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Upper airway motor outputs during sneezing and coughing in decerebrate cats
Neuroscience Research 32 (1998) 131 – 135
Upper airway motor outputs during sneezing and coughing in decerebrate cats Isamu Satoh a,*, Keisuke Shiba a, Nobuhiro Kobayashi a, Yoshio Nakajima b, Akiyoshi Konno a a
Department of Otolaryngology, School of Medicine, Chiba Uni6ersity, 1 -8 -1 Inohana, Chiba 260 -8670, Japan b Department of Physiology, School of Medicine, Chiba Uni6ersity, 1 -8 -1 Inohana, Chiba 260 -8670, Japan Received 19 February 1998; accepted 21 July 1998
Abstract The purposes of the present study were to determine which upper airway movements cause a difference in the expiratory airflow pathway between sneezing and coughing, and to develop a new animal model for studying the neural mechanism of sneezing in paralyzed animals, i.e. fictive sneezing. We compared the upper airway motor patterns of sneezing and coughing, induced by electrical stimulation of the anterior ethmoidal nerve (AEN) and superior laryngeal nerve, respectively, in non-paralyzed decerebrate cats. Respiratory and laryngeal motor patterns that consisted of an inspiration phase, compression phase, and expulsion phase were observed for both sneezing and coughing. The main difference was observed in the activity of the elevator of the back of the tongue, styloglossus (SG) muscle, which was explosively activated during the expulsion phase of sneezing, whereas it was virtually silent during coughing. The nasopharyngeal closers were weakly to moderately activated during sneezing. Their activities during coughing were weaker than during sneezing. Furthermore, the AEN-induced activities of the phrenic and abdominal nerves and the lateral branch of the hypoglossal nerve (lat-XII), which innervates the SG muscle, in paralyzed cats were consistent with the activities of the diaphragm, abdominal, and SG muscles during actual sneezing in non-paralyzed cats. Thus, we conclude that tongue movement is the main difference in the motor outputs between sneezing and coughing, which probably causes greater nasal airflow in sneezing, and that it is necessary to record the activity of the lat-XII to identify fictive sneezing in paralyzed cats. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Sneeze; Cough; Upper airway reflex; Styloglossus muscle; Hypoglossal nerve; Fictive sneezing; Cat
1. Introduction Sneezing and coughing, induced by stimulation of the nasal and laryngeal mucosae respectively, are defensive reflexes of the airways. Both reflexes consist of an inspiration phase, compression phase, in which powerful expiratory effort with vocal fold adduction abruptly increases the subglottic pressure, and expulsion phase, in which continuous expiratory effort with vocal fold abduction causes explosive airflow (Korpas and Tomori, 1979). The main difference between sneezing and * Corresponding author. Tel.: + 81-43-2227171, ext. 5102; Fax: +81-43-2262028; e-mail: [email protected].
coughing is that the expiratory nasal airflow in sneezing is much greater than that in coughing. What mechanism causes this airflow difference? Many authors described that pharyngeal and/or tongue movements are responsible for this difference (Brubaker, 1919; Korpas and Tomori, 1979). However, there are no published reports which prove this theory. To identify the upper airway mechanism responsible for this airflow difference, we compared the activities of several upper airway muscles during sneezing and coughing in decerebrate cats. Although the neural mechanism of coughing has been well documented, much less is known about sneezing (Shannon et al., 1996). To investigate the neural
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mechanism of sneezing, we need to record neuronal activities in the brainstem during sneezing. However, movement of the brainstem due to the sneezing action disturbs the cell recordings. Fictive behavior models in paralyzed animals (Miller et al., 1987; Bolser, 1991; Gre´lot and Milano, 1991; Shiba et al., 1996; Umezaki et al., 1998) allow stable neuronal recording and simplify the analysis of neuronal activities by eliminating several feedback inputs of actual behaviors. To establish a ‘fictive sneezing’ model, we compared respiratory and tongue motor outputs during stimulation of the nasal afferent in paralyzed cats with those in non-paralyzed cats, based on the former part of this study.
