臺灣博碩士論文加值系統

研究目的：早在許多年前中國人已會使用針灸來治療一些胃腸道不適之症狀，然而關於針灸治療胃腸功能性異常疾病相關之作用機轉頗為復雜，針灸治療所產生的效果與治療的對象、所使用的穴位、運針之手法、以及當時胃腸功能性異常之狀況等等條件有關。以往的研究發現使用電針刺激足三里穴位，可以增強健康受試者胃肌電波規律之程度，然而其詳細之作用機轉仍然不甚清楚，ㄧ般推論自律神經系統在其中可能扮演重要之角色。本研究首先利用心率變異分析記錄，探討針灸對健康受試者自律神經功能的影響，接者進一步同時記錄心率變異分析以及血液中與腸道相關之賀爾蒙，在進食之後所產生之變化，來比較分析腹部迷走神經系統與心臟迷走神經系統反應在進食後表現之模式是否相同。
研究方法及資料：第一部分的研究中，利用兩種不同之電針頻率（2 Hz及100Hz）分別刺激足三里以及手三里穴位，並與非穴位之對照組比較，分析15位健康受試者在5種不同條件下，應用功率頻譜分析心率變異數來研究分析自律神經系統功能的變化，其中低頻功率的大小可視為交感神經系統功能變化的指標，高頻功率的大小可視為副交感神經系統功能變化的指標，而低高頻功率比則可用以評估交感與副交感神經變化的調控狀況；接者在第二部分的研究中，利用同時記錄心率變異分析以及血液中4種與腸道自律神經功能相關之賀爾蒙，在空腹時以及在進食之後每20分鐘紀錄一次，總共記錄120分鐘， ㄧ共22位分析健康受試者在進食之後所產生之變化，來比較分析腹部迷走神經系統功能變化與心臟迷走神經系統功能反應在進食後之表現是否同步。
研究結果：在第一部分的研究中，以2 Hz頻率電針刺激足三里穴位，在針灸後之時段呈現低高頻功率比增加（表示較高之交感神經活動），然而這種變化並未達統計學差異之水準，然而在其他條件下低頻功率的大小及高頻功率的大小，在針灸後並沒有顯著之變化。在第二部分的研究中，心跳之速率在進食後顯著的增加，高頻功率（副交感神經功能的指標）在進食後40至120分鐘顯著的減少；而且低頻功率（交感神經功能的指標）在進食後60至120分鐘也呈現顯著的減少，然而低高頻功率比（表示較高之交感神經活動）在進食後20至120分鐘顯著的增加；4種與腸道自律神經功能相關之賀爾蒙，只有pancreatic polypeptide在進食後20分鐘呈現2倍以上之增加，隨後在的120分鐘當中也持續有顯著的增加。
結論與建議：以2 Hz及100Hz電針頻率刺激足三里以及手三里穴位，並不會產生顯著的心率變異變化，顯示刺激這兩個穴位對心臟迷走神經影響不顯著；而進食後高頻功率（副交感神經功能的指標）、低頻功率（交感神經功能的指標）以及低高頻功率比（表示較高之交感神經活動）之變化與腸道賀爾蒙pancreatic polypeptide在進食後之變化模式也有顯著的不同，因此推論雖然都是由迷走神經所支配，但在進食後之後，腹部迷走神經與心臟迷走神經反應在進食後之表現模式並不一致；所以當臨床上使用心率變異分析來探究各種狀況下，心臟迷走神經反應與各種疾病或治療方法的效果時，心率變異分析應該是一種非侵入性且便利之評估的方法；然而要想同時探究腹部迷走神經反應與各種疾病或治療方法的效果時，需要同時測量與腸道自律神經功能相關之賀爾蒙（如pancreatic polypeptide），才能夠真實的反應腹部迷走神經反應之變化。

Objective: Acupuncture has been used to treat gastrointestinal symptoms in oriental countries for many years. The impact of acupuncture on gastrointestinal function is complex, and results depend upon the species studied, the acu-points employed, the methods of manipulation, and the underlying functional activity of the gut. Electrical stimulation of St. 36 (Zusanli) has been shown to enhance the regularity of gastric myoelectrical activity in healthy subjects. However, the underlying mechanism by which acupuncture alters gastric myoelectrical activity is still not clear. To elucidate the possible role of the autonomic nervous system in mediating the effect of acupuncture, we monitored heart rate variability (HRV), a widely used index of vagal discharge at the sinoatrial node of the heart before, during and after electroacupuncture. Furthermore, several studies have supported the hypothesis of different presentations in the autonomic nervous system (ANS) between cardiac and gastric vagal activity. Due to the regionality of the ANS, different responses among different organ systems to the same stimulation (such as a meal) are quite possible.
