Salivary alpha-amylase activity—An indicator of relaxation response in perioperative patients
Affiliation(s)
Department of Nursing, Saku University, Saku, Japan. Graduate School of Health Science, Gunma University, Maebashi, Japan.
Department of Nursing, Saku University, Saku, Japan. Graduate School of Health Science, Gunma University, Maebashi, Japan.
ABSTRACT
The psychological stress of most perioperative patients has been reduced by many interventions. In order to evaluate the effects of these interventions, biomarkers are being considered as objective assessment tools in addition to the subjective assessment tools. It has been thought that salivary α-amylase (sAA) activity is associated with sympathetic nervous system activity, which reflects psychological stress. We examined the relationship between sAA, self-reported data, and autonomic nervous system activity to assess the reliability of sAA as a marker for relaxing response in surgery-related stress. The sAA, the State anxiety, Visual Analogue Scale (VAS) of pain, and heart rate variability were used to assess prior to and after the relaxation on the day before surgery, and on postoperative days (POD) 1, 2, 3, and 7. A total of 75 patients participated and 301 relaxing response readings were obtained. We found that the sAA significantly decreased depending upon the pain and anxiety by relaxation, but they were unrelated to sympathetic nervous system activity. There was weak correlation between the change in sAA, and anxiety and VAS pain. Thus, sAA appears to be an easy-to-use, non-invasive and good marker for relaxing response within a short period in surgery-related stress patients.
The psychological stress of most perioperative patients has been reduced by many interventions. In order to evaluate the effects of these interventions, biomarkers are being considered as objective assessment tools in addition to the subjective assessment tools. It has been thought that salivary α-amylase (sAA) activity is associated with sympathetic nervous system activity, which reflects psychological stress. We examined the relationship between sAA, self-reported data, and autonomic nervous system activity to assess the reliability of sAA as a marker for relaxing response in surgery-related stress. The sAA, the State anxiety, Visual Analogue Scale (VAS) of pain, and heart rate variability were used to assess prior to and after the relaxation on the day before surgery, and on postoperative days (POD) 1, 2, 3, and 7. A total of 75 patients participated and 301 relaxing response readings were obtained. We found that the sAA significantly decreased depending upon the pain and anxiety by relaxation, but they were unrelated to sympathetic nervous system activity. There was weak correlation between the change in sAA, and anxiety and VAS pain. Thus, sAA appears to be an easy-to-use, non-invasive and good marker for relaxing response within a short period in surgery-related stress patients.
Cite this paper
Minowa, C. and Koitabashi, K. (2012) Salivary alpha-amylase activity—An indicator of relaxation response in perioperative patients. Open Journal of Nursing, 2, 208-214. doi: 10.4236/ojn.2012.23032.
Minowa, C. and Koitabashi, K. (2012) Salivary alpha-amylase activity—An indicator of relaxation response in perioperative patients. Open Journal of Nursing, 2, 208-214. doi: 10.4236/ojn.2012.23032.
