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Involvement of hippocampal acetylcholinergic receptors in electroacupuncture analgesia in neuropathic pain rats.
Behav Brain Funct. 2016 Apr 12; 12(1):13.BB

Abstract

BACKGROUND

Cumulating evidence has shown a close correlation between electroacupuncture stimulation (EAS) frequency-specific analgesic effect and central opioid peptides. However, the actions of hippocampal acetylcholinergic receptors have not been determined. This study aims to observe the effect of different frequencies of EAS on the expression of hippocampal muscarinic and nicotinic acetylcholinergic receptors (mAChRs, nAChRs) in neuropathic pain rats for revealing their relationship.

METHODS

Forty male Wistar rats were randomly and equally divided into sham, CCI model, 2, 2/15 and 100 HzEA groups. The neuropathic pain model was established by ligature of the left sciatic nerve to induce chronic constriction injury (CCI). EAS was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) for 30 min, once daily for 14 days except weekends. The mechanical pain thresholds (withdrawal latencies, PWLs) of bilateral hindpaws were measured. The expression levels of hippocampal M1 and M2 mAChR, and α4 and β2 nAChR genes and proteins were detected by quantitative RT-PCR and Western blot, separately. The involvement of mAChR and nAChR in the analgesic effect of EAS was confirmed by intra-hippocampal microinjection of M1mAChR antagonist (Pirenzepine) and α4β2 nAChR antagonist (dihydro-beta-erythroidine) respectively.

RESULTS

Following EAS, the CCI-induced increase of difference values of bilateral PWLs on day 6 and 14 was significantly reduced (P < 0.05), with 2/15 Hz being greater than 100 Hz EAS on day 14 (P < 0.05). After 2 weeks' EAS, the decreased expression levels of M1 mAChR mRNA of both 2 and 2/15 Hz groups and M1 mAChR protein of the three EAS groups, α4 AChR mRNA of the 2/15 Hz group and β2 nAChR protein of the three EAS groups were considerably increased (P < 0.05), suggesting an involvement of M1 mAChR and β2 nAChR proteins in EAS-induced pain relief. No significant changes were found in the expression of M2 mAChR mRNA and protein, α4 nAChR protein and β2 nAChR mRNA after CCI and EAS (P > 0.05). The analgesic effect of EAS was abolished by intra-hippocampal microinjection of M1mAChR and α4β2 nAChR antagonists respectively.

CONCLUSIONS

EAS of ST36-GB34 produces a cumulative analgesic effect in neuropathic pain rats, which is frequency-dependent and probably mediated by hippocampal M1 mAChR and β2 nAChR proteins.

Authors+Show Affiliations

Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 16 Nanxiaojie Street, Dongzhimennei, Beijing, 100700, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 16 Nanxiaojie Street, Dongzhimennei, Beijing, 100700, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 16 Nanxiaojie Street, Dongzhimennei, Beijing, 100700, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 16 Nanxiaojie Street, Dongzhimennei, Beijing, 100700, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 16 Nanxiaojie Street, Dongzhimennei, Beijing, 100700, China.Department of Biochemistry and Molecular Biology, Institute of Acu-Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 16 Nanxiaojie Street, Dongzhimennei, Beijing, 100700, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 16 Nanxiaojie Street, Dongzhimennei, Beijing, 100700, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 16 Nanxiaojie Street, Dongzhimennei, Beijing, 100700, China. 13521898023@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27068709