2. Materials and methods All the procedures used in this study conform to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Studies were conducted on 13 adult cats of either sex weighing 2.3–4.8 kg. The cats were initially anesthetized with halothane vaporized in nitrous oxide and oxygen, and surgically decerebrated at the mid-collicular level after bilateral ligation of the common carotid arteries. The trachea was cannulated using a T-shaped tube, from which the subglottic pressure and end-tidal CO2 were monitored. Cannulae were placed in the femoral artery to monitor the blood pressure and in the femoral vein for administration of muscle relaxant and physiological saline when necessary. The animals were placed in a stereotaxic frame. Rectal temperature was kept at 36–37.5°C using a heating lamp. Anesthesia was discontinued following the completion of all surgical procedures and at least one hour prior to data collection. At the end of each experiment, the animal was euthanized by an overdose of sodium pentobarbital. Sneezing and coughing were induced by electrical stimulation of the anterior ethmoidal nerve (AEN) (duration, 0.2–0.7 ms; intensity, 200 – 600 mA; frequency, 10–20) (Batsel and Lines, 1975) and the superior laryngeal nerve (SLN) (duration, 0.2 ms; intensity, 40 – 300 mA; frequency, 2 – 10) (Bolser, 1991; Gre´lot and Milano, 1991), lasting for 10 – 20 s so as to obtain the reflex respectively. Bipolar cuff electrodes were placed around the AEN and SLN for stimulation. To monitor upper airway motor outputs, electromyograms (EMGs) were recorded using bipolar stainless steel wire electrodes (50 mm in diameter) implanted into the diaphragm, external oblique abdominus, superior pharyngeal constrictor (SPC), levator veli palatini (LP; soft palate elevator), thyroarytenoid (TA; vocal fold adductor), and styloglossus (SG; elevator of the back of the tongue) muscles.
After recording EMGs, nine cats were paralyzed with gallamine triethiodide (initial injection of 10 mg/kg i.v., maintained by hourly injections of 5 mg/kg) and artificially ventilated with room air (18–24 cycles/min). Endtidal CO2 was typically kept between 3.5 and 5.0%. Bipolar cuff electrodes were placed around the C5 phrenic and L1 abdominal muscle nerves. Furthermore, to assess the tongue activity, we recorded the activity of the whole hypoglossal nerve (XII) or the lateral branch of the hypoglossal nerve (lat-XII), which innervates the SG muscle, using the same electrode. The AEN-induced activities of these nerves were compared with the activities of the muscles innervated by these nerves during actual sneezing induced before paralysis. Signals of muscle and nerve activities were stored on a magnetic tape using a DC to 10 kHz frequency band. To estimate muscle activity, EMG signals, sampled at 1000 Hz using a CED 1401-plus data interface and Spike 2 software (CED, Cambridge, England), were digitally rectified and integrated. The muscle activity was defined as the integrated EMG value per second, averaged from five episodes of sneezing or coughing in a cat. The muscle activity is analyzed from the onset to the secession of activation. When a muscle was silent or its activity was obscure, its activity was analyzed from the beginning of the compression phase to the end of the expulsion phase. Statistical evaluation was performed using Student’s t-test. Differences were considered significant when the probability was less than 0.05.