References
[1] Leinonen, T. and Leino-Kilpi, H. (1999) Research in peri-operative nursing care. Journal of Clinical Nursing, 8, 123-138. doi:10.1046/j.1365-2702.1999.00239.x [2] Johansson, K., Nuutila, L., Virtanen, H., Katajisto, J. and Salanter?, S. (2005) Preoperative education for orthopaedic patients: Systematic review. Journal of Advanced Nursing, 50, 212-223. doi:10.1111/j.1365-2648.2005.03381.x [3] Roykulcharoen, V. and Good, M. (2004) Systematic relaxation to relieve postoperative pain. Journal of Advanced Nursing, 48, 140-148. doi:10.1111/j.1365-2648.2004.03181.x [4] Seers, K. and Carroll, D. (1998) Relaxation techniques for acute pain management: A systematic review. Journal of Advanced Nursing, 27, 466-475. doi:10.1046/j.1365-2648.1998.00538.x [5] Montgomery, G.H., Bovbjerg, D.H., Schnur, J.B., David, D., Goldfarb, A., Weltz, C.R., Schechter, C., Graff-Zivin, J., Tatrow, K., Price, D.D. and Silverstein, J.H. (2007) A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients. Journal of the National Cancer Institute, 99, 1304-1312. doi:10.1093/jnci/djm106 [6] Bauer, B.A., Cutshall, S.M., Wentworth, L.J., Engen, D., Messner, P.K., Wood, C.M., Brekke, K.M., Kelly, R.F. and Sundt, T.M. (2010) Effect of massage therapy on pain, anxiety, and tension after cardiac surgery: A randomized study. Complementary Therapies in Clinical Practice, 16, 70-75. doi:10.1016/j.ctcp.2009.06.012 [7] Yamaguchi, M., Kanemaru, M., Kanemori, T. and Mizuno, Y. (2003) Flow-injection-type biosensor system for salivary amylase activity. Biosensors & Bioelectronics, 18, 835-840. doi:10.1016/S0956-5663(03)00007-1 [8] Benson, H. and Klipper, M.Z. (2001) The relaxation response. Harper Collins Publishers Inc., New York. [9] Nater, U.M. and Rohleder, N. (2009) Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: Current state of research. Psychoneuroendocrinology, 34, 486-496. doi:10.1016/j.psyneuen.2009.01.014 [10] Proctor, G.B. and Carpenter, G.H. (2007) Regulation of salivary gland function by autonomic nerves. Autonomic Neuroscience, 133, 3-18. doi:10.1016/j.autneu.2006.10.006 [11] Chatterton, R.T. Jr., Vogelsong, K.M., Lu, Y.C. and Hudgens, G.A. (1997) Hormonal responses to psychological stress in men preparing for skydiving. The Journal of Clinical Endocrinology and Metabolism, 82, 2503-2509. doi:10.1210/jc.82.8.2503 [12] Bosch, J.A., De Geus, E.J.C., Veerman, E.C.I., Hoogstraten, J. and Amerongen, A.V.N. (2003) Innate secretory immunity in response to laboratory stressors that evoke distinct patterns of cardiac autonomic activity. Psychosomatic Medicine, 65, 245-258 doi:10.1097/01.PSY.0000058376.50240.2D [13] Skosnik, P.D., Chatterton, R.T. Jr., Swisher, T. and Park, S. (2000) Modulation of attentional inhibition by norepinephrine and cortisol after psychological stress. International Journal of Psychophysiology, 36, 59-68. doi:10.1016/S0167-8760(99)00100-2 [14] Morrison, W.E., Haas, E.C., Shaffner, D.H., Garrett, E.S. and Fackler, J.C. (2003) Noise, stress, and annoyance in a pediatric intensive care unit. Critical Care Medicine, 31, 113-119. doi:10.1097/00003246-200301000-00018 [15] Nater, U.M., Rohleder, N., Gaab, J., Bergera, S., Juda, A., Kirschbaum, C. and Ehlert, U. (2005) Human salivary α-amylase reactivity in a psychosocial stress paradigm. International Journal of Psychophysiology, 55, 333-342. doi:10.1016/j.ijpsycho.2004.09.009 [16] Noto, Y., Sato, T., Kudo, M., Kurata, K. and