• Users Online: 1825
  • Home
  • Print this page
  • Email this page

 Table of Contents  
RESEARCH ARTICLE
Year : 2021  |  Volume : 16  |  Issue : 2  |  Page : 388-393

Brain plasticity after peripheral nerve injury treatment with massage therapy based on resting-state functional magnetic resonance imaging


1 School of Rehabilitation Science; Department of Rehabilitation Medicine, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
2 Department of Traumatology and Orthopedics, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
3 Department of Traumatology and Orthopedics, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine; Yangzi Rehabilitation Hospital, Tongji University, Shanghai, China
4 School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China

Date of Submission04-Mar-2020
Date of Decision17-Mar-2020
Date of Acceptance16-Apr-2020
Date of Web Publication24-Aug-2020

Correspondence Address:
Jian-Guang Xu
School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai
China
Login to access the Email id

Source of Support: This study was supported by National Key R&D Program of China, No. 2018YFC2001600 (to JGX); and Shanghai Science and Technology Committee of China, Nos. 18511108300 (to JGX), 18441903800 (to MXZ) and 18441903900 (to XYH), Conflict of Interest: None


DOI: 10.4103/1673-5374.290912

Rights and Permissions
  Abstract 

Massage therapy is an alternative treatment for chronic pain that is potentially related to brain plasticity. However, the underlying mechanism remains unclear. We established a peripheral nerve injury model in rats by unilateral sciatic nerve transection and direct anastomosis. The experimental rats were treated over the gastrocnemius muscle of the affected hindlimb with a customized massage instrument (0.45 N, 120 times/min, 10 minutes daily, for 4 successive weeks). Resting-state functional magnetic resonance imaging revealed that compared with control rats, the amplitude of low-frequency fluctuations in the sensorimotor cortex contralateral to the affected limb was significantly lower after sciatic nerve transection. However, amplitudes were significantly higher in the massage group than in a sham-massage group. These findings suggest that massage therapy facilitated adaptive change in the somatosensory cortex that led to the recovery of peripheral nerve injury and repair. This study was approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine of China (approval No. 201701001) on January 12, 2017.

Keywords: injury; massage; model; neuron; peripheral nerve; plasticity; rat; repair


How to cite this article:
Xing XX, Zheng MX, Hua XY, Ma SJ, Ma ZZ, Xu JG. Brain plasticity after peripheral nerve injury treatment with massage therapy based on resting-state functional magnetic resonance imaging. Neural Regen Res 2021;16:388-93

How to cite this URL:
Xing XX, Zheng MX, Hua XY, Ma SJ, Ma ZZ, Xu JG. Brain plasticity after peripheral nerve injury treatment with massage therapy based on resting-state functional magnetic resonance imaging. Neural Regen Res [serial online] 2021 [cited 2020 Sep 27];16:388-93. Available from: http://www.nrronline.org/text.asp?2021/16/2/388/290912

Xiang-Xin Xing, Mou-Xiong Zheng, Xu-Yun Hua. These authors contributed equally to this work.
Chinese Library Classification No. R459.9; R741; R244.1



  Introduction Top


Peripheral nerve injury (PNI) results in damaged axons and loss of sensory, motor, and autonomic functions, which can lead to a decline in the quality of life. Surgical repair is the primary treatment for PNI (Sullivan et al., 2016). Although recent years have seen great advances in microsurgery techniques and neural regeneration-promoting methods, functional recovery following reinnervation is still less than satisfying (Miller, 2017; Neumann et al., 2019). Accumulating evidence suggests that brain plasticity-based rehabilitation is essential for the restoration of function in these cases (Sampaio-Baptista et al., 2018). Massage therapy is a popular non-drug intervention that uses mechanical force directly on the human body to alleviate discomfort and promote health (Chou and Huflman, 2007; Dabbour et al., 2018). Massage has been proven to be effective in many clinical trials. For example, perineal massage performed during pregnancy significantly decreased perineal trauma at birth (Labrecque et al., 2001). In other studies, massage reduced the intensity of muscle soreness after exercise-induced muscle damage, and decreased cancer-related fatigue for cancer survivors (Kinkead et al., 2018). Meanwhile, massage has important and beneficial effects on neurological diseases. Massage has been reported to trigger parasympathetic nervous system activation (and suppress sympathetic nervous system activity) by stimulating skin sensors dominated by vagal nerve fibers, which can improve the neurobehavioral outcome in infants (Diego and Field, 2009). Field et al. (2014) found applying massage therapy to the tender points in patients with carpal tunnel syndrome effectively reduced pain and increased the range of motion of the affected limb. Additionally, Aboodarda et al. (2018) demonstrated that rolling massage could reduce the central excitability of neuronal circuits that innervate the knee extensors. Andrzejewski et al. (2014) reported that the tendons of rats in a massage group exhibited higher expression of proteins important for regulating tendon structure (vascular endothelial growth factor-A, fibroblast growth factor-2, and CD34) than was observed in other groups. Furthermore, Zhang et al. (2019) found that massage therapy changed the status of DNA hydroxymethylation, which can regulate the expression of neurodevelopment-related genes. Most massage-related research has generally focused on the injured region.