3. Results Sneezing and coughing were induced in 11 and eight cats, respectively. For six cats in which both sneezing and coughing were induced, the activities of the upper airway muscles were compared between sneezing and coughing. Fig. 1 shows the respiratory and upper airway muscle activities during sneezing and coughing. The respiratory and laryngeal motor patterns during sneezing were similar to that during coughing. Both actions began with diaphragm excitation (inspiration phase). Subsequently, both the abdominal and TA muscles were activated (compression phase). Finally, the abdominal muscle activation continued, usually without TA muscle activation (expulsion phase). The TA muscle activity sometimes lasted until the cessation of the abdominal muscle activity; however, maximal activation of the TA muscle tended to occur before the mid point of the period of abdominal muscle excitation. The main difference in the upper airway motor outputs between sneezing and coughing was the activity of the SG muscle, which was abruptly and strongly activated during the expulsion phase of sneezing, whereas it was virtually silent during coughing. Activation of the SG muscle sometimes started to began before the com-
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Fig. 1. Electromyograms (EMGs) of the diaphragm (DIA), external oblique abdominus (EO), thyroarytenoid (TA), styloglossus (SG), superior pharyngeal constrictor (SPC), and levator veli palatini (LP) muscles in eupnea (A), during sneezing (B) induced by stimulation of the anterior ethmoidal nerve (AEN) (200 ms, 10 Hz), and coughing (C) induced by stimulation of the superior laryngeal nerve (SLN) (100 ms, 3 Hz). Sneezing and coughing episodes are indicated by the arrowheads. The gain of the EMGs in (A) is twice that in (B and C). Calibrations of the subglottic pressure (SP) are 50 cm H2O. Magnifications of the EMGs during sneezing (a), coughing (b), and swallowing (c), obtained during the periods indicated by short horizontal lines (a, b, c) below the LP records, are shown in the square inserts. AEN and SLN stimulation are indicated by thick lines or dots at the bottom of the records. SW: SLN-induced swallowing. These data were obtained in the same cat.
pression phase of sneezing. Even in such cases its activity always peaked during the expulsion phase. During sneezing, the nasopharyngeal closers (SPC and LP muscles) were abruptly and weakly to moderately activated during the compression and expulsion phases. The timing of the activation of these muscles varied between individuals; however, these muscle activities tended to peak at the onset of the expulsion phase. During coughing, these muscles were silent or were weakly activated during the compression and expulsion phases. The activities of these muscles in coughing were significantly weaker than those in sneezing. In
both behaviors, these muscle activities were much weaker than in swallowing. By contrast, the maximal activity of the TA muscle activity in both behaviors was almost the same as that in swallowing. Since our results revealed that SG muscle activity is particularly important for identifying sneezing, we selected the lat-XII, which innervates the SG muscle, for identifying fictive sneezing in paralyzed cats. Fig. 2 shows the respiratory and tongue motor outputs during AEN and SLN stimulation after induction of paralysis. The motor pattern of nerve activities recorded during AEN stimulation was consistent with that of muscle
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Fig. 2. Neurograms of the phrenic nerve (PHR), abdominal nerve (ABD), and hypoglossal nerve (XII), and lateral branch of the hypoglossal nerve (lat-XII) during stimulation of the AEN (A) and SLN (B). The periods of AEN and SLN stimulation are indicated by thick lines at the bottom of the records. Cough-like and swallow-like activities are indicated by arrowheads and SW, respectively. Data in the upper columns (a) and lower columns (b) were obtained from different cats.
activities during actual sneezing induced before paralysis. After paralysis AEN stimulation induced phrenic nerve activation, followed by co-activation of the abdominal nerve and the lat-XII. The onset of lat-XII activation was always later than that of the abdominal nerve. The lat-XII was virtually silent during cough-like activity (Fig. 2Bb). By contrast, the XII was activated not only during sneeze-like activity (Fig. 2Aa) but also during cough-like activity (Fig. 2Ba). The alternation from inspiration to expiration during sneeze-like reflex was usually synchronized with lung inflation as reported by Macron et al. (1994).