Hirota, K. (2005) The relationship between salivary biomarkers and state-trait anxiety inventory score under mental arithmetic stress: A pilot study. Anesthesia and Analgesia, 101, 1873-1876.doi:10.1213/01.ANE.0000184196.60838.8D [17] Takai, N., Yamaguchi, Y., Aragakia, T., Eto, K., Uchihashia, K. and Nishikawa, Y. (2004) Effect of psychological stress on the salivary cortisol and amylase levels in healthy young adults. Archives of Oral Biology, 49, 963-968. doi:10.1016/j.archoralbio.2004.06.007 [18] Shirasaki, S., Fujii, H., Takahashi, M., Sato, T., Ebina, M., Noto, Y. and Hirota, K. (2007) Correlation between salivary α-amylase activity and pain scale in patients with chronic pain. Regional Anesthesia and Pain Medicine, 32, 120-123. doi:10.1016/j.rapm.2006.11.008 [19] Hodgson, N.A. and Andersen, S. (2008) The clinical efficacy of reflexology in nursing home residents with dementia. Journal of Alternative and Complementary Medicine, 14, 269-275. doi:10.1089/acm.2007.0577 [20] Arai, Y.-C.P., Sakakibara, S., Ito A., Ohshima, K., Sakakibara, T., Nishi, T., Hibino, S., Niwa, S. and Kuniyoshi, K. (2008) Intra-operative natural sound decreases salivary amylase activity of patients undergoing inguinal hernia repair under epidural anesthesia. Acta Anaesthesiologica Scandinavica, 52, 987-990. doi:10.1111/j.1399-6576.2008.01649.x [21] Den Oudsten, B.L., Van Heck, G.L., Van der Steeg, A.F.W., Roukema, J.A. and De Vries, J. (2009) Predictors of depressive symptoms 12 months after surgical treatment of early-stage breast cancer. Psycho-Oncology, 18, 1230-1237. doi:10.1002/pon.1518 [22] Li, X.-M., Zhou, K.-N., Yan, H., Wang, D.-L. and Zhang, Y.-P. (2012) Effects of music therapy on anxiety of patients with breast cancer after radical mastectomy: A randomized clinical trial. Journal of Advanced Nursing, 68, 1145-1155. doi:10.1111/j.1365-2648.2011.05824.x [23] Nater, U.M., Rohleder, N., Schlotz, W., Ehlert, U. and Kirschbaum, C. (2007) Determinants of the diurnal course of salivary alpha-amylase. Psychoneuroendocrinology, 32, 392-401. doi:10.1016/j.psyneuen.2007.02.007 [24] Yamaguchi, M., Kanemori, T., Kanemaru, M., Takai, N., Mizuno, Y. and Yoshida, H. (2004) Performance evaluation of salivary amylase activity monitor. Biosensors & Bioelectronics, 20, 491-497. doi:10.1016/j.bios.2004.02.012 [25] Yamaguchi, M., Deguchi, M., Wakasugi, J., Ono, S., Takai, N., Higashi, T. and Mizuno, Y. (2006) Hand-held monitor of sympathetic nervous system using salivary amylase activity and its validation by driver fatigue assessment. Biosensors & Bioelectronics, 21, 1007-1014. doi:10.1016/j.bios.2005.03.014 [26] Shetty, V., Zigler, C., Robles, T.F., Elashoff, D. and Yamaguchi, M. (2011) Developmental validation of a point-of-care, salivary α-amylase biosensor. Psychoneuroendocrinology, 36, 193-199. doi:10.1016/j.psyneuen.2010.07.008 [27] Spielberger, C.D., Gorsuch, R.L., Lushene, P.R., Vagg, P.R. and Jacobs, G.A. (1983) Manual for the state-trait anxiety inventory (form Y) (“self-evaluation questionnaire”). Consulting Psychologists Press Inc., Palo Alto. [28] Hidano, T., Fukuhara, M., Iwawaki, S., Soga, S. and Spielberger, C.D. (2000) New STAI manual for the state-trait anxiety inventory-form JYZ. Jitsumu Kyouiku Press Inc., Tokyo. [29] Kelly, A.