Acupuncture Modulates Acute Low Back Pain In The Brain Networks:an FMRI Study

ObjectiveLow back pain is the most common clinical pain and affects80-85%of people over their lifetime. Unlike infectious and cardiovascular diseases or cancer, low back pain is rarely fatal. However, this pain is often acute attack or aggravation, and lead to serious social and economic burden to patients, including activity limitation, as well as broader impacts such as participation restrictions, care burden, use of health-care resources and financial burden. Furthermore, this disease has become the most frequent activity-limiting complaint and the second leading cause of sick leave in the young and middle aged.Because of its simple, economic and fewer adverse side effects for treating this pain, acupuncture as one unique Traditional Chinese Medicine method, got the increasingly widespread concern at home and abroad. In1997, the United States National Institutes of Health held a hearing on acupuncture and reached a consensus that acupuncture can be used as an adjunct therapy on low back pain. While traditional acupuncture for low back pain have a significant effect, brain mechanism of acupuncture for acute low back pain has been limited due to the lack of an effective non-invasive research tools and acute attack of the disease. In recent years, non-invasive, high spatial and temporal resolution of functional brain imaging techniques, including functional magnetic resonance imaging (fMRI) and positron emission computerized tomography (PET), have quickly development which greatly promoted for this mechanism study.To data, numerous fMRI studies have greatly contributed to our understanding of the analgesic mechanism of acupuncture by using experimental heat pain on limbs, however, only a few have examined clinical pain, with the least focus on ALBP. Firstly, the researchers found that experimental pain stimulus widely deactivates the default mode network (DMN), and activates the following brain areas:insula and S2, anterior cingulate cortex (ACC), thalamus, S1, prefrontal and posterior parietal cortices, striatum, cerebellum, periaqueductal grey (PAG) and supplementary motor area (SMA). Secondly, as subjects under painless condition, acupuncture produced more activation in regions associated with cognitive and emotional cortical regions (dmPFC and d1PFC), and less deactivation in DMN and sensorimotor regions (SI, SII, insula) compared with non-insertive cutaneous stimulation. However, others demonstrated that acupuncture yielded more deactivation in limbic regions, including DMN, and less activation in sensorimotor and attention-related regions compared with cutaneous stimulation. Consequently, it is foreseeable that acupuncture treatment in experimental ALBP subjects can lead to more sophisticated fMRI signal changes in these brain networks.MethodsA total of15right-handed subjects were enrolled in this study. They were informed to accept two different ways acupuncture, and needed to pay attention to de-qi sensation during needling.ALBP model was prepared in the muscle of right lower back using a method modified from previous studies,20min before anatomic scanning. At first, we located this model2cm lateral to the spinous process at the level of the4th lumbar vertebra. Then, we vertically inserted an in-dwelling needle (24gauge), which attached to a long connecting tube of a computer-controlled power injector (Spectris Solaris EP, Medrad, Inc., Warrendale, PA, USA) and filled with sterile hypertonic saline (1mL,5%), into the above location at a depth of1.5cm. In this experiment, hypertonic saline was injected intramuscularly from the computer-controlled power injector in order to produce a persistent painful ALBP. The injection included a bolus injection (0.1mL within5s), which was followed by a continuous injection (0.15mL/min). Notably, we had previously examined the effects of different doses (0.1mL/min,0.15mL/min,0.2mL/min) of this sterile hypertonic solution in the preliminary experiment and found that0.15mL/min was most suitable for our experiment because it induced moderate-high experimental ALBP.Experimental procedures:At first, anatomic MRI scanning was performed as each subject lay still in the Philips3.0T Achieva scanner (Royal Philips Electronics, Eindhoven, The Netherlands) with ears and eyes closed. Next, two functional scans were randomly obtained for each subject, one during ACUP and one under SHAM condition. Each condition comprised a block design, with three30-s stimulation blocks (ON block) interspersed between three30-s baseline blocks (OFF block). During three ON blocks, therapeutic stimulation (ACUP or SHAM) was administered at BL40by an experienced acupuncturist. The time for each functional scan was3min, and the time interval between the two functional scans was set to20min in order to maximize washout of the sustained effects the former stimulation.ACUP was administered by inserting a non-magnetic (pure silver),0.4-mm-diameter,60-mm-long acupuncture needle (Beijing Zhongyan Taihe Medicine Co., Ltd, Beijing, China) vertically into BL40at a depth of approximately2cm. After adjusting the needle in order to obtain a subjective acupuncture sensation, or de-qi sensation, the needle was manually twirled (±180°) at1Hz with "even reinforcing and reducing" needle manipulation in traditional Chinese medicine. SHAM was delivered by a von Frey monofilament. An acupuncturist poked this monofilament through a needle-guide tube and tapped it gently over the skin of the BL40with the same rate as that used during ACUP.Considering that SHAM may cause subjective bias towards the stimulation, all subjects were purposely misguided that they would receive different forms of acupuncture, and only needed to concentrate on the degree of lower back pain as well as the acupuncture sensations of BL40. Moreover, subjects were asked to keep their eyes and ears closed in order to prevent them from discriminating the therapeutic stimulation. Therefore, the SHAM condition was assumed to minimize not only the superficial and cutaneous somatosensory effects around BL40but also the cognitive processing induced by the subjects expectations of ACUP.Psychophysical data collection and analysis:Before and after each functional scan, subjects were required to rate the intensity of pre-and post-treatment lower back pain and