We also found that massage therapy facilitated nerve regeneration following sciatic nerve transection and repair in rats, and the model was a typical PNI model that allows the evaluation of neuropathic changes and nerve regeneration (Casals-Díaz et al., 2009; Chawla et al., 2014). According to our previous study (Ma et al., 2016), we confirmed that massage can promote the proliferation of muscle satellite cells, regulate the expression of related myogenic factors, accelerate the recovery of muscle fibers, improve the structure and morphology of skeletal muscle after sciatic nerve transection and repair, and delay the atrophy of skeletal muscle. Our conclusion was similar to that of Wang et al. (2019). In another study (Wu et al., 2018), cortical remodeling occurred in the same PNI-model rats, but these authors used a different intervention method to us. We inferred (hypothesized) that massage therapy might also cause neuroplastic alterations in the brain, but our understanding of brain remodeling mechanisms after massage is still imperfect due to the limited literature.

By combining electro-neurophysiological recordings and functional magnetic resonance imaging (fMRI), studies have shown that low-frequency (0.01–0.08 Hz) fluctuations (LFF) in blood oxygenated-level-dependent (BOLD) fMRI signals are closely related to spontaneous neuronal activity (Logothetis et al., 2001; Goldman et al., 2002). Zang et al. (2007) developed the amplitude of LFFs (ALFF) index (the square root of the power spectrum integrated in a low-frequency range) for detecting the regional intensity of spontaneous fluctuations in the BOLD signal. The ALFF is considered a potentially meaningful index of the brain's energy and morphology (Aiello et al., 2015; Liao et al., 2019). Furthermore, the ALFF has been widely applied in functional neuroimaging with a slightly higher test-retest reliability and a higher specificity (Hoptman et al., 2010). Therefore, the ALFF can be used to evaluate the intensity of spontaneous neuronal activity in the brain (Zang et al., 2007). The present study aimed to test our hypothesis by using BOLD signals and the ALFF to measure brain activity associated with the effect of massage in PNI rats.


  Materials and Methods Top


Animals

Thirty-two healthy female clean-grade Sprague-Dawley rats aged 6–8 weeks and weighing 180–200 g were provided by Shanghai Slack Laboratory Animal Limited Liability Company (Shanghai, China) (license No. SCXK [Hu] 2012-0002). They were kept in a laboratory environment with a 12-hour light/dark cycle. The temperature was set to 20–22°C and rats were provided adequate food and water. The rats were acclimated to their cages for 7 days before beginning any intervention. This study was approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. 201701001) on January 12, 2017. All procedures and protocols were in accordance with the Guide for the Care and Use of Laboratory Animals described by the US National Institutes of Health and followed the Animal Research Reporting: In Vivo Experiments (arrive) guidelines.

PNI procedure

The rats were randomly divided into normal, model, sham-massage, and massage groups (n = 8 per group). In the model, sham-massage, and massage groups, PNI was established by sciatic nerve transection and direct anastomosis. The rats were anesthetized with intraperitoneal injection of pentobarbital sodium (40 mg/kg; Notlas Co., Ltd., Beijing, China) and placed on a clean operating table in the prone position. We shaved an area about 5 mm below the sciatic tubercle of the right hip and made an incision along the route of the sciatic nerve. While viewing under a 10× microscope (Shanghai Medical Optical Instruments Co., Ltd., Shanghai, China), the trunk of the right sciatic nerve was exposed and separated from the gluteal muscle. It was then transected with a razor blade 1 cm below the lower edge of the piriformis muscle. The epineurium of the sciatic nerve was then sutured with 11-0 sutures [Figure 1]A, [Figure 1]B, [Figure 1]C. The rats in the normal group were fed normally without surgery.
Figure 1: Demonstration of peripheral nerve transection, repair surgery, and massage therapy.
(A) Exposure of the right sciatic nerve. (B) Sciatic nerve transection. (C) Direct nerve repair by perineurial suturing. The yellow arrow indicates the nerve coaptation site. (D) Custom-made massage device. 1: Rubber strips; 2: electric motor; 3: pressure sensor; 4: tensor spring; 5: electric relay. (E) Massage therapy procedure. The rat was fixed on the holder with the gastrocnemius muscle of the affected hindlimb clamped by the two rubber strips of the massage simulator. (F) Schematic diagram of the massage therapy. The red arrows indicate the different directions of force produced by the instrument.


