[an error occurred while processing this directive]

Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (4): 416-423.doi: 10.3736/jcim20120410

Previous Articles     Next Articles

Effects of electroacupuncture on expression of c-fos protein and N-methyl-D-aspartate receptor 1 in the rostral ventromedia medulla of rats with chronic visceral hyperalgesia

De-bo Qi, Wei-min Li()   

  1. Laboratory of Neural Network and Systems Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Received:2011-12-05 Accepted:2011-12-27 Online:2012-04-20 Published:2018-04-15

RichHTML

1

PDF (PC)

98

Like

Objective: Acupuncture has been clinically proved to be effective in treating abdominal pain in patients with irritable bowel syndrome (IBS). However, its neurobiological mechanism remains largely unexplored. The aim of this study was to investigate the effect of electroacupuncture (EA) in relieving chronic visceral hyperalgesia and the possible involvement of N-methyl-D-aspartate receptor 1 (NR1) in rostral ventromedia medulla (RVM) of the brain in an IBS rat model.
Methods: To establish the IBS rat model, male Sprague-Dawley neonatal rats received colon mechanical irritation on a daily basis from the 9th to the 22nd day after their birth. After a resting period of another two to four weeks, behavioral tests of pain threshold pressure (PTP) and abdominal withdrawal reflex (AWR) responding to colorectal distention (CRD) stimuli were conducted to judge the colorectal sensitive situation. Then administration of EA at acupoints of Zusanli (ST36) and Shangjuxu (ST37) bilaterally in the hind limbs was repeated four times every other day, while sham-EA was done by inserting needles at similar acupoints without electrical stimulation. Immunohistochemical method was used to display the expression of proto-oncogene protein c-fos and NR1 in RVM of rats.
Results: The results demonstrated that the PTP values and AWR scores, in response to the CRD stimuli, significantly decreased and increased, respectively (P<0.01, P<0.01), while the number of immunoreactive neurons of c-fos protein and NR1 significantly increased in nucleus reticularis gigantocellularis (Gi), nucleus lateralis paragigantocellulari (LPGi), nucleus reticularis gigantocellularis pars alpha (GiA) and nucleus raphe magnus (NRM) of RVM in IBS model rats compared with the normal rats (P<0.05). After EA treatment, PTP values and AWR scores significantly increased and decreased, respectively (P<0.01, P<0.05); the number of immunoreactive neurons of c-fos and NR1 significantly decreased respectively in Gi, LPGi and GiA and in Gi, LPGi, GiA and NRM (P<0.05). No such effects on PTP values, AWR scores and the number of immunoreactive neurons of c-fos and NR1 were observed after sham-EA treatment.
Conclusion: These data provide the evidence that EA can relieve chronic visceral hyperalgesia in rats with IBS, and such an effect may be correlated with inhibitory modulation of hyperactivity of neurons by means of down-regulating the high expression of NR1 in RVM of IBS model rats.

Key words: receptors, N-methyl-D-aspartate, hyperalgesia, acupuncture therapy, proto-oncogene protein c-fos, irritable bowel syndrome, rats

Figure 1

RVM in the brainstem sliced at the rostral end of the Ⅳ ventricle RVM: rostral ventromedia medulla; Gi: nucleus reticularis gigantocellularis; NRM: nucleus raphe magnus; GiA: nucleus reticularis gigantocellularis pars alpha; LPGi: nucleus lateralis paragigantocellulari; 4V: the Ⅳ ventricle; Sol: solitary tract; Sp5: spinal trigeminal tract; Py: pyramidal tract; RPa: raphe pallidus nucleus; ml: medial lemniscus; 7n: facial nucleus."

Figure 2

PTP values measured in response to continuous colorectal distention Data are represented as mean±standard error of mean, n=8; **P<0.01, vs normal control group; △△P<0.01, vs IBS model control group. PTP: pain threshold pressure; IBS: irritable bowel syndrome; EA: electroacupuncture."

