2, Joseph
Attias
1, Arnon
Rolnick 1
1 Motion Sickness and Human Performance Laboratory, Israel Naval Hyperbaric Institute and 2 Laboratory of Oral Biology, Department of Oral Surgery, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa (Israel) (Received 9 October 1987) (Revised version received 17 December 1987) (Accepted 18 December 1987)
Key words: Motion sickness; Salivary flow; Salivary composition; Vestibular stimulation; Rotation Abstract The effect of experimental motion sickness condition (rotation) on salivary flow and composition was studied in 34 healthy male volunteers. In most subjects, the flow rate of whole saliva was significantly decreased, while the potassium concentration was markedly increased during rotation. These results contrast with the classic reports of subjectively increased salivation in the first stages of motion sickness and may tentatively be explained in terms of sympathetic activation. The salivary protein concentration and secretion rate observed before and during rotation were consistently higher in those subjects categorized as moderately or severely sick during rotation. The salivary protein levels may perhaps be considered as an additional objective variable in the prediction of susceptibility to motion sickness.
Introduction Motion sickness is a transient disturbance in subjects with an intact healthy labyrinth who are exposed to certain kinds of movements. The most frequent signs and symptoms in man include malaise, pallor, cold sweating, increased salivation, nausea and vomiting [16,19,23]. Increased salivation with swallowing frequently precedes or accompanies nausea. Subjective grading of salivation is included within a list of symptoms and signs used for diagnosis of acute motion sickness
Correspondence: H. Ben-Aryeh, Laboratory of Oral Biology, Department of Oral and Maxillofacial Surgery, Rambam Medical Center, P.O.B. 9602, Haifa 31096, Israel.
[10]. In animals such as dogs and cats, hypersalivation with copious drooling is also associated with experimental motion sickness [16,18,22]. Although the physiologic mechanisms of motion sickness are still not completely understood, some of its most frequent signs, such as pallor, sweating, salivation and vomiting, can be explained in terms of vestibular-autonomic reactions [14]. Autonomic nervous system functions during motion sickness have been investigated by measuring pallor, galvanic skin responses, cardiovascular changes and gastrointestinal motility [14]. Salivation has been evaluated in man only by subjective reports and in animals only by examiner observation. To the best of our knowledge, no systematic efforts were previously made to measure salivary secretion during motion sickness.
0165-1838/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)
92
The purpose of the present study was to measure possible changes in salivary flow rate and composition in subjects exposed to experimental motion sickness condition.
Materials and Methods
Thirty-four healthy males, 18-19 years of age, participated in the study. The study protocol was approved by the local Helsinki Committee, and all participants signed and informed-consent form. Subjects were completely drug-free at least 48 h before the study. All experimental procedures were clearly explained to the subjects before the study. Experimental motion sickness condition was produced and evaluated according to procedures described for the brief vestibular disorientation test (BVDT) [1,2]. This test is based on cross-coupled (Coriolis) vestibular reactions elicited by tilting the head 45 ° during whole-body rotation. The BVDT is commonly used in the assessment of susceptibility to motion sickness [19]. Each subject, with eyes closed and head upright, was seated in a rotary chair which was accelerated at 15 °/s2 to a constant velocity of 90 ° / s (15 rpm). After 30 s, the subject was asked to assume and to maintain for 30 s each of the following head positions: right tilt, upright, left tilt, upright, right tilt, upright, left tilt, upright, forward tilt and upright. After completion of this sequence (330 s), the chair was stopped by a 1 5 ° / s 2 deceleration, and the subject was asked to open his eyes after the illusory sensation of motion had ceased. Tilting the head during whole-body rotation induces a complex illusory experience of motion, sometimes accompanied by pallor, sweating, nausea and vomiting [11]. The BVDT score was obtained from 3 examiners estimating pallor, sweating, facial expression, unsteadiness, speed of recovery and overall performance on a 10-point scale. Sweating was rated by comparing pre- and post-rotation sweating levels by touching the subject's palms and forehead. Pallor was graded by observing changes in skin tone coloration. Facial expression was evaluated by a variety of facial changes reflecting emotional reactions to the rotatory experience. Unsteadiness was evaluated at the
end of the rotation. Slow recovery reflected the rate at which reactions to the rotation stimuli subsided after stopping. Overall performance was evaluated in terms of the subject's behavior during the test. An individual examiner's score was obtained by summing up his judgments on the 6 above factors. The BVDT score for a given subject was the mean of these individual ratings [2]. After rotation, each subject was asked to fill out a brief questionnaire rating his own symptoms during the experience. Whole saliva was collected by the spitting method [9,11]. This method is commonly used in clinical practice and research. High scores of reliability and accuracy have been reported and compare favorably with other techniques of salivary collection [17]. Salivary collections were performed in the following conditions: (1) in the control condition, approximately 30 min before rotation each subject was seated with eyes closed and asked to spit into a test tube for 5 min while performing the same head movements as those of the BVDT. (2) In the rotation condition, saliva collection was performed in the same manner while the subject was exposed to experimental motion sickness condition (rotation). Salivary collections were performed at least 1 h after meals. In case of severe nausea or retching during rotation or if the subject requested, the chair was stopped and the rest of the saliva collection was completed (4 subjects). Salivary volume was mehsured in 5-ml cylinders with a 0.1-ml scale, and flow rate was calculated with accuracy of within 2%. Sodium and potassium concentrations were measured by flame photometry, and protein concentrations by the Lowry method [15]. Student's t-test and Pearson's correlation coefficients were used for statistical analysis. P < 0.05 was considered significant.