Methods and Materials: In the first study, we applied two different frequencies (2 Hz and 100 Hz) of electrical stimulation at St. 36 (Zusanli) and LI. 10 (Shousanli) in 15 healthy volunteers. Low frequency (LF, sympathetic activity), high frequency (HF, vagal activity) and LF/HF ratio (sympathovagal balance) derived from the HRV were analyzed and compared at the two different frequencies. In the subsequent study, we monitored the postprandial changes of heart rate variability (HRV) and GI hormones to determine whether both responded in a similar pattern. Twenty-two healthy volunteers (6 males and 16 females) were enrolled. After recording a baseline ECG rhythm, further recordings were made at 20 minute intervals for 120 minutes after a test meal. Serum human pancreatic polypeptide (PP), leptin, and total and active ghrelin levels were measured. Results: The results of the first study showed an increase in the LF/HF ratio (indicating greater sympathetic activity) during the post-acupuncture period using 2 Hz of electrical stimulation at St. 36 (Zusanli). However, the overall change was not statistically significant. In addition, the power of LF and HF did not change significantly with electroacupuncture at St. 36 (Zusanli) and LI. 10 (Shousanli). In the subsequent study, after the meal, HR increased significantly from baseline at each time point, except for 20 minutes after the meal. The high frequency (HF) power decreased significantly from 40 minutes to 120 minutes after the meal. In addition, the low frequency (LF) power also decreased significantly from 60 minutes to 120 minutes. However, the LF/HF ratio increased significantly from 20 minutes to 120 minutes. There was a marked increase (> 2 fold) of PP at 20 minutes after the meal, and the increase was sustained throughout the test period. Conclusion and Suggestion: In conclusion, applying 2 Hz or 100Hz electroacupuncture at St. 36 (Zusanli) or LI. 10 (Shousanli) did not affect cardiovagal activity in normal volunteers. This phenomenon might be due to a difference in presentation in the autonomic nervous system between cardiac and abdominal vagal activity. In addition, the results of the subsequent study suggested that HRV reflects cardiac, but not equivalently, abdominovagal activity. Therefore, HRV as an abdominovagal activity measurement in patients with GI functional problems should be used with caution, and other markers such as PP should be included.

Contents
Literature Review---------------------------------- 1
Purposes-------------------------------------------21
PART 1
Effect of electroacupuncture on St. 36 (Zusanli) and LI. 10 (Shousanli) acupuncture points on autonomic nervous system measured by heart rate variability
Abstract----------------------------------24
Introduction------------------------------26
Methods-----------------------------------28
Results-----------------------------------32
Discussion--------------------------------34
References--------------------------------39
Tables------------------------------------43
Figures-----------------------------------45
PART 2
Varying postprandial response in abdominovagal and cardiovagal activity among normal subjects by comparing gut hormones with heart rate variability

Abstract----------------------------------50
Introduction------------------------------52
Methods-----------------------------------54 Results-----------------------------------58
Discussion--------------------------------60
References--------------------------------66 Tables------------------------------------71
Figures-----------------------------------74
Conclusions----------------------------------------75

part 1
1. Nasir LS. Acupuncture. Prim Care Clin Office Pract 2002; 29: 393-405.
2. Diehl DL, Kaplan G, Coulter I, et al. Use of acupuncture by American physicians. J Altern Complement Med 1997; 3: 119-126.
3. Napadow V, Makris N, Liu J, et al. Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI. Hum Brain Mapp 2005; 24: 193-205.
4. Pomeranz B, Stux G (eds). Scientific Bases of Acupuncture. New York: Springer-Verlag, 1989.
5. Hsieh JC, Tu CH, Chen FP, et al. Activation of the hypothalamus characterizes the acupuncture stimulation at the analgesic point in human: a positron emission tomography study. Neurosci Lett 2001; 307: 105-108.
