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Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats.
BMC Complement Altern Med. 2016 Dec 15; 16(1):517.BC

Abstract

BACKGROUND

Electroacupuncture (EA) intervention can relieve a variety of pain; however, optimal EA protocols have not been clearly determined. In addition, although central mitogen-activated protein kinase kinase (MEK) signaling has been shown to be involved in the antinociceptive effect of acupuncture stimulation, its characteristics at different time-points of EA intervention have not been fully elucidated. Therefore, the present study investigated the relationship between the effects of different numbers of EA intervention sessions and the activation of MEK1 in the hippocampus and hypothalamus in a rat model of neuropathic pain.

METHODS

After ligation of the left sciatic nerve, which induces chronic constriction injury (CCI), the acupoints Zusanli (ST36) and Yanglingquan (GB34) were applied. The thermal withdrawal latency of the hind paw was used to evaluate the effect of EA on pain thresholds. Intra-hippocampus microinjection of PD98059, a MEK inhibitor, was performed to validate the involvement of MEK in EA analgesia. The hippocampus and hypothalamus were harvested to examine the phosphorylation levels of MEK (pMEK) by western blotting.

RESULTS

In CCI rats, the thermal pain threshold of the affected hind paw decreased significantly relative to the control. Following subsequent daily EA interventions, CCI-induced ipsilateral hyperalgesia was markedly improved from day 4 and the analgesic effect of EA lasted 3 days after cessation of EA. Four sessions of EA markedly suppressed CCI-induced decrease of hippocampal pMEK1 (normalized to the total MEK level). In contrast, successive sessions of EA intervention gradually down-regulated the CCI-induced up-regulation of hypothalamic pMEK1 along with the increase numbers of EA intervention. However, EA did not exert the same analgesic effect after microinjection of PD98059 into the contralateral hippocampus during the first 3 days of EA intervention.

CONCLUSIONS

EA intervention can induce time-dependent cumulative analgesia in neuropathic pain rats after 4 successive sessions of daily EA intervention, which is at least in part related to the activation of hippocampal MEK1.

Authors+Show Affiliations

Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.College of Acupuncture & Moxibustion and Tui-na, Hunan University of Chinese Medicine, Changsha, 410208, Hunan Province, China. The First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou, 412012, Hunan Province, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China.Meridian Research Center, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China. 13521898023@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27978835

Citation

Gao, Yong-Hui, et al. "Activation of Hippocampal MEK1 Contributes to the Cumulative Antinociceptive Effect of Electroacupuncture in Neuropathic Pain Rats." BMC Complementary and Alternative Medicine, vol. 16, no. 1, 2016, p. 517.
Gao YH, Li CW, Wang JY, et al. Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats. BMC Complement Altern Med. 2016;16(1):517.
Gao, Y. H., Li, C. W., Wang, J. Y., Kan, Y., Tan, L. H., Jing, X. H., & Liu, J. L. (2016). Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats. BMC Complementary and Alternative Medicine, 16(1), 517.
Gao YH, et al. Activation of Hippocampal MEK1 Contributes to the Cumulative Antinociceptive Effect of Electroacupuncture in Neuropathic Pain Rats. BMC Complement Altern Med. 2016 Dec 15;16(1):517. PubMed PMID: 27978835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats. AU - Gao,Yong-Hui, AU - Li,Cheng-Wen, AU - Wang,Jun-Ying, AU - Kan,Yu, AU - Tan,Lian-Hong, AU - Jing,Xiang-Hong, AU - Liu,Jun-Ling, Y1 - 2016/12/15/ PY - 2016/06/30/received PY - 2016/12/02/accepted PY - 2016/12/17/entrez PY - 2016/12/17/pubmed PY - 2017/1/20/medline KW - Acupuncture analgesia KW - Cumulative effect KW - Hippocampus KW - Mitogen-activated protein kinase kinase 1 KW - Neuropathic pain SP - 517 EP - 517 JF - BMC complementary and alternative medicine JO - BMC Complement Altern Med VL - 16 IS - 1 N2 - BACKGROUND: Electroacupuncture (EA) intervention can relieve a variety of pain; however, optimal EA protocols have not been clearly determined. In addition, although central mitogen-activated protein kinase kinase (MEK) signaling has been shown to be involved in the antinociceptive effect of acupuncture stimulation, its characteristics at different time-points of EA intervention have not been fully elucidated. Therefore, the present study investigated the relationship between the effects of different numbers of EA intervention sessions and the activation of MEK1 in the hippocampus and hypothalamus in a rat model of neuropathic pain. METHODS: After ligation of the left sciatic nerve, which induces chronic constriction injury (CCI), the acupoints Zusanli (ST36) and Yanglingquan (GB34) were applied. The thermal withdrawal latency of the hind paw was used to evaluate the effect of EA on pain thresholds. Intra-hippocampus microinjection of PD98059, a MEK inhibitor, was performed to validate the involvement of MEK in EA analgesia. The hippocampus and hypothalamus were harvested to examine the phosphorylation levels of MEK (pMEK) by western blotting. RESULTS: In CCI rats, the thermal pain threshold of the affected hind paw decreased significantly relative to the control. Following subsequent daily EA interventions, CCI-induced ipsilateral hyperalgesia was markedly improved from day 4 and the analgesic effect of EA lasted 3 days after cessation of EA. Four sessions of EA markedly suppressed CCI-induced decrease of hippocampal pMEK1 (normalized to the total MEK level). In contrast, successive sessions of EA intervention gradually down-regulated the CCI-induced up-regulation of hypothalamic pMEK1 along with the increase numbers of EA intervention. However, EA did not exert the same analgesic effect after microinjection of PD98059 into the contralateral hippocampus during the first 3 days of EA intervention. CONCLUSIONS: EA intervention can induce time-dependent cumulative analgesia in neuropathic pain rats after 4 successive sessions of daily EA intervention, which is at least in part related to the activation of hippocampal MEK1. SN - 1472-6882 UR - https://www.unboundmedicine.com/medline/citation/27978835/Activation_of_hippocampal_MEK1_contributes_to_the_cumulative_antinociceptive_effect_of_electroacupuncture_in_neuropathic_pain_rats_ L2 - https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-016-1508-z DB - PRIME DP - Unbound Medicine ER -