Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats

Yuan Yuan Zhou, Natalie J. Wanner, Ying Xiao, Xuan-Zheng Shi, Xing Hong Jiang, Jian Guo Gu, Guang Yin Xu

Research output: Contribution to journalArticle

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Abstract

AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates. METHODS: Six to nine week-old male Sprague Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 °C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (NLX) or NLX methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments. RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 ± 0.2, 1.3 ± 0.2, 1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 ± 0.1, 2.5 ± 0.1, 2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 ± 0.2 vs 0.7 ± 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 ± 0.2 vs 1.5 ± 0.2, P = 0.00 163; AWRs at 60 mmHg: 3.1 ± 0.2 vs 1.9 ± 0.1, P = 0.003; AWRs at 80 mmHg: 3.6 ± 0.1 vs 2.4 ± 0.2, P = 0.0023; electromyographic (EMG) at 20 mmHg: 24 ± 4.7 vs 13.8 ± 3.5; EMG at 40 mmHg: 60.2 ± 6.6 vs 30 ± 4.9, P = 0.00 523; EMG at 60 mmHg: 83 ± 10 vs 39.8 ± 5.9, P = 0.00 029; EMG at 80 mmHg: 94.3 ± 10.8 vs 49.6 ± 5.9, P = 0.00 021]. In addition, EA at the acupuncture point BL-43 with same parameters did not alleviate visceral hypersensitivity in HIS rats. EA in healthy rats also did not have any effect on AWR scores to colorectal distention at distention pressures of 20 and 40 mmHg. The EA-mediated analgesic effect was blocked by pretreatment with NLX in HIS rats [AWR scores pretreated with NLX vs normal saline (NS) were 2.0 vs 0.70 ± 0.20, 2.80 ± 0.12 vs 1.50 ± 0.27, 3 vs 2.00 ± 0.15 and 3.60 ± 0.18 vs 2.60 ± 0.18 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.0087, 0.0104, 0.0117 and 0.0188 for 20, 40, 60 and 80 mmHg, respectively]. Furthermore, EA-mediated analgesic effect was completely reversed by administration of m-NLX, a peripherally restricted opioid antagonist (EMG pretreated with m-NLX vs NS were 30.84 ± 4.39 vs 13.33 ± 3.88, 74.16 ± 9.04 vs 36.28 ± 8.01, 96.45 ± 11.80 vs 50.19 ± 8.28, and 111.59 ± 13.79 vs 56.42 ± 8.43 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.05 026, 0.00 034, 0.00 005, 0.000 007 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg, respectively). CONCLUSION: EA given at classical acupoint ST-36 alleviates stress-induced visceral pain, which is most likely mediated by opioid pathways in the periphery.

Original languageEnglish (US)
Pages (from-to)7201-7211
Number of pages11
JournalWorld Journal of Gastroenterology
Volume18
Issue number48
DOIs
StatePublished - 2012

Fingerprint

Electroacupuncture
Abdominal Reflex
Opioid Analgesics
Hypersensitivity
Naloxone
Acupuncture Points
Pressure
Hindlimb
Analgesics
Visceral Pain
Opioid Peptides
Narcotic Antagonists
Electromyography
Dehydration
Sprague Dawley Rats
Placebos

Keywords

  • Electroacupuncture
  • Irritable bowel syndrome
  • Opioid pathway
  • Stress
  • Visceral pain

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats. / Zhou, Yuan Yuan; Wanner, Natalie J.; Xiao, Ying; Shi, Xuan-Zheng; Jiang, Xing Hong; Gu, Jian Guo; Xu, Guang Yin.

In: World Journal of Gastroenterology, Vol. 18, No. 48, 2012, p. 7201-7211.