Click here to view


Massage and sham-massage intervention

Both massage and sham massage were performed 1 week after model establishment (Ma et al., 2016). Interventions lasted 10 minutes and were performed once a day for 4 weeks. The massage group was treated with a massage instrument (Chinese patent No. 2014204820753; [Figure 1]D). Rats in the sham-massage and massage groups were fixed on a holder and the right gastrocnemius muscle was clamped by the two rubber strips of the massage simulator. The massage group were treated by instrument massage (pressure = 0.45 N, frequency = 120 times/min, velocity = 1 cm/s; [Figure 1]E and [Figure 1]F). The sham-massage group did not receive any massage, but their right gastrocnemius muscles remained lightly clamped for 10 minutes. Normal and model groups did not receive any intervention.

fMRI image acquisition

All fMRI scans of the brain were performed 5 weeks after model establishment by a Bruker 7T magnetic resonance system (Bruker Corporation, Bremen, Germany) with a coil for small animals. After 2.5% isoflurane (RWD Life Science Co., Ltd., Shenzhen, China) induced anesthesia, rats were fixed on the scanner and given continuous 1.5–2% isoflurane anesthesia with ventilator support and respiratory monitoring. Interlayer-scanning echo-plane imaging parameters were as follows: flip angle = 90°, slice thickness = 0.5 mm, repetition time = 3000 ms, echo time = 20 ms, number of averages = 1, field of vision = 32 mm × 32 mm, matrix = 64 × 64 voxels. Image acquisition included 200 time points and lasted 200 × 3 seconds; in other words, the duration was 10 minutes.

fMRI data preprocessing

The resting-state fMRI data were preprocessed using the Statistical Parametric Mapping 12 (SPM 12) toolbox (Welcome Department of Cognitive Neurology, University College, London, UK; http://fil.ion.ucl.ac.uk.spm/) and the Resting-State fMRI Data Analysis Toolkit (REST) toolbox (http://www. restfmri.net) toolbox in Matlab version 2014a (MathWorks, Natick, MA, USA). First, we expanded the images by 10 × 10 × 10 times to match the size of the human brain—which made it possible to use/modify processing algorithms originally designed for human data—and stripped the none-brain manually (Gu et al., 2016; Peng et al., 2016). The amplified procedure only changed the dimension descriptor fields in the file header without interpolation. The first five volumes of each functional time series were discarded as the signals had not yet reached equilibrium. The preprocessing steps included slice timing correction, realignment for head motion, spatial normalization in Schwarz's standard space (resampling with 2.06 mm × 2.06 mm × 2 mm resolution) (Paxinos and Watson, 2005; Schwarz et al., 2006), spatial smoothing (using the Gaussian kernel with 4.12 mm × 4.12 mm × 4 mm full-width-at-half-magnitude). Regressing the nuisance signal, detrending, and filtering (0.01–0.08 Hz) were used on the time series of each voxel to reduce the influence of low-frequency drift (linear and quadratic), physiological high-frequency respiration, and noise. The images were then corrected for slice-timing and head movement. Rats with head motion greater than 1 mm in any direction or head rotations greater than 1° were excluded. BOLD signals detected by fMRI reflect changes in the activity of neurons (Hillman, 2014; Rogachov et al., 2016). The BOLD signal fluctuates, and the ALFF can tell us how much fluctuation is happening in a given brain region. We calculated ALFF values and standardized ALFF values (the ALFF value of each voxel divided by the global mean values). We then transformed the ALFF values to zALFF values with a Fisher r-to-z transformation, which allowed us to compare them among the groups (Yang et al., 2007).