Results
Table I summarizes the mean salivary composition and flow rate in control and rotation conditions. The salivary flow rate was significantly reduced ( P < 0.001) during rotation as compared with the
93 TABLE I
Salivary composition and flow rate in control and rotation conditions (n = 34) Values shown are means 5: S.D.
Control Rotation
Flow rate (ml/min)
Na (mEq/l)
K (mEq/l)
Total protein (mg%)
Na (l~Eq/min) ~"
K (ItEq/min) ¢
Total protein (rag~rain) t
0.36 -I-0.29 0.23 5:0.23 * *
4.7 + 2.5 6.6 5:6.2
21.9 + 7.1 25.4 5:11.3 *
198.0 -t- 125.5 200.4 5:82.6
1.8 + 2.3 1.5 5:1.7
7.3 + 5.3 5.9 + 4.2 * *
67.5 + 49.6 44.9 + 22.9 * *
* P<0.01; ** P < 0.001 (paired t-test). t The rate of secretion of every variable for each subject was calculated as concentration x flow rate.
control condition. It was decreased in 27 of the 34 subjects (79%) in response to rotation; in 5 subjects salivary flow increased, and in the remaining 2 subjects no changes were measured (Fig. 1). Sodium concentration was higher during rotation than in the control condition, but the difference was not statistically significant. Potassium concentration was markedly elevated during rotation ( P < 0.01). Protein concentrations were similar in the control and rotation conditions. Sodium,
*100t • T
.40
[]
i C
~
o_ -20.
"~
-40.
U 0
~
-80 _
-80
t •
- ~oo
Fig. 1. Percentage difference (/t%) between salivary flow rates b e f o r e and during rotation. I, Moderately and severely sick subjects; D, slightly and mildly sick subjects. Dotted areas indicate mean + S.D. A%, percentage difference [(qD/control flow rate)×lO0]; qD = quantity of difference (control flow rate-rotation flow rate).
potassium and total-protein secretion rates were reduced during rotation. Significant differences were found for potassium and protein secretion rates. Examination of the B V D T scores and the selfreporting questionnaires revealed that all the subjects suffered from at least slight motion sickness symptomatology during rotation. Based on the B V D T scores obtained from the examiners and on the questionnaires filled out by the subjects, motion sickness is categorized as slight, mild, moderate or severe [10,20]. According to this categorization, the subjects were divided into two subgroups: subgroup A included 22 subjects with slight or mild symptomatology during rotation; subgroup B included 12 subjects with moderate or severe symptbmatology during rotation. Table II summarizes the mean salivary composition and flow rate for the two subgroups in the control and rotation conditions. There were no significant differences in salivary flow rate and electrolyte concentration and secretion rate between the two subgroups. In contrast, protein concentration and secretion rate were elevated in moderately and severely sick subjects in both the control and rotation conditions. The differences between the subgroups reached statistical significance ( P < 0.05) for protein concentration during rotation and for protein secretion rate during the control condition. Fig. 1 shows the percentage differences in salivary flow for each subject. Pearson's correlation coefficients were calculated between all the salivary variables, the examiner scores and the self-rating scores. A signifi-
94 TABLE II
Saliva~ composition and flow rate in the different subgroups and conditions Values shown are means ± S.D.
Flow rate (ml/min)
Na (mEq/l)
K (mEq/l)
Total protein (rag%)
Na (gEq/min) ~
K (gEq/min) t
Total protein (mg/min) +
0.37 + 0.35 0.34 ± 0.17
4.6 + 2.5 4.9 ± 2.7
21.8 + 7.9 22.2 ± 5.4
157.9 + 66.4 249.2 ± 164.1
1.9 ± 2.8 1.7 ± 8.2
7.5 ± 6.1 6.9 ± 3.7
49.6 ± 25.2 90.2 ± 63.8 *
0.23+0.16 0.23 ± 0.10
6.3±7.1 7.1 + 4.5
25.6+12.4 24.9 ± 9.6
168.1± 54.2 238.5 ± 96.0 *
1.5±2.1 1.5 ± 0.9
6.3±4.9 5.1 + 2.4
36.7±16.1 54.7 _+ 26.6
Control A (n = 22) B (n = 12) Rotation A ( n = 22) B (n = 12)
A, slightly and mildly sick subjects during rotation; B, moderately and severely sick subjects during rotation. * P < 0.5 (unpaired t-test between group A and group B subjects), t The rate of secretion of every variable for each subject was calculated as concentration × flow.