Citation

Chen, Shu Ping, et al. "Involvement of Hippocampal Acetylcholinergic Receptors in Electroacupuncture Analgesia in Neuropathic Pain Rats." Behavioral and Brain Functions : BBF, vol. 12, no. 1, 2016, p. 13.
Chen SP, Kan Y, Zhang JL, et al. Involvement of hippocampal acetylcholinergic receptors in electroacupuncture analgesia in neuropathic pain rats. Behav Brain Funct. 2016;12(1):13.
Chen, S. P., Kan, Y., Zhang, J. L., Wang, J. Y., Gao, Y. H., Qiao, L. N., Feng, X. M., Yan, Y. X., & Liu, J. L. (2016). Involvement of hippocampal acetylcholinergic receptors in electroacupuncture analgesia in neuropathic pain rats. Behavioral and Brain Functions : BBF, 12(1), 13. https://doi.org/10.1186/s12993-016-0096-x
Chen SP, et al. Involvement of Hippocampal Acetylcholinergic Receptors in Electroacupuncture Analgesia in Neuropathic Pain Rats. Behav Brain Funct. 2016 Apr 12;12(1):13. PubMed PMID: 27068709.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of hippocampal acetylcholinergic receptors in electroacupuncture analgesia in neuropathic pain rats. AU - Chen,Shu Ping, AU - Kan,Yu, AU - Zhang,Jian Liang, AU - Wang,Jun Ying, AU - Gao,Yong Hui, AU - Qiao,Li Na, AU - Feng,Xiu Mei, AU - Yan,Ya Xia, AU - Liu,Jun Ling, Y1 - 2016/04/12/ PY - 2015/11/06/received PY - 2016/03/19/accepted PY - 2016/4/13/entrez PY - 2016/4/14/pubmed PY - 2016/10/16/medline KW - Alpha-4 nicotinic AChR (nAChR) KW - Beta-2 nAChR KW - Electroacupuncture analgesia KW - Hippocampus KW - M1 muscarinic acetylcholinergic receptor (M1 mAChR) KW - M2 mAChR KW - Neuropathic pain KW - Stimulating frequencies SP - 13 EP - 13 JF - Behavioral and brain functions : BBF JO - Behav Brain Funct VL - 12 IS - 1 N2 - BACKGROUND: Cumulating evidence has shown a close correlation between electroacupuncture stimulation (EAS) frequency-specific analgesic effect and central opioid peptides. However, the actions of hippocampal acetylcholinergic receptors have not been determined. This study aims to observe the effect of different frequencies of EAS on the expression of hippocampal muscarinic and nicotinic acetylcholinergic receptors (mAChRs, nAChRs) in neuropathic pain rats for revealing their relationship. METHODS: Forty male Wistar rats were randomly and equally divided into sham, CCI model, 2, 2/15 and 100 HzEA groups. The neuropathic pain model was established by ligature of the left sciatic nerve to induce chronic constriction injury (CCI). EAS was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) for 30 min, once daily for 14 days except weekends. The mechanical pain thresholds (withdrawal latencies, PWLs) of bilateral hindpaws were measured. The expression levels of hippocampal M1 and M2 mAChR, and α4 and β2 nAChR genes and proteins were detected by quantitative RT-PCR and Western blot, separately. The involvement of mAChR and nAChR in the analgesic effect of EAS was confirmed by intra-hippocampal microinjection of M1mAChR antagonist (Pirenzepine) and α4β2 nAChR antagonist (dihydro-beta-erythroidine) respectively. RESULTS: Following EAS, the CCI-induced increase of difference values of bilateral PWLs on day 6 and 14 was significantly reduced (P < 0.05), with 2/15 Hz being greater than 100 Hz EAS on day 14 (P < 0.05). After 2 weeks' EAS, the decreased expression levels of M1 mAChR mRNA of both 2 and 2/15 Hz groups and M1 mAChR protein of the three EAS groups, α4 AChR mRNA of the 2/15 Hz group and β2 nAChR protein of the three EAS groups were considerably increased (P < 0.05), suggesting an involvement of M1 mAChR and β2 nAChR proteins in EAS-induced pain relief. No significant changes were found in the expression of M2 mAChR mRNA and protein, α4 nAChR protein and β2 nAChR mRNA after CCI and EAS (P > 0.05). The analgesic effect of EAS was abolished by intra-hippocampal microinjection of M1mAChR and α4β2 nAChR antagonists respectively. CONCLUSIONS: EAS of ST36-GB34 produces a cumulative analgesic effect in neuropathic pain rats, which is frequency-dependent and probably mediated by hippocampal M1 mAChR and β2 nAChR proteins. SN - 1744-9081 UR - https://www.unboundmedicine.com/medline/citation/27068709/Involvement_of_hippocampal_acetylcholinergic_receptors_in_electroacupuncture_analgesia_in_neuropathic_pain_rats_ L2 - https://behavioralandbrainfunctions.biomedcentral.com/articles/10.1186/s12993-016-0096-x DB - PRIME DP - Unbound Medicine ER -