Electroacupuncture Inhibits Hyperalgesia by Alleviating Inflammatory Factors in a Rat Model of Migraine

Abstract

Objective: Acupuncture has a therapeutic effect similar to that of prophylactic drugs and can be considered a treatment option for migraineurs. However, the mechanism of acupuncture treatment's effect on migraine is uncertain. An approach based on anti-inflammatory effects is an important treatment strategy for migraine because non-steroidal anti-inflammatory drugs (NSAIDs) are usually used during migraine attacks. Meningeal inflammation is thought to be responsible for the activation of the trigeminovascular system. Our previous study found that electroacupuncture (EA) decreased neurogenic inflammation mediator expression in the trigeminal ganglion (TG) and alleviated hyperalgesia. The present study examined whether EA would inhibit hyperalgesia by alleviating neurogenic inflammatory factors.

Methods: A rat model of migraine was established using dural electrical stimulation (DES). Five groups were analyzed in this study. The Model group received DES three times to mimic migraine attacks, a Control group had sham DES, and three groups received electroacupuncture after DES: a Non-Acu group at a non-acupuncture point, a GB20 group at GB20, and a GB20/34 group at GB20 and GB34 acupuncture points. We evaluated mechanical hyperalgesia using an electronic von Frey esthesiometer in the awake state. After sacrifice, the dura mater was analyzed using immunofluorescence. Serum calcitonin gene-related peptide, cyclooxygenase-2, brain-derived neurotrophic factor, IL-1β, IL-6, and TNF levels were determined using enzyme-linked immunosorbent assays to evaluate the anti-inflammatory effect of acupuncture.

Results: After repeated DES, we observed facial and hind paw mechanical hyperalgesia, which was inhibited by electroacupuncture. Electrical stimulation increased the number of mast cells and macrophages and serum levels of inflammatory factors. GB20 and GB20/34 electroacupuncture significantly decreased the number of mast cells and macrophages and serum levels of inflammatory factors. Moreover, electroacupuncture at GB20/34 was superior to that at GB20 alone in inhibiting hyperalgesia and alleviating inflammatory factors.

Conclusion: Electroacupuncture inhibits DES-induced hyperalgesia by alleviating inflammatory factors. Inhibition of dural mast cells, macrophages, and serum inflammatory factors may be one of the mechanisms involved in acupuncture treatment's effect on migraine.

Keywords: GB20; GB34; acupuncture; hyperalgesia; inflammatory; migraine; neurogenic inflammation.

Figure 1

Diagram of the experimental protocol.

Figure 2

Diagram of the acupuncture points used in the GB20 group (A) and GB20/34 (B) group in a rat.

Figure 3

Electroacupuncture (EA) treatment alleviated impairments in the mechanical withdrawal thresholds of the face (A) and hind-paw (B) in rats subjected to dural electrical stimulation. Data are presented as the mean ± standard deviation, n=10/group; Model group vs Control group (**P<0.01, *** P<0.001), GB20, GB20/34 group vs Model group (#P<0.05, ## P<0.01), GB20 group vs GB20/34 group(^P<0.05).

Figure 4

Electroacupuncture (EA) treatment decreased the number of dural mast cells. Scale bar = 50 μm. Model group vs Control group (*P<0.05), GB20, GB20/34 group vs Model group (##P<0.01).

Figure 5

Electroacupuncture (EA) treatment decreased the number of dural macrophages. Scale bar = 50 μm. Model group vs Control group (***P<0.001), GB20, GB20/34 group vs Model group (##P<0.01).

Figure 6

Electroacupuncture (EA) decreased serum levels of neuropeptide and inflammatory factors. Model group vs Control group (***P<0.001), GB20, GB20/34 group vs Model group (#P<0.05, ##P<0.01, ###P<0.001), GB20 group vs GB20/34 group (^P<0.05).