cant positive correlation was found between examiner scores and subject motion sickness ratings (r = 0.84, df = 33, P < 0.001). No significant correlations were found between salivary flow rate and the examiner or subject scores. A significant positive correlation was found between control protein concentration and the examiner score (r = 0.40, df = 23, P < 0.05). A positive correlation, bordering on statistical significance, was found between protein concentration during rotation and the examiner motion sickness score (r = 0.39, df = 22, P < 0.1). These correlations suggest that the higher the salivary protein concentration, the greater the motion sickness severity. A significant positive correlation was found between control salivary flow and qD ( r = 0 . 7 2 , d f = 33, P < 0.001), i.e. the higher the control salivary flow rate, the greater the quantity of decrease in flow rate in response to rotation.
Discussion
The present results demonstrate a significant decrease of whole-salivary flow rate in response to acute experimental motion sickness conditions (i.e., rotation) in man. The salivary flow rate was lowered in 79% of our subjects exposed to brief vestibular stimulation. To the best of our knowledge, this is the first study reporting objective measurements of salivary secretion during acute motion-sickness conditions. Salivary secretion was
measured in crew members of the Skylab mission, but the possible presence of motion sickness was not mentioned in that study [4]. The objective reduction of salivary flow rate in our subjects contrasts with the classic reports of increased salivation with swallowing in the first stages of motion sickness in man [15,20,23]. It should be remembered that in all these studies the reported changes in sahvation were subjectively estimated. This discrepancy may be explained in at least two ways: (1) a possible transient impairment of swallowing during motion-sickness condition may produce an accumulation of saliva in the oral cavity, with a subjective feeling of increased salivation. A similar insufficient mechanism for removal of saliva has been described in a variety of clinical disorders such as cerebral, bulbar and pseudobulbar palsies [6,8,13]. (2) Feelings of increased salivation and nausea may be related to each other on the basis of anatomical proximity of 'nauseogenic and emetic centers' (area postrema) and of swallowing and salivary areas in the brainstem [5]. All the subjects suffered from at least slight motion sickness symptoms during rotation. While salivary flow rate was consistently reduced in our subjects during rotation, we failed to find a correlation between the extent of salivary flow decrease and motion sickness severity. That is, during acute vestibular stimulation, the salivary flow decreased i n d e p e n d e n t l y of m o t i o n sickness severity evaluated by both the subjects' and the examiners'
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scores. In agreement with previous reports using antisialogogue drugs [9,17], there was a positive correlation between initial (control) flow rate and quantity of decrease; i.e. high saliva producers responded to vestibular stimulation with a significantly greater decrease in salivary flow. The elevation of sodium concentration during rotation--although statistically non-signific a n t - i s of interest. Salivary sodium concentration is directly flow-dependent [3,20]. We cannot provide a satisfactory explanation for the increased salivary sodium concentration in our subjects concomitant with the marked decrease in salivary flow rate during rotation. Salivary potassium concentration was significantly elevated during rotation. Potassium concentration can be slightly elevated as a result of salivary flow decrease. In addition, sympathetic stimulation causes higher salivary potassium concentration than does parasympathetic stimulation
of clinical presentation: one in which parasympathetic symptomatology was predominant ('vagotonic subjects') and another characterized by signs of sympathetic activation ('sympathotonic subjects') [23]. The diminution of salivary flow rate and, at least partially, the increased potassium concentration found in our subjects during rotation can be explained in terms of sympathetic activation [3]. Further studies measuring differential salivary gland secretions will contribute to clarification of the possible sympathetically or parasympathetically mediated salivary changes during different motion sickness conditions.
Acknowledgement The authors thank Miss Ruth Singer for excellent secretarial help.
[31. Total protein concentration was unchanged during rotation as compared with the control condition. It is of interest that salivary protein concentration and secretion rate in both the control and rotation conditions were consistently higher in those subjects categorized as moderately or severely sick during rotation (Table II). Many research efforts have been made to predict motion sickness susceptibility in naval, air and space-crew personnel [16,20]. Thus, our observation of elevated protein is noteworthy. Further studies should be conducted to confirm the possibility of using salivary protein levels as an additional objective variable in the prediction of motion sickness susceptibility. Although in the present study we did not investigate the physiologic mechanisms regulating vestibular-autonomic responses, some comments are appropriate. The rapid changes in salivary flow rate detected in our subjects in response to vestibular stimulation point to a neurally or hormonally mediated mechanism. The clinical picture of motion sickness--cold perspiration, sialorrhea, slow pulse, low temperature, nausea and vomiting--is considered by some investigators to be a result of parasympathetic activation [7]. Moreover, earlier studies differentiated two forms
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