4. Discussion The present study shows that tongue movements are the main difference in the upper airway motor outputs between sneezing and coughing. Fig. 3 summarizes the motor patterns of respiratory and upper airway muscles during sneezing and coughing. Before carrying out the present study, we speculated that nasopharyngeal closers worked as an airflow separator. Opening and closing the nasopharynx might assist the expulsive airflow to pass through the nasal cavity in sneezing and through the oral cavity in coughing, respectively. However, the activities of the nasopharyngeal closers in coughing were weaker than in sneezing. Our results also
indicate that strong nasopharyngeal closing, which prevents oropharyngeal contents from invading the nasal cavity during swallowing, did not occur during sneezing or coughing. These results imply that the nasopharyngeal closers play a minor role in the mechanism responsible for the airflow difference. We think that the expulsion airflow in coughing automatically passes mainly through the oral cavity because of the high flow resistance of the nasal cavity, which is about half of the total respiratory resistance (Bartrett, 1986), and that increased oral airway resistance due to tongue back elevation causes a strong nasal airflow during sneezing. We conclude that tongue movement, rather than nasopharyngeal movement, is the primary factor of the mechanism responsible for the expiratory airflow difference between sneezing and coughing. Although nasopharyngeal closers do not function as an airflow separator, it is possible that nasopharyngeal closing at the onset of the expulsion phase of sneezing assists the increase in supraglottic pressure, and that nasopharyngeal opening then produces an explosive airflow to the nasal cavity, in a manner similar to the action of the glottis which increases subglottic pressure and then produces an expulsive airflow to the supraglottic space (Nonaka et al., 1990). In paralyzed animals, electrical stimulation of the AEN caused a sneeze-like reflex. The respiratory and upper airway motor patterns of this response were
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Fig. 3. Schematic illustration of the typical patterns of activities of the respiratory and upper airway muscles during coughing (A), sneezing (B), and swallowing (C). Stages I (inspiration phase), II (compression phase), and III (expulsion phase) of coughing and sneezing are delineated by vertical lines. The hatched area indicates variable muscle activity. Abbreviations are the same as for Fig. 1.
consistent with that of actual sneezing. Thus, we defined this reflex response as ‘fictive sneezing’. We think that the activity of the lat-XII is important for identifying fictive sneezing. Batsel and Lines (1978) defined a sneeze-like reflex using only respiratory neuron activities in paralyzed cats. Wallois et al. (1992, 1997) defined it using phrenic nerve activity or using both phrenic and expiratory muscle nerve activities. It is difficult to discriminate the sneeze-like reflex from other reflexes including sniffing and coughing. We think that an additional recording of the lat-XII is necessary to identify fictive sneezing. Furthermore, the result that the XII and lat-XII were activated and silent during coughing, respectively, means that the medial branch of the hypoglossal nerve is responsible for the cough-induced XII activation. Like other fictive behavior models, the new experimental model of fictive sneezing described in this paper should facilitate the analysis of the brainstem mechanism that produces sneezing.
Acknowledgements We thank Dr Ken Nakazawa for participation in some experiments, and Drs Fumiaki Hayashi and Toshiro Umezaki for comments on the manuscript. This work was supported in part by a Grant-in Aid for Scientific Research from the Japanese Ministry of Education, Science and Culture (No. 09771330).
References Bartrett, D.J., 1986. Upper airway motor systems. In: Cherniack,
