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Differential Effects of Kainic Acid Lesions in Medullary Raphe on Cough and Sneeze in Anesthetized Rabbits

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Neurobiology of Respiration

Abstract

The effects of microinjections of the excitatory neurotoxin kainic acid (2 mg/ml; 49 ± 1 nl) on the mechanically induced tracheobronchial cough, sneeze, and solitary expulsions from the trachea were examined in 11 anesthetized rabbits. Kainic acid was injected into the medulla (1.6–2.8 mm rostral to the obex, 1.4–1.6 and 2.9–3.2 mm below the dorsal medullary surface). Blood pressure, esophageal pressure (EP), and electromyograms (EMGs) of the diaphragm (DIA) and abdominal muscles (ABD) were recorded. Kainic acid reduced the number of coughs (means ± SE) from 3.8 ± 2.0 to 0.9 ± 0.7 (p = 0.016), the amplitude of DIA cough from 90 ± 11 to 42 ± 13 % (p = 0.004), ABD EMG moving average from 103 ± 9 to 37 ± 15 % (p = 0.006), and inspiratory from 0.67 ± 0.13 to 0.36 ± 0.12 kPa (p = 0.013) and expiratory EP from 1.70 ± 0.54 to 0.89 ± 0.46 kPa (p = 0.008). Kainic acid had no effect on the number of sneeze reflexes nor did it affect solitary expulsions from the trachea. These effects were accompanied by significant increases in systemic blood pressure and respiratory rate. Spatiotemporal analysis of the cough and sneeze reflexes revealed increases in the duration of cough active expiratory phase, in the intervals between maxima of DIA and ABD EMG discharges, and in the active portion of total cough phase duration. Our findings suggest a diverse role of raphe neurons in the central control of motor airway responses such as coughing and sneezing. A complex function of raphe neurons in the generation of the cough motor pattern also is suggested.

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References

  • Bianchi, A. L., Denavit-Saubie, M., & Champagnat, J. (1995). Central control of breathing in mammals: Neuronal circuitry, membrane properties, and neurotransmitters. Physiological Reviews, 75(1), 1–45.

    PubMed  CAS  Google Scholar 

  • Billig, I., Foris, J. M., Card, J. P., & Yates, B. J. (1999). Transneuronal tracing of neural pathways controlling an abdominal muscle, rectus abdominis, in the ferret. Brain Research, 820(1–2), 31–44.

    Article  PubMed  CAS  Google Scholar 

  • Bolser, D. C., Davenport, P. W., Golder, F. J., Baekey, D. M., Morris, K. F., Lindsey, B. G., & Shannon, R. (2003). Neurogenesis of cough. In K. F. Chung, J. G. Widdicombe, & H. A. Boushey (Eds.), Cough: Causes, mechanisms and therapy (pp. 173–180). Malden/Oxford/Carlton: Blackwell Publishing.

    Chapter  Google Scholar 

  • Bolser, D. C., Poliaček, I., Jakuš, J., Fuller, D. D., & Davenport, P. W. (2006). Neurogenesis of cough, other airway defensive behaviors and breathing. A holarchical system? Respiratory Physiology & Neurobiology, 152(3), 255–265.

    Article  Google Scholar 

  • Coyle, J. T., Molliver, M. E., & Kuhar, M. J. (1978). In situ injection of kainic acid: A new method for selectively lesioning neural cell bodies while sparing axons of passage. Journal of Comparative Neurology, 180(2), 301–323.

    Article  PubMed  CAS  Google Scholar 

  • Felten, D. L., & Cummings, J. P. (1979). The raphe nuclei of the rabbit brain stem. Journal of Comparative Neurology, 187(1), 199–243.

    Article  PubMed  CAS  Google Scholar 

  • Jakus, J., Stránsky, A., Poliacek, I., Baráni, H., & Bošeľová, L. (1998). Effects of medullary midline lesions on cough and other airway reflexes in anaesthetized cat. Physiological Research, 47(3), 203–213.

    PubMed  CAS  Google Scholar 

  • Jakus, J., Tomori, Z., Stránsky, A., & Boselová, L. (1987). Bulbar respiratory activity during defensive airways reflexes in cats. Acta Physiologica Hungarica, 70(2–3), 245–254.

    PubMed  CAS  Google Scholar 

  • Jakuš, J., Tomori, Z., & Stránsky, A. (2004). Neuronal determinants of breathing, coughing and related motor behaviours (p. 355). Martin: Wist.

    Google Scholar 

  • Lindsey, B. G., Segers, L. S., Morris, K. F., Hernandez, Y. M., Saporta, S., & Shannon, R. (1994). Distributed actions and dynamic associations in respiratory-related neuronal assemblies of the ventrolateral medulla and brain stem midline: Evidence from spike train analysis. Journal of Neurophysiology, 72(4), 1830–1851.

