Abstract

Migraine onset is associated with the abnormal release of vasoactive neurotransmitters from perivascular nerves, and these neurotransmitters are involved in the pathophysiology of migraine. Hyperalgesia is a key feature of migraine, and accumulating evidence indicates that electroacupuncture (EA) at the single acupuncture point (Fengchi [GB20]) is effective in ameliorating hyperalgesia. In clinical practice, multiple acupuncture points are widely used, especially GB20 and Yanglingquan (GB34). However, the role played by vasoactive neurotransmitters in acupuncture antihyperalgesic effect at the single or multiple acupuncture points remains unknown. We aimed to determine whether EA would exert its antihyperalgesic effects by modulating vasoactive neurotransmitter release from the perivascular nerves. Furthermore, we examined whether targeting multiple acupuncture points would be more effective than targeting a single point in reducing hyperalgesia. The mechanical and thermal hyperalgesia were evaluated by measuring the facial and hind-paw mechanical withdrawal thresholds, tail-flick and hot-plate latencies. Plasma concentrations of vasoactive neurotransmitters were determined using rat-specific ELISA kits from jugular vein, including calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), pituitary adenylate cyclase-activating polypeptide (PACAP), nitric oxide (NO), and endothelin-1 (ET-1). The result suggested that EA significantly ameliorated the mechanical and thermal hyperalgesia, reduced c-Fos levels in the trigeminal ganglion, and attenuated plasma and dural levels of vasoactive neurotransmitters, especially in the multiple acupuncture points group (GB20+GB34). In conclusion, EA exerts antihyperalgesic effect in a rat model of conscious recurrent migraine, possibly via modulation of the vasoactive neurotransmitters. Furthermore, targeting multiple acupuncture points is more effective than targeting a single point in reducing hyperalgesia.

Highlights

  • Migraine is a perplexing, essentially inherited, and variable disorder of brain function that affects one in nine adults worldwide [1, 2]

  • We investigated whether EA would alleviate the gradual reductions in mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT) following dural electrical stimulations (DES), and whether EA at multiple acupuncture points would be more effective at attenuating hyperalgesia than EA at a single point

  • No significant differences in tail-flick or hot-plate latencies were observed between the Non-Acu and Model groups at any time point (all P>0.05; Figures 2(c) and 2(d)). These findings indicated that EA attenuated hyperalgesia in rats following DES, and that the therapeutic effects of EA stimulation at GB20+GB34 are superior those observed for EA at a single point (GB20 or GB34)

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Summary

Introduction

Essentially inherited, and variable disorder of brain function that affects one in nine adults worldwide [1, 2]. Plasma neuropeptide Y (NPY) [17] and endothelin-1 (ET-1) level [18] are significantly increased relative to the levels in healthy individuals, while during the headache-free periods, the ET-1 level is significantly increased relative to the level in healthy individuals [18] and the plasma NPY level [19] is not significantly altered These vasoconstrictive neurotransmitters are important for regulating the peripheral and central circulation [20], leading to activation and sensitization of the trigeminovascular system (TS) (Figure 1(a)) [21,22,23]

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