6. Wu MT, Sheen JM, Chuang KH, et al. Neuronal specificity of acupuncture response: an fMRI study with electroacupuncture. Neuroimage 2002; 16: 1028-1037.
7. Fang JL, Krings T, Weidemann J, et al. Functional MRI in healthy subjects during acupuncture: different effects of needle rotation in real and false acupoints. Neuroradiology 2004; 46: 359-362.
8. Audette JF, Ryan AH. The role of acupuncture in pain management. Phys Med Rehabil Clin N Am 2004; 15: 749-772.
9. Zhang RX, Lao L, Wang L, et al. Involvement of opioid receptors in electroacupuncture-produced anti-hyperalgesia in rats with peripheral inflammation. Brain Res 2004; 1020: 12-17.
10. Zhang RX, Lao L, Wang X, et al. Electroacupuncture combined with indomethacin enhances antihyperalgesia in inflammatory rats. Pharmacol Biochem Behav 2004; 78: 793-797.
11. Cho ZH, Chung SC, Jones JP, et al. New findings of the correlation between acupoints and corresponding brain cortices using functional MRI. Proc Natl Acad Sci U S A 1998; 95: 2670-2673.
12. Liu WC, Feldman SC, Cook DB, et al. fMRI study of acupuncture-induced periaqueductal gray activity in humans. Neuroreport 2004; 15: 1937-1940.
13. Siedentopf C, Golaszewski S, Haala I, et al. Die funktionelle Magnetresonanz-Tomographie in der Akupunkturforschung. Dtsch Z Akup 2004; 47: 6-13.
14. Yan B, Li K, Xu J, et al. Acupoint-specific fMRI patterns in human brain. Neurosci Lett 2005; 383: 236-240.
15. Siedentopf CM, Koppelstaetter F, Haala A, et al. Laser acupuncture induced specific cerebral corticol and subcorticol activations in humans. Lasers Med Sci 2005; 20: 68-73.
16. Han J S. Acupuncture and endorphins. Neurosci Lett 2004; 361: 258–61.
17. Sung HJ, Kim YS, Kim IS, et al. Proteomic analysis of differential protein expression in neuropathic pain and electroacupuncture treatment models. Proteomics 2004; 4: 2805-2813.
18. Liu XY, Zhou HF, Pan YL, et al. Electro-acupuncture stimulation protects dopaminergic neurons from inflammation-mediated damage in medial forebrain bundle-transected rats. Exp Neurol 2004; 189: 189-196.
19. Park HJ, Lim S, Joo WS, et al. Acupuncture prevents 6-hydroxydopamine-induced neuronal death in the nigrostratial dopaminergic system in the rat Parkinson’s disease model. Exp Neurol 2003; 180: 92-97.
20. Essentials of Chinese acupuncture. Compiled by Beijing College of Traditional Chinese Medicine. Beijing, China: Foreign Languages Press, 1980:5-8.
21. Dundee JW, Chestnutt WN, Ghaly RG, et al. Traditional Chinese acupuncture: A potential useful antiemetic? Br Med J 1986; 293: 583-584.
22. Dundee JW, Ghaly RG, Fitzpatrick KTJ, et al. Acupuncture to prevent cisplatin-associated vomiting. Lancet 1987; 1:1083.
23. Hu S, Stern RM, Koch KL. Electrical acustimulation relives vection-induced motion sickness. Gastroenterology 1992; 102:1854-1858.
24. Lin X, Liang J, Ren J, et al. Electrical stimulation of acupuncture points enhances gastric myoelectrical activity in humans. Am J Gastroenterol 1997; 92:1527-1530.
25. Chou JW, Chang YH, Chang CS, et al. The effect of different frequency electrical acu-stimulation on gastric myoelectrical activity in healthy subjects. Hepatogastroenterology 2003; 50:582-586.
26. Chang CS, Chou JW, Ko CW, et al. Cutaneous electrical stimulation of acupuncture points may enhance gastric myoelectrical regularity. Digestion 2002; 66: 106-111.
27. Chang CS, Ko CW, Wu CY, et al. The effect of electrical stimulation on acupuncture points on diabetic patients with gastric dysrhythmia—a pilot study. Digestion 2001: 64: 184-190.