    PubMed  CAS  Google Scholar 

  • Lindsey, B. G., Arata, A., Morris, K. F., Hernandez, Y. M., & Shannon, R. (1998). Medullary raphe neurones and baroreceptor modulation of the respiratory motor pattern in the cat. Journal of Neurophysiology, 512, 863–882.

    CAS  Google Scholar 

  • Lindsey, B. G., Morris, K. F., Segers, L. S., & Shannon, R. (2000). Respiratory neuronal assemblies. Respiratory Physiology, 122(2–3), 183–196.

    Article  CAS  Google Scholar 

  • Manzke, T., Guenther, U., Ponimaskin, E. G., Haller, M., Dutschmann, M., Schwarzacher, S., & Richter, D. W. (2003). 5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia. Science, 301(5630), 226–229.

    Article  PubMed  CAS  Google Scholar 

  • Nuding, S. C., Segers, L. S., Shannon, R., O’Connor, R., Morris, K. F., & Lindsey, B. G. (2009). Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 364(1529), 2501–2516.

    Article  PubMed  Google Scholar 

  • Peever, J. H., Necakov, A., & Duffin, J. (2001). Nucleus raphe obscurus modulateshypoglossal output of neonatal rat in vitro transverse brain stem slices. Journal of Applied Physiology, 90, 269–279.

    PubMed  CAS  Google Scholar 

  • Poliacek, I., Jakus, J., Knociková, J., Baráni, H., Halašová, E., & Višňovcová, N. (2008). Medullary raphe midline is involved in production of expulsive expirations in anesthetized rabbits. Journal of Physiology and Pharmacology, 59(Suppl 6), 597–605.

    PubMed  Google Scholar 

  • Poliacek, I., Simera, M., Veternik, M., Machac, P., Barani, H., Visnovcova, N., Halasova, E., & Jakus, J. (2012). Contribution of medullary raphé to control of coughing-Codeine trials in cat. Respiratory Physiology & Neurobiology, 184(1), 106–112.

    Article  Google Scholar 

  • Ptak, K., Yamanishi, T., Aungst, J., Milescu, L. S., Zhang, R., Richerson, G. B., & Smith, J. C. (2009). Raphé neurons stimulate respiratory circuit activity by multiple mechanisms via endogenously released serotonin and substance P. Journal of Neuroscience, 29(12), 3720–3737.

    Article  PubMed  CAS  Google Scholar 

  • Sessle, B. J., Ball, G. J., & Lucier, G. E. (1981). Suppressive influences from periaqueductal gray and nucleus raphe on respiration and related reflex activities and on solitary tract neurons, and effect of naloxone. Brain Research, 216, 145–161.

    Article  PubMed  CAS  Google Scholar 

  • Shannon, R., Baekey, D. M., Morris, K. F., Nuding, S. C., Segers, L. S., & Lindsey, B. G. (2004). Production of reflex cough by brainstem respiratory networks. Pulmonary Pharmacology and Therapeutics, 17, 369–376.

    Article  PubMed  CAS  Google Scholar 

  • Smith, J. C., Abdala, A. P. L., Koizumi, H., Rybak, I. A., & Paton, J. F. R. (2007). Spatial and functional architecture of the mammalian brainstem respiratory network: A hierarchy of three oscillatory mechanisms. Journal of Neurophysiology, 98, 3370–3387.

    Article  PubMed  CAS  Google Scholar 

  • Wang, G., Yu, S., Zhang, F., Li, Y., Cao, Y., Li, Q., Song, G., & Zhang, H. (2004). Modulation of inspiratory inhibition of the Bötzinger complex by raphe pallidus and locus coeruleus in rabbits. Advances in Experimental Medicine and Biology, 551, 127–133.

    Article  PubMed  Google Scholar 

  • Wang, C., Saha, S., Rose, M. J., Davenport, P. W., & Bolser, D. C. (2009). Spatiotemporal regulation of the cough motor pattern. Cough, 5, 12.

    Article  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge the technical assistance Iveta Najslova, Ing. Peter Machac, and Mgr. Ivana Šimerová. Supported by VEGA grants 1/0038/09 and 1/0126/12, and co-financed from the European Regional Developmental Fund. In addition, this work also was in part supported by the Slovak Research and Development Agency contract No. APVV-0189-11.

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The authors declare no conflicts of interest in relation to this article.

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Correspondence to M. Simera .

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Simera, M. et al. (2013). Differential Effects of Kainic Acid Lesions in Medullary Raphe on Cough and Sneeze in Anesthetized Rabbits. In: Pokorski, M. (eds) Neurobiology of Respiration. Advances in Experimental Medicine and Biology, vol 788. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6627-3_6

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