Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats

Abstract

BackgroundElectroacupuncture (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.MethodsAfter 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.ResultsIn 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.ConclusionsEA 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.

The role of miR-190a-5p contributes to diabetic neuropathic pain via targeting SLC17A6

“…The up-down method was used to assess the mechanical sensitivity, which was described previously. 17 , 19 , 20 Briefly, the von Frey filament with logarithmically incremental stiffness was used to measure the paw withdrawal thresholds, 0.04–2.04 g (0.04, 0.07, 0.16, 0.4, 0.60, 1.0, 1.4, 2.04 g); the mid-value of the series was 0.4 g, which was applied first. The animals were firstly adapted for 1 week in the test room, then, the corresponding stimulation method was evaluated in advance for 30 minutes before the formal testing.…”

<p>Brain Metabolism in Rats with Neuropathic Pain Induced by Brachial Plexus Avulsion Injury and Treated via Electroacupuncture</p>

“…Chronic pain is a multidimensional experience that continually affects the sensory, motor, emotional, cognitive, and other functions. [25][26][27] Neuropathic pain following BPAI is one of the most intractable types of chronic pain. [28][29][30][31] Studies have demonstrated that abnormal brain activity is an important aspect of its occurrence/persistence and might be associated with its severity.…”

“…38 The expression of pMEK1 in the hypothalamus was gradually down-regulated following continuous intervention of 2/15Hz EA and the effect was time dependent and cumulative. 42 In the behavioural assessment, MWT was used to detect mechanical allodynia, which has been frequently used in the sensation tests following brachial plexus nerve, median, and ulnar nerves, and sciatic nerve injuries in previous studies. [43][44][45][46] BPAI-induced pain in the injured forelimb subsequently caused central sensitisation and facilitation of pain sensation.…”

A rat model for studying electroacupuncture analgesia on acute visceral hyperalgesia

“…Over the past decades, many studies focused on effects and underlying mechanisms of acupuncture through animal experiments, offering scientific evidences and theoretical support to using acupuncture treatment clinically [ 7 , 14 , 40 ]. Most of them were undergone in the field of somatic pain because of the existence of mature animal models [ 12 , 16 , 20 , 21 , 23 , 33 , 34 ]. For examples, reports showed that acupuncture can alleviate inflammatory pain under the skin and its surrounding tissues [ 20 , 21 , 23 ], joint pain [ 33 , 34 ] and some neuropathic pain in the animal’s limbs [ 12 , 16 ].…”