| Objective:In this study,a clinical randomized controlled trial was conducted for evaluating the effectiveness of treating chronic tension-type headache(CTTH)with acupuncture deqi.Additionally,the RNA sequence technology was used to explore differentially expressed genes(DEGs),attempting to find out the potential pathogenesis of CTTH and mechanism of acupuncture deqi.Methods:1.Clinical TrialIn this randomized controlled trial,111 CTTH subjects were randomly assigned to deep needling group(DG)and superficial needling group(SG).Participants received 20 sessions of acupuncture treatments over 8 weeks.The whole study period was 36 weeks,of which the baseline period was 4 weeks,the treatment period was 8 weeks,and the follow-up period was 24 weeks.The main outcome measures were the proportion of responders within 4 weeks assessed at week 16 after randomization.The secondary outcomes included the number of headache days,the mean intensity and the mean duration of headache attacks in 4 weeks.The above outcomes were evaluated every 4 weeks from the baseline to the end of the follow-up period.And the main observation time point was week 16 after randomization.In addition,the Massachusetts General Hospital Acupuncture Sensation Scale(MASS)was applied to record deqi sensations of participants.2.Analysis of Differentially Expressed GenesFive CTTH patients with relatively strong deqi sensation in the DG,5 CTTH patients with relatively weak deqi sensation in the SG,and 5 healthy participants were included in this part.The venous blood samples were collected from healthy participants and CTTH patients before and after treatment.The total RNAs were extracted and purified,and the gene expression profiles of the samples were sequenced by BGISEQ-500 platform.DEGs were screened out from the gene expression profiles.The function of DEGs were annotate with Gene Ontology(GO)and the functional enrichments of pathways related to DEGs were analyzed with the Kyoto Encyclopedia of Genes and Genomes(KEGG).Results:1.Clinical Trial(1)The Clinical Effectiveness of Deep and Superfical Needling GroupsThe baselines of two groups were balanced and comparable(p>0.05).The proportions of responders in DG were higher and the numbers of headache days within 4 weeks of DG were less than those of SG at each observation time points during week 4 to 32(p<0.05).Additionally,the average durations of headache attacks of DG were shorter than the SG in week 24~28(p<0.05).However,the differences of mean intensities of headache attacks between two groups were not statistically significant(p>0.05).(2)The Evaluation of Deqi Sensation in Deep and Superfical Needling GroupsThe frequencies of fullness/distension and deep pressure sensations in DG were higher than SG(p<0.01),and the frequency of tingling sensation in DG was lower than SG(p<0.01).The MASS index and the intensity of fullness/distension were significantly higher and the intensity of tingling was much lower of DG than those of SG(p<0.01).(3)The Impact Factors of DeqiAccording to screening and validating of various potential factors,deqi sensation was only associated with deep and superficial needling methods of this trial.Compared with SG,the deqi intensity was much stronger,especially fullness/distention sensation(p<0.001).(4)The Correlation Between Clinical Effectiveness and Deqi SensationAt the main observation time point,MI and fullness/distention were positively correlated with the proportion of responders and the number of headache days(p<0.05).Fullness/distention sensation had a positive effect on reducing the mean intensity of headache attacks(p<0.05).In addition,soreness sensation was positive related to shortening the average duration of headache attacks(p<0.05),but tingling sensation was just the opposite(p<0.05).2.Analysis of Differentially Expressed Genes(1)Compared with the healthy subjects,there were 327 differentially expressed genes in CTTH patients.A total of 41 differentially expressed genes were related to the mechanism of acupuncture with strong deqi sensation,and 18 were related to acupuncture with weak deqi sensation.(2)The result of GO functional annotation suggested that differentially expressed genes of CTTH were mainly involved in signal transduction,chemotaxis,cell communication,cell adhesion,cell membrane composition.And the functions of DEGs in acupuncture with strong deqi mechanism were related to cytokine mediated signaling pathway.(3)KEGG signal pathway analysis showed that the DEGs between healthy subjects and CTTH patients were significantly enriched to 13 pathways,and the DEGs of CTTH before and after acupuncture with relatively strong deqi sensation were significantly enriched to 18 pathways.There was only one common pathway named cell adhesion molecules(CAMs).In addition,MTPN,CNTNAP3,CNTNAP3 B and CD274 might play important parts in effectivenss of treating CTTH with acupuncture deqi.Conclusion:1.The effectiveness of the deep needling group might be superior to the superficial needing group,especially in reducing headache days.2.Acupuncture at different depths in this trial was an important factor for inducing different deqi sensation.Compared with superficial needling,deep needling was more likely to induce stronger deqi sensation with the nature of fullness/distention.3.Deqi might be a key factor affecting the therapeutic effect of treating CTTH with acupuncture.In reducing headache days and relieving headache intensity,relatively strong deqi and sensation of fullness/distention in nature had superior effects.In shortening duration of headache attacks,deqi sensation of soreness in nature had relatively good effects.4.Acupuncture deqi might have an affect on the gene expression profiles of CTTH patients.The molecular biological mechanism of treating CTTH with acupuncture deqi might be related to the regulation of MTPN,CNTNAP3,CNTNAP3 B and CD274. |
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