28. Hayano J, Sakakibara Y, Yamada A. Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am J Cardiol 1991; 67: 199-204.
29. Malliani A, Pagani M, Lombardi F, et al. Cardiovascular neural regulation explored in the frequency domain. Circulation tion 1997; 96(9): 3224-3232.
30. Dekker JM, Crow RS, Folsom AR, et al. Low heart rate variability in a 2-min rhythm strip predicts risk of coronary heart disease and mortality from several causes. The ARIC Study. Circulation 2000; 102: 1239-1244.
31. Liao D, Cai J, Rosamond WD, et al. Cardiac autonomic function and incident coronary heart disease. A population-based case-cohort study: The ARIC study. Am J Epidemiol 1997; 145(8): 696-706.
32. Hon EH, Lee ST. Electronic evaluation of the foetal heart rate patterns preceding foetal death. Am J Obstet Gynecol 1963; 87: 814-826.
33. Wolf MM, Varigos GA, Hunt D, et al. Sinus arrhythmia in acute myocardial infarction. Med J Aust 1978; 2: 52-53.
34. Whitsel EA, Raghunathan TE, Pearce RM, et al. RR-interval variation, the QT interval index and risk of primary cardiac arrest among patients without clinically recognised heart disease. Eur Heart J 2001; 22: 165-173.
35. Ewing DJ, Campbell IW, Clarke BF. The natural history of diabetic autonomic neuropathy. Q J Med 1980; 193: 95-108.
36. O’Brien IA, McFadden JP, Corrall RJM. The influence of autonomic neuropathy on mortality in insulin-dependent diabetes. Q J Med 1991; 79: 495-502.
37. Taylor JA, Carr DL, Myers CW, et al. Mechanisms underly- ing very-low-frequency RR-interval oscillations in humans. Circula tion 1998; 98(6): 547-555.
38. American Diabetes Association, Diabetic neuropathy, Clinical practice recommendations 1996. Diabetes Care 1996; 19(Suppl 1): S67-S92.
39. Ziegler D. Cardiovascular autonomic neuropathy: clinical mani festations and measurement. Diabetes Rev 1999; 7(4): 342-357.
40. Poulsen PL, Ebbehoj E, Hansen KW, et al. 24-h blood pressure and autonomic function is related to albumin excretion within the normoalbuminuric range in IDDM patients. Diabetologia 1997; 40: 718-725.
41. Stamler J, Vaccato O, Neaton J, et al. Diabetes, other risk factors, and the 12-year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993; 16: 434-444.
42. Chang CH, Huang JL, Ting CT, et al. Atropine-induced HRV alteration is not amended by electroacupuncture on Zusanli. Am Chin Med 2005; 33: 307-314.
43. Malliani A, Pagani M, Lombardi F, et al. Cardiovascular neural regulation explored in the frequency domain. Circulation 1991; 84: 482-492.
44. Ori Z, Monir G, Weiss J, et al. Heart rate variability. Frequency domain analysis. Cardiology Clinics 1992; 10: 499-537.
45. Pagan M, Lombardi F, Guzzetti S, et al. A power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympathovagal interaction in man and conscious dogs. Circulation Research 1986; 59: 178-193.
46. Nishijo K, Mori H, Yosikawa K, et al. Decreased heart rate by acupuncture stimulation in humans via facilitation of cardiac vagal activity and suppression of cardiac sympathetic nerve. Neuroscience Letters 1997; 227: 165-168.
47. Chang S, Chao WL, Chiang MJ, et al. Effects of acupuncture at Neiguan (PC 6) of the pericardial meridian on blood pressure and heart rate variability. Chin J Physiol 2008; 51: 167-177.
48. Huang ST, Chen GY, Lo HM, et al. Increase in the vagal modulation by acupuncture at neiguan point in the healthy subjects. Am J Chin Med 2005; 33:157-164.
49. Ouyang H, Yin J, Wang Z, et al. Electroacupuncture accelerates gastric emptying in association with changes in vagal activity. Am J Physiol Gastrointest Liver Physiol 2002; 282: G390-G396.
50. Lucini D, Cerchiello M, Basilisco G, et al. Autonomic control of heart period in duodenal ulcer patients: insights from spectral analysis of heart rate variability. Auton Neurosci 2000; 84: 122–129.