-M. (1998) Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain? Academic Emergency Medicine, 5, 1086-1090. doi:10.1111/j.1553-2712.1998.tb02667.x [30] Bijur, P.E., Silver, W. and Gallagher, E.J. (2001) Reliability of the visual analog scale for measurement of acute pain. Academic Emergency Medicine, 8, 1153-1157. doi:10.1111/j.1553-2712.2001.tb01132.x [31] Rohleder, N., Nater, U.M., Wolf, J.M., Ehlert, U. and Kirschbaum, C. (2004) Psychosocial stress-induced activation of salivary alpha-amylase: An indicator of sympathetic activity? Annals of the New York Academy of Sciences, 1032, 258-263. doi:10.1196/annals.1314.033 [32] Akselrod, S., Gordon, D., Ubel, F.A., Shannon, D.C., Berger, A.C. and Cohen, R.J. (1981) Power spectrum analysis of heart rate fluctuation: A quantitative probe of beat-to-beat cardiovascular control. Science, 213, 220-222. doi:10.1126/science.6166045 [33] Arai, Y.-C.P., Matsubara, T., Shimo, K., Osuga, T., Shida, T., Suzuki, C., Ohta, A., Tohyama, Y., Nishida, K. and Arakawa, M. (2009) Small correlation between salivary α-amylase activity and intensity in patients with cancer pain. Acta Anaesthesiologica Scandinavica, 53, 408. doi:10.1111/j.1399-6576.2008.01833.x [34] Campos, M.J., Raposo, N.R., Ferreira, A.P. and Vitral, R.W. (2011) Salivary α-amylase activity: A possible indicator of pain-induced stress in orthodontic patients. Pain Medicine, 12, 1162-1166. doi:10.1111/j.1526-4637.2011.01185.x [35] Milad, M.P., Klock, S.C., Moses, S. and Chatterton, R. (1998) Stress and anxiety do not result in pregnancy wastage. Human Reproduction, 13, 2296-2300. doi:10.1093/humrep/13.8.2296 [36] Amar, D., Fleisher, M., Pantuck, C.B., Shamoon, H., Zhang, H., Roistacher, N., Leung, D.H.Y., Ginsburg, I. and Smiley, R.M. (1998) Persistent alterations of the autonomic nervous system after noncardiac surgery. Anesthesiology, 89, 30-42. doi:10.1097/00000542-199807000-00008 [37] Marsch, S.C.U., Skarvan, K., Schaefer, H.-G., Naegeli, B., Paganoni, R., Castelli, I. and Scheidegger, D. (1994) Prolonged decrease in heart rate variability after elective hip arthoplasty. British Journal of Anaesthesia, 72, 643-649. doi:10.1093/bja/72.6.643 [38] Ushiyama, T., Mizushige, K., Wakabayashi, H., Nakatsu, T., Ishimura, K., Tsuboi, Y., Maeta, H. and Suzuki, Y. (2008) Analysis of heart rate variability as an index of noncardiac surgical stress. Heart and Vessels, 23, 53-59. doi:10.1007/s00380-007-0997-6 [39] Ledowski, T., Reimer, M., Chavez, V., Kapoor, V. and Wenk, M. (2012) Effects of acute postoperative pain on catecholamine plasma levels, hemodynamic parameters, and cardiac autonomic control. Pain, 153, 759-764. doi:10.1016/j.pain.2011.11.002 [40] Kang, Y. (2010) Psychological stress-induced changes in salivary α-amylase and adrenergic activity. Nursing & Health Sciences, 12, 477-484. doi:10.1111/j.1442-2018.2010.00562.x [41] Ledowski, T., Ang, B., Schmarbeck, T. and Rhodes, J. (2009) Monitoring of sympathetic tone to assess postoperative pain: Skin conductance vs surgical stress index. Anaesthesia, 64, 727-731. doi:10.1111/j.1365-2044.2008.05834.x [42] Rohleder, N., Wolf, J.M., Maldonando, E.F. and Kirschbaum, C. (2006) The psychosocial stress-induced increase in salivary alpha-amylase is independent of saliva flow rate. Psychophysiology, 43, 645-652. doi:10.111/j.1469-8986.2006.00457.x [43] Bosch, J.A., Veerman, E.C.I., De Geus, E.J. and Proctor, G.B. (2011) α-Amylase as a reliable and convenient measure of sympathetic activity: Don’t start salivating just yet! Psychoneuroendocrinology, 36, 449-453. doi:10.1016/j.psyneuen.2010.12.019