"

Group n AWR score
20 mmHg 40 mmHg 60 mmHg 80 mmHg
Normal control 8 0.30±0.09 1.39±0.12 2.26±0.14 3.02±0.22
IBS model control 8 1.24±0.18** 2.17±0.17** 3.04±0.11** 3.78±0.08**

"

Group n AWR score
20 mmHg 40 mmHg 60 mmHg 80 mmHg
EA treatment
Before 8 1.27±0.21 2.21±0.19 2.98±0.11 3.77±0.10
After 8 0.33±0.09▲□ 1.36±0.10▲□ 2.25±0.11▲□ 2.88±0.10▲□
Sham-EA treatment
Before 8 1.29±0.08 2.27±0.15 2.81±0.09 3.75±0.09
After 8 0.69±0.10 1.87±0.11 2.48±0.13 3.15±0.21

Figure 3

Samples of microphotographs with the c-fos- (A-D) and NR1- (E-H) immunoreactive neurons of the RVM in different groups (Light microscopy, ×25) The images of immunohistochemical results were taken under the light microscopy. The arrows show c-fos- or NR1-immunoreactive neurons. N: Normal control group; M: IBS model control group; EA: IBS model rats after EA treament; SEA: IBS model rats after sham-EA treatment; RVM: rostral ventromedia medulla; NR1: N-methyl-D-aspartate receptor 1; IBS: irritable bowel syndrome; EA: electroacupuncture."

"

Group n c-fos
Gi LPGi GiA NRM
Normal control 8 34.62±2.02 29.13±1.25 9.52±0.80 3.23±0.45
IBS model control 8 59.66±3.00* 37.34±1.95* 13.50±1.53* 4.84±0.76*
EA treatment 8 40.84±2.28△ 30.18±1.51△ 9.12±1.20△ 2.68±0.56
Sham-EA treatment 8 50.70±2.52 35.76±1.98 13.86±1.33 2.46±0.34

"