Research output: Contribution to journalArticle

Zhou, Yuan Yuan ; Wanner, Natalie J. ; Xiao, Ying ; Shi, Xuan-Zheng ; Jiang, Xing Hong ; Gu, Jian Guo ; Xu, Guang Yin. / Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats. In: World Journal of Gastroenterology. 2012 ; Vol. 18, No. 48. pp. 7201-7211.
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title = "Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats",
abstract = "AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates. METHODS: Six to nine week-old male Sprague Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 °C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (NLX) or NLX methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments. RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 ± 0.2, 1.3 ± 0.2, 1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 ± 0.1, 2.5 ± 0.1, 2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 ± 0.2 vs 0.7 ± 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 ± 0.2 vs 1.5 ± 0.2, P = 0.00 163; AWRs at 60 mmHg: 3.1 ± 0.2 vs 1.9 ± 0.1, P = 0.003; AWRs at 80 mmHg: 3.6 ± 0.1 vs 2.4 ± 0.2, P = 0.0023; electromyographic (EMG) at 20 mmHg: 24 ± 4.7 vs 13.8 ± 3.5; EMG at 40 mmHg: 60.2 ± 6.6 vs 30 ± 4.9, P = 0.00 523; EMG at 60 mmHg: 83 ± 10 vs 39.8 ± 5.9, P = 0.00 029; EMG at 80 mmHg: 94.3 ± 10.8 vs 49.6 ± 5.9, P = 0.00 021]. In addition, EA at the acupuncture point BL-43 with same parameters did not alleviate visceral hypersensitivity in HIS rats. EA in healthy rats also did not have any effect on AWR scores to colorectal distention at distention pressures of 20 and 40 mmHg. The EA-mediated analgesic effect was blocked by pretreatment with NLX in HIS rats [AWR scores pretreated with NLX vs normal saline (NS) were 2.0 vs 0.70 ± 0.20, 2.80 ± 0.12 vs 1.50 ± 0.27, 3 vs 2.00 ± 0.15 and 3.60 ± 0.18 vs 2.60 ± 0.18 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.0087, 0.0104, 0.0117 and 0.0188 for 20, 40, 60 and 80 mmHg, respectively]. Furthermore, EA-mediated analgesic effect was completely reversed by administration of m-NLX, a peripherally restricted opioid antagonist (EMG pretreated with m-NLX vs NS were 30.84 ± 4.39 vs 13.33 ± 3.88, 74.16 ± 9.04 vs 36.28 ± 8.01, 96.45 ± 11.80 vs 50.19 ± 8.28, and 111.59 ± 13.79 vs 56.42 ± 8.43 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.05 026, 0.00 034, 0.00 005, 0.000 007 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg, respectively). CONCLUSION: EA given at classical acupoint ST-36 alleviates stress-induced visceral pain, which is most likely mediated by opioid pathways in the periphery.",
keywords = "Electroacupuncture, Irritable bowel syndrome, Opioid pathway, Stress, Visceral pain",
author = "Zhou, {Yuan Yuan} and Wanner, {Natalie J.} and Ying Xiao and Xuan-Zheng Shi and Jiang, {Xing Hong} and Gu, {Jian Guo} and Xu, {Guang Yin}",
year = "2012",
doi = "10.3748/wjg.v18.i48.7201",
language = "English (US)",
volume = "18",
pages = "7201--7211",
journal = "World Journal of Gastroenterology",
issn = "1007-9327",
publisher = "WJG Press",
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TY - JOUR

T1 - Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats

AU - Zhou, Yuan Yuan

AU - Wanner, Natalie J.

