Changes in brain connectivity linked to multisensory processing of pain modulation in migraine with acupuncture treatment.

Migraine without aura (MWoA) is a major neurological disorder with unsatisfactory adherence to current medications. Acupuncture has emerged as a promising method for treating MWoA. However, the brain mechanism underlying acupuncture is yet unclear. The present study aimed to examine the effects of acupuncture in regulating brain connectivity of the key regions in pain modulation. In this study, MWoA patients were recruited and randomly assigned to 4 weeks of real or sham acupuncture. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. A modern neuroimaging literature meta-analysis of 515 fMRI studies was conducted to identify pain modulation-related key regions as regions of interest (ROIs). Seed-to-voxel resting state-functional connectivity (rsFC) method and repeated-measures two-way analysis of variance were conducted to determine the interaction effects between the two groups and time (baseline and post-treatment). The changes in rsFC were evaluated between baseline and post-treatment in real and sham acupuncture groups, respectively. Clinical data at baseline and post-treatment were also recorded in order to determine between-group differences in clinical outcomes as well as correlations between rsFC changes and clinical effects. 40 subjects were involved in the final analysis. The current study demonstrated significant improvement in real acupuncture vs sham acupuncture on headache severity (monthly migraine days), headache impact (6-item Headache Impact Test), and health-related quality of life (Migraine-Specific Quality of Life Questionnaire). Five pain modulation-related key regions, including the right amygdala (AMYG), left insula (INS), left medial orbital superior frontal gyrus (PFCventmed), left middle occipital gyrus (MOG), and right middle cingulate cortex (MCC), were selected based on the meta-analysis on brain imaging studies. This study found that 1) after acupuncture treatment, migraine patients of the real acupuncture group showed significantly enhanced connectivity in the right AMYG/MCC-left MTG and the right MCC-right superior temporal gyrus (STG) compared to that of the sham acupuncture group; 2) negative correlations were established between clinical effects and increased rsFC in the right AMYG/MCC-left MTG; 3) baseline right AMYG-left MTG rsFC predicts monthly migraine days reduction after treatment. The current results suggested that acupuncture may concurrently regulate the rsFC of two pain modulation regions in the AMYG and MCC. MTG and STG may be the key nodes linked to multisensory processing of pain modulation in migraine with acupuncture treatment. These findings highlighted the potential of acupuncture for migraine management and the mechanisms underlying the modulation effects.

Acupuncture for menstruation-related migraine prophylaxis: A multicenter randomized controlled trial.

Objective: The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM). Patients and methods: This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1-3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1-3 and 4-6. Results: A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17-0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82-1.07) in the acupuncture group and 0.61 (95% CI, 0.50-0.71) in the medication group over cycles 1-3. Conclusion: This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles. Clinical trial registration: [https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606].

Determining 5HT7R's Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine.

Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT7 receptor (5-HT7R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT7R could influence phosphorylation of protein kinase A (PKA)- or extracellular signal-regulated kinase1 / 2 (ERK1 / 2)-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT7R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK1 / 2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 min every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT7R antagonist (SB269970) or 5-HT7R agonist (AS19) was administered intrathecally before each IS application at 2-day intervals during the 7-day injection protocol. The changes in 5-HT7R and 5-HT7R-associated signaling pathway were examined by real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) analyses. When compared with IS group, mechanical and thermal pain thresholds of the IS + EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT7R mRNA expression and protein levels were detected in the IS + EA group. More importantly, 5-HT7R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK1 / 2. Injecting 5-HT7R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK1 / 2. Our findings indicate that 5-HT7R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK1 / 2 in TG and TNC.