acupuncture sensations (soreness, numbness, heaviness, fullness), using a10-point visual analogue scale (0=none,1-3=mild,4-6=moderate,7-9=strong and10=unbearable). In this study, the change score (pre-minus post-treatment) of the lower back pain and acupuncture sensations were compared between stimulation groups using Wilcoxon signed-rank test, significant at P<0.05(SPSS13.0, IBM Corporation, NY, USA).Imaging data collection and analysis:Structural and functional scans were acquired with a3.0T Philips Achieva MRI System (Royal Philips Electronics, Eindhoven, The Netherlands) with an8-channel head array coil equipped for echo planar imaging. The images were axial and parallel to the anterior commissure-posterior commissure line, which covered the whole brain. Structural images were collected prior to functional imaging using a T1-weighted fast spin echo sequence [repetition time (TR)/echo time (TE)=500/14ms, flip angle=90°,0.859mm×0.859mm in-plane resolution, slice thickness=1mm]. Blood oxygenation level-dependent functional imaging was acquired using a T2*-weighted, single-shot, gradient-recalled echo planar imaging sequence (TR/TE=2000/40ms, flip angle=90°,3.4mm×3.4mm in-plane resolution,90time points for a total of180seconds). In addition, fMRI image collection was preceded by5dummy scans to minimize gradient distortion.Data analysis was performed with SPM8software (http://www.fil.ion.cl.ac. uk/spm/), which comprised pre-processing, first-level analysis and second-level analysis in order. Pre-processing includes motion correction, slice-timing correction, normalization to the Montreal Neurological Institute standard brain (MNI152) and spatial smoothing with a Gaussian kernel of full width at half maximum of8mm. For motion correction, if translation or rotation of the subject’s head movements was more than1.5mm or1.5°, that subject’s data was excluded. In first-level analysis, the pre-processing functional data was modelled using a general linear model. Explanatory variables, including the stimulation task (ACUP or SHAM) and baseline, were modelled using a boxcar function convolved with the canonical hemodynamic response function in SPM8. After that, parameter estimates were assessed with least square regression analyses. Then, statistical parametric maps of the stimulation task minus the baseline contrast were collected at each voxel for each subject. In second-level analysis, a one-sample t-test was used for ON (ACUP or SHAM) minus OFF, and a paired t-test was applied for ACUP minus SHAM to assess difference between the ACUP and SHAM conditions.All statistical maps were corrected for multiple comparisons at the cluster level (P=0.005, derived from an uncorrected P=0.005on the voxel level), with a minimum cluster extent of31contiguous voxels as estimated by the AlphaSim application (http://afni.nimh.nih.gov/afni/doc/manual/AlphaSim).ResultsSubjects and psychophysical responses:There were significant differences between the ACUP and SHAM groups in the change score of the lower back pain (p=0.043), soreness (p=0.014), dull pain (p=0.029) and fullness (p=0.001). fMRI results:Compared with SHAM, ACUP evoked more significant decreases in fMRI signals in a large number of brain regions. These deactivated regions included sensorimotor regions (left SMA and bilateral frontal eye field), attention-related regions (right dlPFC and bilateral pMCC), limbic regions (left PAQ right ventral tegmental area, bilateral pregenual ACC, dmPFC, middle cingulate cortex, precuneus, retrosplenial cingulate cortex, posterior cingulate cortex, parahippocampus, hippocampus, thalamus, mammillary body, red nucleus and substantia nigra, right supramarginal gyrus and angular gyrus, bilateral cerebellar anterior lobe and lateral occipital gyrus. However, only one activated cluster namely the right insula/M1was found.Compared with baseline, ACUP yielded significant deactivation in the sensorimotor regions (left M1, S2and frontal eye field), limbic regions [left insula, mammillary body, right hippocampus, bilateral dorsomedial prefrontal cortex (dmPFC), pregenual ACC, PAQ thalamus and parahippocampus], right supramarginal gyrus, angular gyrus and lateral temporal cortex. Besides deactivation, ACUP also evoked activation in the sensorimotor regions (right M1and S1and bilateral SMA), attention-related regions [bilateral dorsolateral prefrontal cortex (dlPFC) and posterior midcingulate cortex (pMCC)], limbic regions (right insula, bilateral frontopolar area and pMCC), right supramarginal gyrus and frontal operculum cortex. The total number of activated voxels was more than twice that of deactivated voxels. Furthermore, the deactivated voxels in the ACUP group were symmetrical, while the activated voxels were mainly concentrated around the right insula.Compared with baseline, SHAM only produced one significant deactivated cluster, namely the left insula/frontal operculum/M1. However, SHAM induced widespread activation in the sensorimotor regions (right frontal eye field and bilateral SMA), attention-related regions (bilateral dlPFC), limbic regions (right frontopolar area, bilateral orbitofrontal cortex, precuneus, retrosplenial cingulate cortex, posterior cingulate cortex, pMCC, parahippocampus, hippocampus, uncus, lateral temporal cortex, temporal pole, thalamus, amygdala, mammillary body, PAG, red nucleus and substantia nigra), bilateral supramarginal gyrus, angular gyrus, cerebellum anterior lobe and lateral occipital gyrus. In contrast to the small gap between activation and deactivation with ACUP, SHAM induced more numerous and intense activated voxels than deactivated ones. In addition, there were more activated voxels on the right side than on the left, and these were presumably symmetrical in the brain.ConclusionAfter ACUP and SHAM treating acute back pain, there is a statistically significant difference in the number, strength, nature and distribution of brain regions. Acupuncture treatment for acute back pain changed multiple functional brain networks, in which the analgesic and emotion-related regions of limbic system (anterior cingulate cortex, anterior mid-cingulate gyrus, dorsal medial prefrontal), and memory-related brain regions (default network and mammillary body) is particularly significant. Our study suggested that acupuncture stimulation goes beyond somatosensory-guided mind-body therapy for ALBP.