N.S., Widdicombe, J.G. (Eds.), Handbook of Physiology: Section 3, The Respiratory System, vol. II. The American Physiological Society, Bethesda, MD, pp. 223 – 245. Batsel, H.L., Lines, A.J., 1975. Neural mechanisms of sneeze. Am. J. Physiol. 229, 770 – 776. Batsel, H.L., Lines, A.J., 1978. Discharge of respiratory neurons in sneezes resulting from ethmoidal nerve stimulation. Exp. Neurol. 58, 410 – 424. Bolser, D.C., 1991. Fictive cough in the cat. J. Appl. Physiol. 71, 2325 – 2331. Brubaker, A.P., 1919. The physiology of sneezing. J. Am. Med. Assoc. 73, 585 – 587. Gre´lot, L., Milano, S., 1991. Diaphragmatic and abdominal muscle activity during coughing in the decerebrate cat. Neuroreport 2, 165 – 168. Korpas, J., Tomori, Z., 1979. Cough and Other Respiratory Reflexes. S. Karger, Basel. Macron, J.M., Wallois, F., Duron, B., 1994. Influence of vagal afferents in the sneeze reflex in cats. Neurosci. Lett. 177, 79–82. Miller, A.D., Tan, L.K., Suzuki, I., 1987. Control of abdominal and expiratory intercostal muscle activity during vomiting: role of ventral respiratory group expiratory neurons. J. Neurophysiol. 57, 1854 – 1866. Nonaka, S., Unno, T., Ohta, Y., Mori, S., 1990. Sneeze-evoking region within the brainstem. Brain Res. 511, 265 – 270. Shannon, R., Bolser, D.C., Lindsey, B.G., 1996. Neural control of coughing and sneezing. In: Miller, A.D., Bianchi, A.L., Bishop, B.P. (Eds.), Neural Control of the Respiratory Muscles. CRC press, Boca Raton, FL, pp. 213 – 222. Shiba, K., Umezaki, T., Zheng, Y., Miller, A.D., 1996. Fictive vocalization in the cat. Neuroreport 7, 2139 – 2142. Umezaki, T., Shiba, K., Zheng, Y., Miller, A.D., 1998. Upper airway motor outputs during vomiting versus swallowing in the decerebrate cat. Brain Res. 781, 25 – 36. Wallois, F., Bodineau, L., Macron, J.M., Marlot, D., Duron, B., 1997. Role of respiratory and non-respiratory neurones in the region of the NTS in the elaboration of the sneeze reflex in cat. Brain Res. 768, 71 – 85. Wallois, F., Macron, J.M., Jounieaux, V., Duron, B., 1992. Influence of trigeminal nasal afferents on bulbar respiratory neuronal activity. Brain Res. 599, 105 – 116.
Upper airway motor outputs during sneezing and coughing in decerebrate cats Isamu Satoh a,*, Keisuke Shiba a, Nobuhiro Kobayashi a, Yoshio Nakajima b, Akiyoshi Konno a a
Department of Otolaryngology, School of Medicine, Chiba Uni6ersity, 1 -8 -1 Inohana, Chiba 260 -8670, Japan b Department of Physiology, School of Medicine, Chiba Uni6ersity, 1 -8 -1 Inohana, Chiba 260 -8670, Japan Received 19 February 1998; accepted 21 July 1998
Abstract The purposes of the present study were to determine which upper airway movements cause a difference in the expiratory airflow pathway between sneezing and coughing, and to develop a new animal model for studying the neural mechanism of sneezing in paralyzed animals, i.e. fictive sneezing. We compared the upper airway motor patterns of sneezing and coughing, induced by electrical stimulation of the anterior ethmoidal nerve (AEN) and superior laryngeal nerve, respectively, in non-paralyzed decerebrate cats. Respiratory and laryngeal motor patterns that consisted of an inspiration phase, compression phase, and expulsion phase were observed for both sneezing and coughing. The main difference was observed in the activity of the elevator of the back of the tongue, styloglossus (SG) muscle, which was explosively activated during the expulsion phase of sneezing, whereas it was virtually silent during coughing. The nasopharyngeal closers were weakly to moderately activated during sneezing. Their activities during coughing were weaker than during sneezing. Furthermore, the AEN-induced activities of the phrenic and abdominal nerves and the lateral branch of the hypoglossal nerve (lat-XII), which innervates the SG muscle, in paralyzed cats were consistent with the activities of the diaphragm, abdominal, and SG muscles during actual sneezing in non-paralyzed cats. Thus, we conclude that tongue movement is the main difference in the motor outputs between sneezing and coughing, which probably causes greater nasal airflow in sneezing, and that it is necessary to record the activity of the lat-XII to identify fictive sneezing in paralyzed cats. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Sneeze; Cough; Upper airway reflex; Styloglossus muscle; Hypoglossal nerve; Fictive sneezing; Cat
1. Introduction Sneezing and coughing, induced by stimulation of the nasal and laryngeal mucosae respectively, are defensive reflexes of the airways. Both reflexes consist of an inspiration phase, compression phase, in which powerful expiratory effort with vocal fold adduction abruptly increases the subglottic pressure, and expulsion phase, in which continuous expiratory effort with vocal fold abduction causes explosive airflow (Korpas and Tomori, 1979). The main difference between sneezing and * Corresponding author. Tel.: + 81-43-2227171, ext. 5102; Fax: +81-43-2262028; e-mail: [email protected].