[1] Leinonen, T. and Leino-Kilpi, H. (1999) Research in peri-operative nursing care. Journal of Clinical Nursing, 8, 123-138. doi:10.1046/j.1365-2702.1999.00239.x [2] Johansson, K., Nuutila, L., Virtanen, H., Katajisto, J. and Salanter?, S. (2005) Preoperative education for orthopaedic patients: Systematic review. Journal of Advanced Nursing, 50, 212-223. doi:10.1111/j.1365-2648.2005.03381.x [3] Roykulcharoen, V. and Good, M. (2004) Systematic relaxation to relieve postoperative pain. Journal of Advanced Nursing, 48, 140-148. doi:10.1111/j.1365-2648.2004.03181.x [4] Seers, K. and Carroll, D. (1998) Relaxation techniques for acute pain management: A systematic review. Journal of Advanced Nursing, 27, 466-475. doi:10.1046/j.1365-2648.1998.00538.x [5] Montgomery, G.H., Bovbjerg, D.H., Schnur, J.B., David, D., Goldfarb, A., Weltz, C.R., Schechter, C., Graff-Zivin, J., Tatrow, K., Price, D.D. and Silverstein, J.H. (2007) A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients. Journal of the National Cancer Institute, 99, 1304-1312. doi:10.1093/jnci/djm106 [6] Bauer, B.A., Cutshall, S.M., Wentworth, L.J., Engen, D., Messner, P.K., Wood, C.M., Brekke, K.M., Kelly, R.F. and Sundt, T.M. (2010) Effect of massage therapy on pain, anxiety, and tension after cardiac surgery: A randomized study. Complementary Therapies in Clinical Practice, 16, 70-75. doi:10.1016/j.ctcp.2009.06.012 [7] Yamaguchi, M., Kanemaru, M., Kanemori, T. and Mizuno, Y. (2003) Flow-injection-type biosensor system for salivary amylase activity. Biosensors & Bioelectronics, 18, 835-840. doi:10.1016/S0956-5663(03)00007-1 [8] Benson, H. and Klipper, M.Z. (2001) The relaxation response. Harper Collins Publishers Inc., New York. [9] Nater, U.M. and Rohleder, N. (2009) Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: Current state of research. Psychoneuroendocrinology, 34, 486-496. doi:10.1016/j.psyneuen.2009.01.014 [10] Proctor, G.B. and Carpenter, G.H. (2007) Regulation of salivary gland function by autonomic nerves. Autonomic Neuroscience, 133, 3-18. doi:10.1016/j.autneu.2006.10.006 [11] Chatterton, R.T. Jr., Vogelsong, K.M., Lu, Y.C. and Hudgens, G.A. (1997) Hormonal responses to psychological stress in men preparing for skydiving. The Journal of Clinical Endocrinology and Metabolism, 82, 2503-2509. doi:10.1210/jc.82.8.2503 [12] Bosch, J.A., De Geus, E.J.C., Veerman, E.C.I., Hoogstraten, J. and Amerongen, A.V.N. (2003) Innate secretory immunity in response to laboratory stressors that evoke distinct patterns of cardiac autonomic activity. Psychosomatic Medicine, 65, 245-258 doi:10.1097/01.PSY.0000058376.50240.2D [13] Skosnik, P.D., Chatterton, R.T. Jr., Swisher, T. and Park, S. (2000) Modulation of attentional inhibition by norepinephrine and cortisol after psychological stress. International Journal of Psychophysiology, 36, 59-68. doi:10.1016/S0167-8760(99)00100-2 [14] Morrison, W.E., Haas, E.C., Shaffner, D.H., Garrett, E.S. and Fackler, J.C. (2003) Noise, stress, and annoyance in a pediatric intensive care unit. Critical Care Medicine, 31, 113-119. doi:10.1097/00003246-200301000-00018 [15] Nater, U.M., Rohleder, N., Gaab, J., Bergera, S., Juda, A., Kirschbaum, C. and Ehlert, U. (2005) Human salivary α-amylase reactivity in a psychosocial stress paradigm. International Journal of Psychophysiology, 55, 333-342. doi:10.1016/j.ijpsycho.2004.09.009 [16] Noto, Y., Sato, T., Kudo, M., Kurata, K. and