Group n NR1
Gi LPGi GiA NRM
Normal control 8 23.05±1.75 14.28±1.28 4.85±0.75 1.73±0.31
IBS model control 8 36.44±1.99* 21.15±1.45* 8.88±0.98* 3.00±0.50*
EA treatment 8 24.03±1.38△ 13.93±1.20△ 3.23±0.61△ 1.08±0.28△
Sham-EA treatment 8 36.45±1.40 24.20±1.50 8.10±0.83 3.08±0.48
[1] Verne GN, Robinson ME, Price DD . Hypersensitivity to visceral and cutaneous pain in the irritable bowel syndrome. Pain. 2001; 93(1):7-14.
doi: 10.1016/S0304-3959(01)00285-8
[2] Sengupta JN . Visceral pain: the neurophysiological mechanism. Handb Exp Pharmacol. 2009; ( 194) : 31-74.
[3] Hungin AP, Whorwell PJ, Tack J, Mearin F . The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther. 2003 ; 17(5) : 643-650.
doi: 10.1046/j.1365-2036.2003.01456.x
[4] Gwee KA, Lu CL, Ghoshal UC . Epidemiology of irritable bowel syndrome in Asia: something old, something new, something borrowed.J Gastroenterol Hepatol. 2009; 24(10) : 1601-1607.
doi: 10.1111/jgh.2009.24.issue-10
[5] Cash B, Sullivan S, Barghout V . Total costs of IBS: employer and managed care perspective. Am J Manag Care. 2005; 11(1 Suppl) : S7-S16.
[6] Talley NJ, Gabriel SE, Harmsen WS, Zinsmeister AR, Evans RW . Medical costs in community subjects with irritable bowel syndrome. Gastroenterology. 1995; 109(6):1736-1741.
doi: 10.1016/0016-5085(95)90738-6
[7] Schneider A, Weiland C, Enck P, Joos S, Streitberger K, Maser-Gluth C, Zipfel S, Bagheri S, Herzog W, Friederich HC . Neuroendocrinological effects of acupuncture treatment in patients with irritable bowel syndrome. Complement Ther Med. 2007; 15(4):255-263.
doi: 10.1016/j.ctim.2006.12.002
[8] Xiao WB, Liu YL . Rectal hypersensitivity reduced by acupoint TENS in patients with diarrhea-predominant irritable bowel syndrome: a pilot study. Dig Dis Sci. 2004; 49(2) : 312-319.
doi: 10.1023/B:DDAS.0000017458.55517.33
[9] Musial F, Tao I, Dobos G . Is the analgesic effect of acupuncture a placebo effect? Schmerz. 2009 ; 23(4):341-346.
doi: 10.1007/s00482-009-0810-9
[10] Rohrbock RB, Hammer J, Vogelsang H, Talley NJ, Hammer HF . Acupuncture has a placebo effect on rectal perception but not on distensibility and spatial summation: a study in health and IBS. Am J Gastroenterol. 2004; 99(10):1990-1997.
doi: 10.1111/ajg.2004.99.issue-10
[11] Zhuo M, Gebhart GF . Facilitation and attenuation of a visceral nociceptive reflex from the rostroventral medulla in the rat. Gastroenterology. 2002 ; 122(4):1007-1019.
doi: 10.1053/gast.2002.32389
[12] Zhuo M, Sengupta JN, Gebhart GF . Biphasic modulation of spinal visceral nociceptive transmission from the rostroventral medial medulla in the rat.J Neurophysiol. 2002; 87(5) : 2225-2236.
doi: 10.1152/jn.2002.87.5.2225
[13] Urban MO, Coutinho SV, Gebhart GF . Biphasic modulation of visceral nociception by neurotensin in rat rostral ventromedial medulla.J Pharmacol Exp Ther. 1999 ; 290(1):207-213.
[14] Coutinho SV, Urban MO, Gebhart GF . Role of glutamate receptors and nitric oxide in the rostral ventromedial medulla in visceral hyperalgesia. Pain. 1998; 78(1):59-69.
doi: 10.1016/S0304-3959(98)00137-7
[15] Coutinho SV, Urban MO, Gebhart GF . The role of CNS NMDA receptors and nitric oxide in visceral hyperalgesia. Eur J Pharmacol. 2001 ; 429(1-3) : 319-325.
doi: 10.1016/S0014-2999(01)01331-0
[16] Porreca F, Ossipov MH, Gebhart GF . Chronic pain and medullary descending facilitation. Trends Neurosci. 2002; 25(6) : 319-325.
doi: 10.1016/S0166-2236(02)02157-4
[17] Al-Chaer ED, Kawasaki M, Pasricha PJ . A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology. 2000; 119(5):1276-1285.
doi: 10.1053/gast.2000.19576
[18] Cui KM, Li WM, Gao X, Chung K, Chung JM, Wu GC . Electro-acupuncture relieves chronic visceral hyperalgesia in rats. Neurosci Lett. 2005; 376(1):20-23.
doi: 10.1016/j.neulet.2004.11.018
[19] Zhou J Li WM. Influence of electroacupuncture on expression of N-methyl-D-aspartatic receptors in the spinal cord of irritable bowel syndrome rat. Shanghai Zhen Jiu Za Zhi. 2008; 27(6): 38-40. Chinese with abstract in English.
周娟, 李为民 . 电针对肠易激综合征大鼠脊髓NMDA 受体表达的影响.上海针灸杂志. 2008; 27(6):38-40.
[20] Sagar SM, Sharp FR, Curran T . Expression of c-fos protein in brain: metabolic mapping at the cellular level. Science. 1988; 240(4857):1328-1331.
doi: 10.1126/science.3131879
[21] Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed. Waltham: Academic Press. 2007 : 270-298.
[22] Drossman DA . Chronic functional abdominal pain. Am J Gastroenterol. 1996; 91(11):2270-2281.
[23] Winston J, Shenoy M, Medley D, Naniwadekar A, Pasricha PJ . The vanilloid receptor initiates and maintains colonic hypersensitivity induced by neonatal colon irritation in rats. Gastroenterology. 2007; 132(2):615-627.
doi: 10.1053/j.gastro.2006.11.014