coughing is that the expiratory nasal airflow in sneezing is much greater than that in coughing. What mechanism causes this airflow difference? Many authors described that pharyngeal and/or tongue movements are responsible for this difference (Brubaker, 1919; Korpas and Tomori, 1979). However, there are no published reports which prove this theory. To identify the upper airway mechanism responsible for this airflow difference, we compared the activities of several upper airway muscles during sneezing and coughing in decerebrate cats. Although the neural mechanism of coughing has been well documented, much less is known about sneezing (Shannon et al., 1996). To investigate the neural
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mechanism of sneezing, we need to record neuronal activities in the brainstem during sneezing. However, movement of the brainstem due to the sneezing action disturbs the cell recordings. Fictive behavior models in paralyzed animals (Miller et al., 1987; Bolser, 1991; Gre´lot and Milano, 1991; Shiba et al., 1996; Umezaki et al., 1998) allow stable neuronal recording and simplify the analysis of neuronal activities by eliminating several feedback inputs of actual behaviors. To establish a ‘fictive sneezing’ model, we compared respiratory and tongue motor outputs during stimulation of the nasal afferent in paralyzed cats with those in non-paralyzed cats, based on the former part of this study.
2. Materials and methods All the procedures used in this study conform to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Studies were conducted on 13 adult cats of either sex weighing 2.3–4.8 kg. The cats were initially anesthetized with halothane vaporized in nitrous oxide and oxygen, and surgically decerebrated at the mid-collicular level after bilateral ligation of the common carotid arteries. The trachea was cannulated using a T-shaped tube, from which the subglottic pressure and end-tidal CO2 were monitored. Cannulae were placed in the femoral artery to monitor the blood pressure and in the femoral vein for administration of muscle relaxant and physiological saline when necessary. The animals were placed in a stereotaxic frame. Rectal temperature was kept at 36–37.5°C using a heating lamp. Anesthesia was discontinued following the completion of all surgical procedures and at least one hour prior to data collection. At the end of each experiment, the animal was euthanized by an overdose of sodium pentobarbital. Sneezing and coughing were induced by electrical stimulation of the anterior ethmoidal nerve (AEN) (duration, 0.2–0.7 ms; intensity, 200 – 600 mA; frequency, 10–20) (Batsel and Lines, 1975) and the superior laryngeal nerve (SLN) (duration, 0.2 ms; intensity, 40 – 300 mA; frequency, 2 – 10) (Bolser, 1991; Gre´lot and Milano, 1991), lasting for 10 – 20 s so as to obtain the reflex respectively. Bipolar cuff electrodes were placed around the AEN and SLN for stimulation. To monitor upper airway motor outputs, electromyograms (EMGs) were recorded using bipolar stainless steel wire electrodes (50 mm in diameter) implanted into the diaphragm, external oblique abdominus, superior pharyngeal constrictor (SPC), levator veli palatini (LP; soft palate elevator), thyroarytenoid (TA; vocal fold adductor), and styloglossus (SG; elevator of the back of the tongue) muscles.
After recording EMGs, nine cats were paralyzed with gallamine triethiodide (initial injection of 10 mg/kg i.v., maintained by hourly injections of 5 mg/kg) and artificially ventilated with room air (18–24 cycles/min). Endtidal CO2 was typically kept between 3.5 and 5.0%. Bipolar cuff electrodes were placed around the C5 phrenic and L1 abdominal muscle nerves. Furthermore, to assess the tongue activity, we recorded the activity of the whole hypoglossal nerve (XII) or the lateral branch of the hypoglossal nerve (lat-XII), which innervates the SG muscle, using the same electrode. The AEN-induced activities of these nerves were compared with the activities of the muscles innervated by these nerves during actual sneezing induced before paralysis. Signals of muscle and nerve activities were stored on a magnetic tape using a DC to 10 kHz frequency band. To estimate muscle activity, EMG signals, sampled at 1000 Hz using a CED 1401-plus data interface and Spike 2 software (CED, Cambridge, England), were digitally rectified and integrated. The muscle activity was defined as the integrated EMG value per second, averaged from five episodes of sneezing or coughing in a cat. The muscle activity is analyzed from the onset to the secession of activation. When a muscle was silent or its activity was obscure, its activity was analyzed from the beginning of the compression phase to the end of the expulsion phase. Statistical evaluation was performed using Student’s t-test. Differences were considered significant when the probability was less than 0.05.