Hirota, K. (2005) The relationship between salivary biomarkers and state-trait anxiety inventory score under mental arithmetic stress: A pilot study. Anesthesia and Analgesia, 101, 1873-1876.doi:10.1213/01.ANE.0000184196.60838.8D [17] Takai, N., Yamaguchi, Y., Aragakia, T., Eto, K., Uchihashia, K. and Nishikawa, Y. (2004) Effect of psychological stress on the salivary cortisol and amylase levels in healthy young adults. Archives of Oral Biology, 49, 963-968. doi:10.1016/j.archoralbio.2004.06.007 [18] Shirasaki, S., Fujii, H., Takahashi, M., Sato, T., Ebina, M., Noto, Y. and Hirota, K. (2007) Correlation between salivary α-amylase activity and pain scale in patients with chronic pain. Regional Anesthesia and Pain Medicine, 32, 120-123. doi:10.1016/j.rapm.2006.11.008 [19] Hodgson, N.A. and Andersen, S. (2008) The clinical efficacy of reflexology in nursing home residents with dementia. Journal of Alternative and Complementary Medicine, 14, 269-275. doi:10.1089/acm.2007.0577 [20] Arai, Y.-C.P., Sakakibara, S., Ito A., Ohshima, K., Sakakibara, T., Nishi, T., Hibino, S., Niwa, S. and Kuniyoshi, K. (2008) Intra-operative natural sound decreases salivary amylase activity of patients undergoing inguinal hernia repair under epidural anesthesia. Acta Anaesthesiologica Scandinavica, 52, 987-990. doi:10.1111/j.1399-6576.2008.01649.x [21] Den Oudsten, B.L., Van Heck, G.L., Van der Steeg, A.F.W., Roukema, J.A. and De Vries, J. (2009) Predictors of depressive symptoms 12 months after surgical treatment of early-stage breast cancer. Psycho-Oncology, 18, 1230-1237. doi:10.1002/pon.1518 [22] Li, X.-M., Zhou, K.-N., Yan, H., Wang, D.-L. and Zhang, Y.-P. (2012) Effects of music therapy on anxiety of patients with breast cancer after radical mastectomy: A randomized clinical trial. Journal of Advanced Nursing, 68, 1145-1155. doi:10.1111/j.1365-2648.2011.05824.x [23] Nater, U.M., Rohleder, N., Schlotz, W., Ehlert, U. and Kirschbaum, C. (2007) Determinants of the diurnal course of salivary alpha-amylase. Psychoneuroendocrinology, 32, 392-401. doi:10.1016/j.psyneuen.2007.02.007 [24] Yamaguchi, M., Kanemori, T., Kanemaru, M., Takai, N., Mizuno, Y. and Yoshida, H. (2004) Performance evaluation of salivary amylase activity monitor. Biosensors & Bioelectronics, 20, 491-497. doi:10.1016/j.bios.2004.02.012 [25] Yamaguchi, M., Deguchi, M., Wakasugi, J., Ono, S., Takai, N., Higashi, T. and Mizuno, Y. (2006) Hand-held monitor of sympathetic nervous system using salivary amylase activity and its validation by driver fatigue assessment. Biosensors & Bioelectronics, 21, 1007-1014. doi:10.1016/j.bios.2005.03.014 [26] Shetty, V., Zigler, C., Robles, T.F., Elashoff, D. and Yamaguchi, M. (2011) Developmental validation of a point-of-care, salivary α-amylase biosensor. Psychoneuroendocrinology, 36, 193-199. doi:10.1016/j.psyneuen.2010.07.008 [27] Spielberger, C.D., Gorsuch, R.L., Lushene, P.R., Vagg, P.R. and Jacobs, G.A. (1983) Manual for the state-trait anxiety inventory (form Y) (“self-evaluation questionnaire”). Consulting Psychologists Press Inc., Palo Alto. [28] Hidano, T., Fukuhara, M., Iwawaki, S., Soga, S. and Spielberger, C.D. (2000) New STAI manual for the state-trait anxiety inventory-form JYZ. Jitsumu Kyouiku Press Inc., Tokyo. [29] Kelly, A.