51. Tougas G, Spaziani R, Hollerbach S, et al. Cardiac autonomic function and oesophageal acid sensitivity in patients with non-cardiac chest pain. Gut 2001; 49: 706-712.
52. Lorena SL, Figueiredo MJ, Almeida JR, et al. Autonomic function in patients with functional dyspepsia assessed by 24-hour heart rate variability. Dig Dis Sci 2002; 47: 27-31.
53. Murray CD, Flynn J, Ratcliffe L, Jet al. Effects of acute physical and psychological stress and its influence on autonomic outflow to the gut in irritable bowel syndrome. Gastroenterology 2004; 127: 1695-1703.
54. Buysschaert M, Donckier J, Dive A, et al. Gastric acid and pancreatic polypeptide responses to sham feeding are impaired in diabetic subjects with autonomic neuropathy. Diabetes 1985; 34: 1181-1185.
55. Ziegler D, Schadewaldt P, Pour Mirza A, et al. [13C]Octanoic acid breath test for non-invasive assessment of gastric emptying in diabetic patients; validation and relationship to gastric symptoms and cardiovascular autonomic function. Diabetologia 1996; 39: 823-830.
56. Hjelland I, Oveland NP, Leversen K, et al. Insulin-induced hypoglycemia stimulates gastric vagal activity and motor function without increasing cardiac vagal activity. Digestion 2005; 72: 43-48.
57. Kimmel JR, Pollock HG, Hazelwood RL. Isolation and characterization of chicken insulin. Endocrinology 1968; 83: 1323.
58. Schwartz TW. Pancreatic polypeptide: A hormone under vagal control. Gastroenterology 1983; 85: 1411-1425.
59. Guzman S, Lonovics J, Devitt PG, et al. Hormone-stimulated release of pancreatic polypeptide before and after vagotomy in dogs. Am J Physiol 1981; 240: G114-121.
60. Schwartz TW, Stenquist B, Olbe L, et al. Synchronous oscillations in the basal secretion of pancreatic-polypeptide and gastric acid. Depression by cholinergic blockade of pancreatic-polypeptide concentrations in plasma. Gastroenterology 1979; 76: 14-19.
61. Greydanus MP, Vassallo M, Camilleri M, et al. Neurohormonal factors in functional dyspepsia: insights on pathophysiological mechanisms. Gastroenterology 1991; 100: 1313-1318.
62. Konturek SJ, Bielanski W, Solomon TE. Effects of antral mucosectomy, L-346, 718 and atropine on cephalic phase of gastric and pancreatic secretion in dogs. Gastroenterology 1990; 98: 47-55.
63. Liu S, Peng S, Hou X, et al. Transcutaneous electroacupuncture improves dyspeptic symptoms and increases high frequency heart rate variability in patients with functional dyspepsia. Neurogastroenterol Motil 2008; 20: 1204-1211.
64. Chen J, Song GQ, Yin J, et al. Electroacupuncture improves impaired gastric motility and slow waves induced by rectal distension in dogs. Am J Physiol Gastrointest Liver Physiol 2008; 295: G614-G620.

part2
1. Merio R, Festa A, Bergmann H, et al. Slow gastric emptying in type 1 diabetes: relation to autonomic and peripheral neuropathy, blood glucose and glycemic control. Diabetes Care 1997; 20: 419-423.
2. Kamath MV, Spaziani R, Ullal S, et al. The effect of sham feeding on neurocardiac regulation in healthy human volunteers. Can J Gastroenterol 2007; 21: 721-726.
3. Ori Z, Monir G, Weiss J, et al. Heart rate variability: Frequency domain analysis. Cardiol Clin 1992; 10: 499-537.
4. Pagani M, Lombardi F, Guzzetti S, et al. A power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympathovagal interaction in man and conscious dogs. Cir Res 1986; 59: 178-193.
5. Lucini D, Cerchiello M, Basilisco G, et al. Autonomic control of heart period in duodenal ulcer patients: insights from spectral analysis of heart rate variability. Auton Neurosci 2000; 84: 122-129.
6. Tougas G, Spaziani R, Hollerbach S, et al. Cardiac autonomic function and oesophageal acid sensitivity in patients with non-cardiac chest pain. Gut 2001; 49: 706-712.