3. Results Sneezing and coughing were induced in 11 and eight cats, respectively. For six cats in which both sneezing and coughing were induced, the activities of the upper airway muscles were compared between sneezing and coughing. Fig. 1 shows the respiratory and upper airway muscle activities during sneezing and coughing. The respiratory and laryngeal motor patterns during sneezing were similar to that during coughing. Both actions began with diaphragm excitation (inspiration phase). Subsequently, both the abdominal and TA muscles were activated (compression phase). Finally, the abdominal muscle activation continued, usually without TA muscle activation (expulsion phase). The TA muscle activity sometimes lasted until the cessation of the abdominal muscle activity; however, maximal activation of the TA muscle tended to occur before the mid point of the period of abdominal muscle excitation. The main difference in the upper airway motor outputs between sneezing and coughing was the activity of the SG muscle, which was abruptly and strongly activated during the expulsion phase of sneezing, whereas it was virtually silent during coughing. Activation of the SG muscle sometimes started to began before the com-
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Fig. 1. Electromyograms (EMGs) of the diaphragm (DIA), external oblique abdominus (EO), thyroarytenoid (TA), styloglossus (SG), superior pharyngeal constrictor (SPC), and levator veli palatini (LP) muscles in eupnea (A), during sneezing (B) induced by stimulation of the anterior ethmoidal nerve (AEN) (200 ms, 10 Hz), and coughing (C) induced by stimulation of the superior laryngeal nerve (SLN) (100 ms, 3 Hz). Sneezing and coughing episodes are indicated by the arrowheads. The gain of the EMGs in (A) is twice that in (B and C). Calibrations of the subglottic pressure (SP) are 50 cm H2O. Magnifications of the EMGs during sneezing (a), coughing (b), and swallowing (c), obtained during the periods indicated by short horizontal lines (a, b, c) below the LP records, are shown in the square inserts. AEN and SLN stimulation are indicated by thick lines or dots at the bottom of the records. SW: SLN-induced swallowing. These data were obtained in the same cat.
pression phase of sneezing. Even in such cases its activity always peaked during the expulsion phase. During sneezing, the nasopharyngeal closers (SPC and LP muscles) were abruptly and weakly to moderately activated during the compression and expulsion phases. The timing of the activation of these muscles varied between individuals; however, these muscle activities tended to peak at the onset of the expulsion phase. During coughing, these muscles were silent or were weakly activated during the compression and expulsion phases. The activities of these muscles in coughing were significantly weaker than those in sneezing. In
both behaviors, these muscle activities were much weaker than in swallowing. By contrast, the maximal activity of the TA muscle activity in both behaviors was almost the same as that in swallowing. Since our results revealed that SG muscle activity is particularly important for identifying sneezing, we selected the lat-XII, which innervates the SG muscle, for identifying fictive sneezing in paralyzed cats. Fig. 2 shows the respiratory and tongue motor outputs during AEN and SLN stimulation after induction of paralysis. The motor pattern of nerve activities recorded during AEN stimulation was consistent with that of muscle
134
I. Satoh et al. / Neuroscience Research 32 (1998) 131–135
Fig. 2. Neurograms of the phrenic nerve (PHR), abdominal nerve (ABD), and hypoglossal nerve (XII), and lateral branch of the hypoglossal nerve (lat-XII) during stimulation of the AEN (A) and SLN (B). The periods of AEN and SLN stimulation are indicated by thick lines at the bottom of the records. Cough-like and swallow-like activities are indicated by arrowheads and SW, respectively. Data in the upper columns (a) and lower columns (b) were obtained from different cats.