[24] Chung EK, Bian ZX, Xu HX, Sung JJ . Neonatal maternal separation increases brain-derived neurotrophic factor and tyrosine kinase receptor B expression in the descending pain modulatory system. Neurosignals. 2009; 17(3) : 213-221.
doi: 10.1159/000224631
[1] Na Wu , Lu Song , Xin-xin Yang, Jiang-lei Wei , Zhen-guo Liu. Effects of Chinese herbal medicine Tianqi Pingchan Granule on G protein-coupled receptor kinase 6 involved in the prevention of levodopa-induced dyskinesia in rats with Parkinson disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1018-1024.
[2] Lawrence A. Olatunji, Taofeek O. Usman, Joseph O. Adebayo, Victoria A. Olatunji . Effects of aqueous extract of Hibiscus sabdariffa on renal Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in Wistar rats. Journal of Chinese Integrative Medicine, 2012, 10(9): 1049-1055.
[3] Dhirender Kaushik, Ajay Kumar, Pawan Kaushik, Avatar C. Rana. Anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg. Journal of Chinese Integrative Medicine, 2012, 10(9): 1056-1060.
[4] Chan Chen, Chang-xun Chen, Xi-min Wu, Rui Wang, Yi-ming Li. Effects of extracts of Radix Scrophulariae on blood pressure in spontaneously hypertensive rats and the underlying mechanisms. Journal of Chinese Integrative Medicine, 2012, 10(9): 1009-1017.
[5] Jian-sheng Li, Ya Li, Su-yun Li, Yuan-yuan Wang, Li Deng, Yan-ge Tian, Su-li Jiang , Ying Wang. Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1039-1048.
[6] Zhang-ling Zhou, Cheng-xin Li, Yue-bo Jiang, Cong Zuo, Yun Cai, Rui Wang. Correlation between facial nerve functional evaluation and efficacy evaluation of acupuncture treatment for Bell’s palsy. Journal of Chinese Integrative Medicine, 2012, 10(9): 997-1002.
[7] Karuna A. Talpate, Uma A. Bhosale, Mandar R. Zambare. Clitorea ternatea, a herb from Indian folklore, improves streptozotocin-induced diabetes and diabetes-induced cognitive decline in rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 939-947.
[8] Ming T. Tan , Jian-ping Liu , Lixing Lao. Adequate application of quantitative and qualitative statistic analytic methods in acupuncture clinical trials. Journal of Chinese Integrative Medicine, 2012, 10(8): 847-852.
[9] Samuel Joshua Pragasam, Vachana Murunikara, Evan Prince Sabina, Mahaboobkhan Rasool. Antiperoxidative potential of p-coumaric acid, a common dietary phenol, in adjuvant-induced arthritis in rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 932-938.
[10] Zi-hui Li, Jian Wang, Rong-lin Cai, You-wen Wang, Jian-peng Hu. Establishment and evaluation of a rat model of ulcerative colitis with syndrome of dampness stagnancy due to spleen deficiency. Journal of Chinese Integrative Medicine, 2012, 10(8): 918-924.
[11] Meng Li, Ling Hu, Rong-lin Cai, Zi-jian Wu, Ke-ming Wang. Effects of electro-acupuncture at PC6 and BL15 on nerve electrical activity in spinal dorsal root and norepinephrine and dopamine contents in paraventricular nucleus of hypothalamus in rats with acute myocardial ischemia. Journal of Chinese Integrative Medicine, 2012, 10(8): 874-879.
[12] Xin-min Li, Hui Chen, Yan-yan Ren, Yan-li Lu. Effects of Chinese herbal medicine Xifeng Capsule on multidrug resistance-associated protein 1 expression in hippocampus and cortex of rats with lithium-pilocarpine-induced epilepsy. Journal of Chinese Integrative Medicine, 2012, 10(8): 911-917.
[13] Hong Wang , Jing-tian Ou , Xin Zhao , Ying Guoz , Hao-ping Mao. Vasodilator effect of oroxylin A on thoracic aorta isolated from rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 880-885.
[14] C. Mouli Kalla, Vijaya Tartte, Dattatreya Rao Sirpurkar. Effectiveness of flavonoid-rich leaf extract of Acalypha indica in reversing experimental myocardial ischemia: biochemical and histopathological evidence. Journal of Chinese Integrative Medicine, 2012, 10(7): 784-792.
[15] Mei-jiao Mao, Jun-ping Hu, Cong Wang, Yi-yi Zhang, Ping Liu. Effects of Chinese herbal medicine Guanxinkang on expression of PPARγ-LXRα-ABCA1 pathway in ApoE-knockout mice with atherosclerosis. Journal of Chinese Integrative Medicine, 2012, 10(7): 814-820.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[4] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5] . Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[6] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[7] Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[8] Zhao-guo Li . A discussion of English translation of 1995 and 1997 Chinese National Standards of Traditional Chinese Medical Terminologies for Clinical Diagnosis and Treatment. Journal of Chinese Integrative Medicine, 2010, 8(11): 1090-1096
[9] Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205
[10] Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228
[an error occurred while processing this directive]