AU - Xiao, Ying

AU - Shi, Xuan-Zheng

AU - Jiang, Xing Hong

AU - Gu, Jian Guo

AU - Xu, Guang Yin

PY - 2012

Y1 - 2012

N2 - AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates. METHODS: Six to nine week-old male Sprague Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 °C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (NLX) or NLX methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments. RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 ± 0.2, 1.3 ± 0.2, 1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 ± 0.1, 2.5 ± 0.1, 2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 ± 0.2 vs 0.7 ± 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 ± 0.2 vs 1.5 ± 0.2, P = 0.00 163; AWRs at 60 mmHg: 3.1 ± 0.2 vs 1.9 ± 0.1, P = 0.003; AWRs at 80 mmHg: 3.6 ± 0.1 vs 2.4 ± 0.2, P = 0.0023; electromyographic (EMG) at 20 mmHg: 24 ± 4.7 vs 13.8 ± 3.5; EMG at 40 mmHg: 60.2 ± 6.6 vs 30 ± 4.9, P = 0.00 523; EMG at 60 mmHg: 83 ± 10 vs 39.8 ± 5.9, P = 0.00 029; EMG at 80 mmHg: 94.3 ± 10.8 vs 49.6 ± 5.9, P = 0.00 021]. In addition, EA at the acupuncture point BL-43 with same parameters did not alleviate visceral hypersensitivity in HIS rats. EA in healthy rats also did not have any effect on AWR scores to colorectal distention at distention pressures of 20 and 40 mmHg. The EA-mediated analgesic effect was blocked by pretreatment with NLX in HIS rats [AWR scores pretreated with NLX vs normal saline (NS) were 2.0 vs 0.70 ± 0.20, 2.80 ± 0.12 vs 1.50 ± 0.27, 3 vs 2.00 ± 0.15 and 3.60 ± 0.18 vs 2.60 ± 0.18 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.0087, 0.0104, 0.0117 and 0.0188 for 20, 40, 60 and 80 mmHg, respectively]. Furthermore, EA-mediated analgesic effect was completely reversed by administration of m-NLX, a peripherally restricted opioid antagonist (EMG pretreated with m-NLX vs NS were 30.84 ± 4.39 vs 13.33 ± 3.88, 74.16 ± 9.04 vs 36.28 ± 8.01, 96.45 ± 11.80 vs 50.19 ± 8.28, and 111.59 ± 13.79 vs 56.42 ± 8.43 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.05 026, 0.00 034, 0.00 005, 0.000 007 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg, respectively). CONCLUSION: EA given at classical acupoint ST-36 alleviates stress-induced visceral pain, which is most likely mediated by opioid pathways in the periphery.

AB - AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates. METHODS: Six to nine week-old male Sprague Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 °C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (NLX) or NLX methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments. RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 ± 0.2, 1.3 ± 0.2, 1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 ± 0.1, 2.5 ± 0.1, 2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 ± 0.2 vs 0.7 ± 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 ± 0.2 vs 1.5 ± 0.2, P = 0.00 163; AWRs at 60 mmHg: 3.1 ± 0.2 vs 1.9 ± 0.1, P = 0.003; AWRs at 80 mmHg: 3.6 ± 0.1 vs 2.4 ± 0.2, P = 0.0023; electromyographic (EMG) at 20 mmHg: 24 ± 4.7 vs 13.8 ± 3.5; EMG at 40 mmHg: 60.2 ± 6.6 vs 30 ± 4.9, P = 0.00 523; EMG at 60 mmHg: 83 ± 10 vs 39.8 ± 5.9, P = 0.00 029; EMG at 80 mmHg: 94.3 ± 10.8 vs 49.6 ± 5.9, P = 0.00 021]. In addition, EA at the acupuncture point BL-43 with same parameters did not alleviate visceral hypersensitivity in HIS rats. EA in healthy rats also did not have any effect on AWR scores to colorectal distention at distention pressures of 20 and 40 mmHg. The EA-mediated analgesic effect was blocked by pretreatment with NLX in HIS rats [AWR scores pretreated with NLX vs normal saline (NS) were 2.0 vs 0.70 ± 0.20, 2.80 ± 0.12 vs 1.50 ± 0.27, 3 vs 2.00 ± 0.15 and 3.60 ± 0.18 vs 2.60 ± 0.18 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.0087, 0.0104, 0.0117 and 0.0188 for 20, 40, 60 and 80 mmHg, respectively]. Furthermore, EA-mediated analgesic effect was completely reversed by administration of m-NLX, a peripherally restricted opioid antagonist (EMG pretreated with m-NLX vs NS were 30.84 ± 4.39 vs 13.33 ± 3.88, 74.16 ± 9.04 vs 36.28 ± 8.01, 96.45 ± 11.80 vs 50.19 ± 8.28, and 111.59 ± 13.79 vs 56.42 ± 8.43 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.05 026, 0.00 034, 0.00 005, 0.000 007 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg, respectively). CONCLUSION: EA given at classical acupoint ST-36 alleviates stress-induced visceral pain, which is most likely mediated by opioid pathways in the periphery.

KW - Electroacupuncture

KW - Irritable bowel syndrome

KW - Opioid pathway

KW - Stress

KW - Visceral pain

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