activities during actual sneezing induced before paralysis. After paralysis AEN stimulation induced phrenic nerve activation, followed by co-activation of the abdominal nerve and the lat-XII. The onset of lat-XII activation was always later than that of the abdominal nerve. The lat-XII was virtually silent during cough-like activity (Fig. 2Bb). By contrast, the XII was activated not only during sneeze-like activity (Fig. 2Aa) but also during cough-like activity (Fig. 2Ba). The alternation from inspiration to expiration during sneeze-like reflex was usually synchronized with lung inflation as reported by Macron et al. (1994).
4. Discussion The present study shows that tongue movements are the main difference in the upper airway motor outputs between sneezing and coughing. Fig. 3 summarizes the motor patterns of respiratory and upper airway muscles during sneezing and coughing. Before carrying out the present study, we speculated that nasopharyngeal closers worked as an airflow separator. Opening and closing the nasopharynx might assist the expulsive airflow to pass through the nasal cavity in sneezing and through the oral cavity in coughing, respectively. However, the activities of the nasopharyngeal closers in coughing were weaker than in sneezing. Our results also
indicate that strong nasopharyngeal closing, which prevents oropharyngeal contents from invading the nasal cavity during swallowing, did not occur during sneezing or coughing. These results imply that the nasopharyngeal closers play a minor role in the mechanism responsible for the airflow difference. We think that the expulsion airflow in coughing automatically passes mainly through the oral cavity because of the high flow resistance of the nasal cavity, which is about half of the total respiratory resistance (Bartrett, 1986), and that increased oral airway resistance due to tongue back elevation causes a strong nasal airflow during sneezing. We conclude that tongue movement, rather than nasopharyngeal movement, is the primary factor of the mechanism responsible for the expiratory airflow difference between sneezing and coughing. Although nasopharyngeal closers do not function as an airflow separator, it is possible that nasopharyngeal closing at the onset of the expulsion phase of sneezing assists the increase in supraglottic pressure, and that nasopharyngeal opening then produces an explosive airflow to the nasal cavity, in a manner similar to the action of the glottis which increases subglottic pressure and then produces an expulsive airflow to the supraglottic space (Nonaka et al., 1990). In paralyzed animals, electrical stimulation of the AEN caused a sneeze-like reflex. The respiratory and upper airway motor patterns of this response were
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Fig. 3. Schematic illustration of the typical patterns of activities of the respiratory and upper airway muscles during coughing (A), sneezing (B), and swallowing (C). Stages I (inspiration phase), II (compression phase), and III (expulsion phase) of coughing and sneezing are delineated by vertical lines. The hatched area indicates variable muscle activity. Abbreviations are the same as for Fig. 1.
consistent with that of actual sneezing. Thus, we defined this reflex response as ‘fictive sneezing’. We think that the activity of the lat-XII is important for identifying fictive sneezing. Batsel and Lines (1978) defined a sneeze-like reflex using only respiratory neuron activities in paralyzed cats. Wallois et al. (1992, 1997) defined it using phrenic nerve activity or using both phrenic and expiratory muscle nerve activities. It is difficult to discriminate the sneeze-like reflex from other reflexes including sniffing and coughing. We think that an additional recording of the lat-XII is necessary to identify fictive sneezing. Furthermore, the result that the XII and lat-XII were activated and silent during coughing, respectively, means that the medial branch of the hypoglossal nerve is responsible for the cough-induced XII activation. Like other fictive behavior models, the new experimental model of fictive sneezing described in this paper should facilitate the analysis of the brainstem mechanism that produces sneezing.
Acknowledgements We thank Dr Ken Nakazawa for participation in some experiments, and Drs Fumiaki Hayashi and Toshiro Umezaki for comments on the manuscript. This work was supported in part by a Grant-in Aid for Scientific Research from the Japanese Ministry of Education, Science and Culture (No. 09771330).
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