Evidence Details for Map2k1
PMID Title Journal Year Abstract
27978835 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. doi: 10.1186/s12906-016-1508-z. 2016 Dec 15 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."

Evidence Sentence: Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats
Evidence Sentence: 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.
Evidence Sentence: 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.
Evidence Sentence: To examine whether MEK1 is activated in the hippocampus and hypothalamus after CCI and EA, we performed a western blot analysis with antibodies targeting the total MEK1 expression and the dually phosphorylated MEK1 (pMEK1, Ser217/221) because phosphorylation at Ser-217 and Ser-221 positively regulates MEK1 activity.
Evidence Sentence: This reduction was significantly reversed from day 2 to 4 of EA treatment, and MEK1 activation in rats with EA was higher than that in the CON group animals (P < 0.01).
Evidence Sentence: After normalizing pMEK1 levels to total MEK1 levels (pMEK1 versus MEK1), the same results were obtained as above (Fig.
Evidence Sentence: 3a) and no significant changes were found in total MEK1 expression levels (Fig.
Evidence Sentence: To detect the different role of MEK1 at different stages of EA intervention, the selective MEK1 inhibitor PD98059 was injected into the contralateral hippocampus on the first 3 days or on day 8, 9, and 10 of EA treatment separately.
Evidence Sentence: After hippocampal microinjection of MEK1 antagonist PD98059, there were no apparent differences in the levels of hypothalamic pMEK1 protein between the PD98059 groups and their corresponding DMSO control groups on days 3, 10, and 12 (P > 0.05,).