Statistical analysis

We conducted a one-way analysis of variance of the zALFF values with Group as a factor (normal, model, sham massage, and massage). After the interaction effect analysis, a binary mask was generated using clusters of statistical significance. Further post hoc two-sample t-tests were then performed within this mask and p-values were corrected for multiple comparisons. The correction standard was determined by Monte Carlo simulations (individual voxel P-value = 0.001, 1000 simulations, full-width-at-half-magnitude = 4 mm, using the group GM mask) applied with the AlphaSim procedure in the REST toolbox. In this procedure, a corrected significance level of P < 0.05 was obtained for a minimum volume of 12 voxels. This process enabled identification of significant differences between each pair of groups.


  Results Top


Effect of massage therapy on the general condition of PNI rats

All rats survived after sciatic nerve transection and repair surgery. Reddening and swelling around the wound was only observed in three rats within the first post-PNI week (two in the massage group and one in the sham-massage group). The wound completely recovered in all rats without obvious infection. No rats needed to be replaced in this study.

One to three weeks following PNI, all rats in the model, sham-massage, and massage groups showed different degrees of muscle atrophy, limp gait, ankle joint stiffness, and limited metatarsal flexion in the affected limb. These syndromes had recovered to varying degrees after 4 weeks of intervention.

Massage therapy alters regional ALFF values in the resting-state brain of PNI rats

Regional changes in ALFF value were calculated in the resting-state by performing a whole brain cluster-wise comparison. Significant main effects of Group (F(3,28) = 14.85, P < 0.0001) were distributed in the left somatosensory cortex [Figure 2]. The significant clusters were extracted to generate a binary mask for post hoc analysis. The post hoc analysis revealed significantly lower ALFF values in the model group than in the normal group, specifically in bilateral somatosensory cortices, left parietal association cortex, and bilateral auditory cortices (P < 0.05). ALFF values in the massage group were significantly higher than those in the sham-massage group, specifically in bilateral somatosensory cortices (P < 0.05). Additionally, ALFF values in the mesencephalic region were significantly lower in the massage group than in the model group (P < 0.05; [Figure 3] and [Table 1]).
Figure 2: Main effects of massage on a peripheral nerve injury rat.
Regions of somatosensory cortex that differed in amplitude of low-frequency fluctuation value among the four groups (normal, model, sham massage, and massage groups). The red clusters in the left somatosensory cortex (blue area) were significantly different among the four groups located. The others red points did not pass the multiple comparison tests. The green numbers are coordinates referenced to a stereotaxic magnetic resonance imaging template of the rat brain.


Click here to view
Figure 3: Effects of massage on zALFF values in a peripheral nerve injury rat.
zALFF values in rat cortex were analyzed by one-way analysis of variance followed by post hoc two-sample t-test. Normal: Naïve rats without intervention; Model: right sciatic nerve transection and immediate repair; Sham massage: right sciatic nerve transection and repair and 4-week sham-massage intervention; Massage: right sciatic nerve transection and immediate repair and 4-week massage over the right gastrocnemius muscle. Values are expressed as the mean. Error bars are the SD. zALFF: Fisher's z transformation amplitude of low-frequency fluctuations.


Click here to view
Table 1: Comparison of amplitude of low-frequency fluctuation between pairs of groups following 4 weeks of intervention

Click here to view



  Discussion Top


The present study showed a significant difference among the four groups in the left somatosensory cortex. Further, the ALFF values in left somatosensory cortex were higher in the massage group than in the model or sham-massage groups. These results indicate that massage improves the restoration of local brain activity after peripheral nerve injury. According to the literature, massage therapy has been used to treat a number of diseases, such as infant brain maldevelopment, skin diseases, prenatal depression, chronic pain, cardiovascular diseases, immune diseases, cancer, neurodegenerative diseases, sleep, and other uncomfortable symptoms (Field, 2014). Pan et al. (2017) concluded that the effects of massage therapy are based on a mechanism involving the facilitation of blood and lymph fluid circulation, inhibition of erythrocyte aggregation, and decreases in viscosity and substance P levels in the blood, and an increase in β-endorphin levels. Their results demonstrated that massage therapy could increase the expression of nerve growth factor and decrease the secretion of tissue plasminogen activator and plasminogen activator inhibitor-1. These actions could accelerate rehabilitation after PNI (Xian et al., 2015). Wolny et al. (2017) applied massage to the descending part of the trapezius combined wrist mobilization directed at the median nerve. This procedure reduced the subjective symptoms of carpal tunnel syndrome and improved sensory function and sensory nerve conduction velocity. To date, extensive research has reported brain plasticity following PNI (Goswami et al., 2016; Bhat et al., 2017). Interestingly, several studies have focused on changes in brain plasticity following massage therapy. Ouchi et al. (2006) showed that massage therapy in the prone position could significantly increase local cerebral blood flow in the parietal cortex. Sliz et al. (2012) explored immediate neurophysiological effects of different types of massage in healthy adults. They found selective changes in the retrosplenial/posterior cingulate following reflexology massage. The current study has provided powerful evidence that adaptive cerebral plasticity after massage therapy remain even after a relative long period of time (4 weeks).

