Acupuncture For Functional Dyspepsia At Acupoints On Involved Meridian: A Multi-center, Randomized, Controlled Trial And A PET-CT Study

Aim:To evaluate the clinical efficacy and explore the central mechanism of puncturing at the acupoints on the involved meridian for Functional Dyspepsia patients.Methods:1. Multi-center, randomized and controlled trial was designed.354 patients who matched the inclusion criteria were randomly divided into 3 groups. Each group was administered puncturing at different ponints:Group A:acupoints on the involved meridian (ST34, ST36, ST40 and ST42); Group B:acupoints on the non-involved meridian (GB34, GB36, GB37and GB40), and Group C at four non-acupoints. Electroacupuncture with HAN's acupoint nerve stimulator was used at these points respectively once per day and totally for 20 days. The Nepean Dyspepsia Index (NDI) and Dyspepsic Symptom Score were used to evaluate the clinical efficacy after 10 days' and 20 days'treatment,4 weeks follow-up and 12 weeks follow-up.2. Brain fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) was performed on 32 FD patients and 12 healthy subjects (HS) in resting state. The characteristics of resting-brain activities in FD patients were obtained by comparing the cerebral glycometabolisms in FD patients with those in HS, the cerebral glycometabolisms in the milder FD patients and those in the relatively severer FD patients using Statistical Parametric Mapping software (SPM5.0), and analyzing the correlation between the changes in cerebral glycometabolism and the NDI scores of FD patients.18F-FDG PET-CT was performed on FD patients in Group A, B and C after 20 days'treatment. The characteristics of cerebral responses to puncturing at the acupoints on the involved meridian were obtained by comparing the changes in cerebral glycometabolism of the FD patients in Group A after acupuncture treatment with those of the FD patients in Group B and Group C.Results:1. The clinical efficacy of puncturing at the acupoints on the involved meridian1) The baselines of the three groups showed no statistical differences (p>0.05) 2) Although the NDI scores for Group A, Group B and Group C were all significantly improved after the treatment (p<0.01), only the improvements in Group A at all four assessment times were clinically significant, with an increase of more than 10 points on the NDI total scores. The changes in the NDI scores of Group A very significantly differed from those of Group B and Group C at all four assessment times (p＜0.01)3) The Dyspepsic Symptom Scoreson the four main symptoms for Group A were all significantly improved after the treatment (p<0.05). The improvements on postprandial fullness, early satiation and pigastric pain in Group A were significant better than those in Group B and Group C (p<0.05)4) There was significant difference between the three groups in the overall efficacy at the end of treatment (p<0.01).2. The characters of resting-brain activities in FD patients1) The difference in cerebrl activities between FD patients and HS:Compared to the HS, the FD patients showed increased glycometabolism in Insula (Brodmman area 13, BA13), Cingulate Cortex (BA24.31,32,30), Parahippocampal Gyrus (BA35), Caudate, Claustrum, Lentiform Nucleus, Thalamus, Hippocampus, Hypothalamus, Amygdala, Cerebellum, Frontal Cortex (BA3,4,8,9,10,11,47), Temporal Cortex (BA20,21,39,41), Parietal Lobe (BA7,40,43.39) and Occipital Lobe (BA23,37.19) (p<0.001);2) The key regions which might be closely relate to the pathology of FD:the activations in Middle Cingulate Cortex (MCC), Cerebellum, Thalamus, Anterior Cingulate Cortex (ACC) and Insula showed a very significant negative correlation with the NDI scores (p<0.01):the activations in MCC, Thalamus, ACC, Insula and cerebullum of the relatively severer patients significantly differ from those of the milder patients (p<0.005).3. The influence of different acupuncture methods on the resting-brain activities in FD patients1) The abnormally high cerebral glycometabolism of FD patients in Group A were all decreased significently after acupuncture treatment at Insula (BA 13), Cingulate Cortex (BA 24,31,32,29), Parahippocampal Gyrus (BA35), Caudate, Claustrum, Lentiform Nucleus, Thalamus, Hippocampus, Hypothalamus, Amygdala, Cerebellum, Frontal Lobe (BA 3,6,8,9,11,45,47), Temporal Lobe (BA19,21,22,37), Parietal Lobe (BA7,40,23,.39) and Occipital Lobe (BA 19) (p<0.005); The abonormally high cerebral glycometabolism of FD patients in Group B were slightly decreased after acupuncture treatment at left ACC (BA24), Posterior Cingulate Cortex (PCC, BA31), Lentiform Nucleus, Hippocampus Fusiform Gyrus (BA 37) and Inferior Temporal Gyrus (BA20), bilateral Thalamus and Cerebellum Tonsil (p<0.005); The abonormally increased cerebral glycometabolism of FD patients were partly decreased after acupuncture treatment of Group B including right MCC (BA23), left Middle Frontal Gyrus (BA6), bilateral PCC (BA23), Thalamus, Precuneus (BA30), Lingual Gyrus (BA17), Precentral Gyrus (BA6) and Cerebellum (p<0.005)2) All the key regions which might closely related to the pathology of FD including MCC, Cerebellum, Thalamus, ACC and Insula all showed significantly signal decrease after acupuncture treatment of Group A (p<0.05); only left ACC showed a signal decrease after acupuncture treatment of Group B (p<0.05); only right MCC and Thalamus showed signal decrease after acupuncture treatment of Group C (p<0.05)Conclusions:1. The clinical efficacy of puncturing are better at the acupoints on the involved meridian (Group A) for FD than at the acupoints on the non-involved meridian (Group B) and at non-acupoints (Group C).2. There are significant differences in resting brain activities between FD patients and HS. The general hyperactivities in cerebral-limbic system should be the main characteristic of the brain activities in FD patients. ACC, Insula, Thalamus, Cerebellum and MCC might be the core regions that closely relate to the pathogenesis of FD.3. The cerebral response to puncture at the acupoints on the involved meridian for FD might be characterized by inducing the co-operation of cerebrum and limbic system and regulating the functions of the FD-related key regions.