-M. (1998) Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain? Academic Emergency Medicine, 5, 1086-1090. doi:10.1111/j.1553-2712.1998.tb02667.x [30] Bijur, P.E., Silver, W. and Gallagher, E.J. (2001) Reliability of the visual analog scale for measurement of acute pain. Academic Emergency Medicine, 8, 1153-1157. doi:10.1111/j.1553-2712.2001.tb01132.x [31] Rohleder, N., Nater, U.M., Wolf, J.M., Ehlert, U. and Kirschbaum, C. (2004) Psychosocial stress-induced activation of salivary alpha-amylase: An indicator of sympathetic activity? Annals of the New York Academy of Sciences, 1032, 258-263. doi:10.1196/annals.1314.033 [32] Akselrod, S., Gordon, D., Ubel, F.A., Shannon, D.C., Berger, A.C. and Cohen, R.J. (1981) Power spectrum analysis of heart rate fluctuation: A quantitative probe of beat-to-beat cardiovascular control. Science, 213, 220-222. doi:10.1126/science.6166045 [33] Arai, Y.-C.P., Matsubara, T., Shimo, K., Osuga, T., Shida, T., Suzuki, C., Ohta, A., Tohyama, Y., Nishida, K. and Arakawa, M. (2009) Small correlation between salivary α-amylase activity and intensity in patients with cancer pain. Acta Anaesthesiologica Scandinavica, 53, 408. doi:10.1111/j.1399-6576.2008.01833.x [34] Campos, M.J., Raposo, N.R., Ferreira, A.P. and Vitral, R.W. (2011) Salivary α-amylase activity: A possible indicator of pain-induced stress in orthodontic patients. Pain Medicine, 12, 1162-1166. doi:10.1111/j.1526-4637.2011.01185.x [35] Milad, M.P., Klock, S.C., Moses, S. and Chatterton, R. (1998) Stress and anxiety do not result in pregnancy wastage. Human Reproduction, 13, 2296-2300. doi:10.1093/humrep/13.8.2296 [36] Amar, D., Fleisher, M., Pantuck, C.B., Shamoon, H., Zhang, H., Roistacher, N., Leung, D.H.Y., Ginsburg, I. and Smiley, R.M. (1998) Persistent alterations of the autonomic nervous system after noncardiac surgery. Anesthesiology, 89, 30-42. doi:10.1097/00000542-199807000-00008 [37] Marsch, S.C.U., Skarvan, K., Schaefer, H.-G., Naegeli, B., Paganoni, R., Castelli, I. and Scheidegger, D. (1994) Prolonged decrease in heart rate variability after elective hip arthoplasty. British Journal of Anaesthesia, 72, 643-649. doi:10.1093/bja/72.6.643 [38] Ushiyama, T., Mizushige, K., Wakabayashi, H., Nakatsu, T., Ishimura, K., Tsuboi, Y., Maeta, H. and Suzuki, Y. (2008) Analysis of heart rate variability as an index of noncardiac surgical stress. Heart and Vessels, 23, 53-59. doi:10.1007/s00380-007-0997-6 [39] Ledowski, T., Reimer, M., Chavez, V., Kapoor, V. and Wenk, M. (2012) Effects of acute postoperative pain on catecholamine plasma levels, hemodynamic parameters, and cardiac autonomic control. Pain, 153, 759-764. doi:10.1016/j.pain.2011.11.002 [40] Kang, Y. (2010) Psychological stress-induced changes in salivary α-amylase and adrenergic activity. Nursing & Health Sciences, 12, 477-484. doi:10.1111/j.1442-2018.2010.00562.x [41] Ledowski, T., Ang, B., Schmarbeck, T. and Rhodes, J. (2009) Monitoring of sympathetic tone to assess postoperative pain: Skin conductance vs surgical stress index. Anaesthesia, 64, 727-731. doi:10.1111/j.1365-2044.2008.05834.x [42] Rohleder, N., Wolf, J.M., Maldonando, E.F. and Kirschbaum, C. (2006) The psychosocial stress-induced increase in salivary alpha-amylase is independent of saliva flow rate. Psychophysiology, 43, 645-652. doi:10.111/j.1469-8986.2006.00457.x [43] Bosch, J.A., Veerman, E.C.I., De Geus, E.J. and Proctor, G.B. (2011) α-Amylase as a reliable and convenient measure of sympathetic activity: Don’t start salivating just yet! Psychoneuroendocrinology, 36, 449-453. doi:10.1016/j.psyneuen.2010.12.019