7. Lorena SL, Figueiredo MJ, Almeida JR, et al. Autonomic function in patients with functional dyspepsia assessed by 24-hour heart rate

variability. Dig Dis Sci 2002; 47: 27-31.
8. Murray CD, Flynn J, Ratcliffe L, et al. Effects of acute physical and psychological stress and its influence on autonomic outflow to the gut in irritable bowel syndrome. Gastroenterology 2004; 127: 1695-1703.
9. Buysschaert M, Donckier J, Dive A, et al. Gastric acid and pancreatic polypeptide responses to sham feeding are impaired in diabetic subjects with autonomic neuropathy. Diabetes 1985; 34: 1181-1185.
10. Ziegler D, Schadewaldt P, Pour Mirza A, et al. [13C]Octanoic acid breath test for non-invasive assessment of gastric emptying in diabetic patients; validation and relationship to gastric symptoms and cardiovascular autonomic function. Diabetologia 1996; 39: 823-830.
11. Hjelland I, Oveland NP, Leversen K, et al. Insulin-induced hypoglycemia stimulates gastric vagal activity and motor function without increasing cardiac vagal activity. Digestion 2005; 72: 43-48.
12. Konturek SJ, Bielanski W, Solomon TE. Effects of antral mucosectomy, L-346, 718 and atropine on cephalic phase of gastric and pancreatic secretion in dogs. Gastroenterology 1990; 98: 47-55.
13. Liu S, Peng S, Hou X, et al. Transcutaneous electroacupuncture improves dyspeptic symptoms and increases high frequency heart rate variability in patients with functional dyspepsia. Neurogastroenterol Motil 2008; 20: 1204-1211. 75
14. Chen J, Song GQ, Yin J, et al. Electroacupuncture improves impaired gastric motility and slow waves induced by rectal distension in dogs. Am J Physiol Gastrointest Liver Physiol 2008; 295: G614-G620.
15. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Eur Heart J 1996; 17: 354-381.
16. Muth ER, Thayer JF, Stern RM, et al. The effect of autonomic nervous system activity on gastric myoelectrical activity: does the spectral reverse hypothesis hold for the stomach? Biological Psychology 1998; 71: 265-278.
17. Iriki M. Regional differentiation of sympathetic efferents under various natural and experimental conditions. Shinkei Kenkyu No Shinpo 1989; 33: 196-206.
18. Lu CL, Zou X, Orr WC, et al. Postprandial changes of sympathovagal balance measured by heart rate variability. Dig Dis Sci 1999; 44: 857-861.
19. Schwartz TW. Pancreatic polypeptide: A hormone under vagal control. Gastroenterology 1983; 85: 1411-1425.
20. Schwartz TW, Stenquist B, Olbe L, et al. Synchronous oscillations in the basal secretion of pancreatic-polypeptide and gastric acid.
Depression by cholinergic blockade of pancreatic-polypeptide concentrations in plasma. Gastroenterology 1979; 76: 14-19.
21. Levitt NS, Vinik AI, Sive AA, et al. Impaired pancreatic polypeptide response to insulin induced hypoglycemia in diabetic autonomic neuropathy. J Clin Endocrinol Metab 1980; 50: 445-449.
22. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-432.
23. Sobhani I, Bado A, Vissuzaine C, et al. Leptin secretion and leptin receptor in the human stomach. Gut 2000; 47: 178-183.
24. Cinti S, Matteis RD, Pico C, et al. Secretory granules of endocrine and chief cells of human stomach mucosa contain leptin. Int J Obes Relat Metab Disord 2000; 24: 789-793.
25. Sobhani I, Buyse M, Goiot H, et al. Vagal stimulation rapidly increases leptin secretion in human stomach. Gastroenterology 2002; 122: 259-263.
26. Cummings DE, Purnell JQ, Frayo RS, et al. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001; 50: 1714-1719.
27. Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407: 908-913.
28. Murray CD, Martin NM, Patterson M, et al. Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study. Gut 2005; 54: 1693-1698.
29. Paine P, Kishor J, Worthen SF, et al. Exploring relationships for visceral and somatic pain with autonomic control and personality. Pain 2009; 144: 236-244.