fMRI is considered an important neuroimaging technique for noninvasive observation of brain activity (Guerra-Carrillo et al., 2014). ALFF values are physiologically related to the spontaneous activity of a specific brain area and are measured using a method based on the fast Fourier transform of the resting-state time series for each voxel (Mohamed et al., 2004). Viswanathan and Freeman (2007) recorded changes in tissue oxygen levels in the visual cortex. They suggested that the BOLD fMRI signal primarily reflects synaptic activity, as well as neuronal activity. This index is highly time-stable in the resting-state and is often used as a biological marker for long-term intervention in various diseases (Küblböck et al., 2014). The excitatory/inhibitory balance between synapses is related to hemodynamics and indirectly influences the intensity of the BOLD signal; a negative BOLD signal indicates inhibition of synapse function (Lauritzen et al., 2012). Therefore, decreased ALFF values in the corresponding somatosensory cortex following PNI indicated reduced spontaneous (excitatory) neuronal activity. The changes that we observed in the contralateral somatosensory cortex following PNI were similar to what we found in our previous study (Wu er al., 2018). As the somatosensory cortex loses sensory input from the peripheral nerve, neuronal activity decreases. Evidence shows that input-deprived brain regions can become reactivated after reinnervation (Kaas and Collins, 2003; Wu et al., 2016). The increase in ALFF values following nerve repair demonstrate enhanced activity of related neurons and show the process of peripheral neural regeneration. Following massage intervention, the ALFF values in the somatosensory cortex increased; we can infer that this is related to the facilitatory effect of massage therapy on sensorimotor functional recovery. In our previous study of rats, the recovery of the affected hindlimb following sciatic nerve transection and repair significantly improved after the application of electroacupuncture. In those rats, we also noted an increase in ALFF value of the somatosensory cortex contralateral to the affected hindlimb (Wu et al., 2018). In the present study, after 4 weeks of intervention, the model group showed lower ALFF values than the normal group in the somatosensory cortex contralateral to the affected hindlimb, indicating suppressed spontaneous activity in that region after PNI. Additionally, compared with the model and sham-massage groups, the massage group exhibited significantly higher ALFF values in the contralateral somatosensory cortex. This indicates that massage therapy led to restoration of neuronal activity. The effect of massage on ALFF values in the present study was similar to that of electroacupuncture in our previous study.

The somatosensory cortex processes behavior-related somatosensory information (Kim et al., 2016). It integrates tactile, painful, and proprioceptive sensory information that is projected from the extremities through the thalamus. Thus, the clinical symptoms of PNI manifest as abnormal integration of sensory information. Chao et al. (2018) observed positive BOLD responses to forepaw stimulation in the medial thalamus, hypothalamus, and primary somatosensory cortex of the hindlimb area contralateral to the injured nerve following tibial and common peroneal nerves transection. The sustained activation in the contralateral primary somatosensory cortex, insula, and cingulate gyrus appeared immediately after spared nerve injury. In patients with complete median nerve injury at the wrist and delayed repair 2 years later, the response of the contralateral somatosensory cortex decreased during tactile stimulation of the fingers, while that in the ipsilateral primary somatosensory cortex increased (Fornander et al., 2016). Functions lost in the damaged cortex can be taken over by adjacent regions. Moore and Schady (2000) found that after injury, corresponding somatosensory cortex received sensory information from adjacent areas after PNI or amputation. Using fMRI, Qiu et al. (2014) showed that peripheral afferent dysfunction after brachial plexus injury caused the function of the corresponding cortex to be occupied by adjacent non-specific afferent cortical areas. Based on these studies, the function of the corresponding cortex may be partially replaced after PNI, and complete recovery of function is not guaranteed even after immediate repair (Jaquent et al., 2001). Massage therapy provides constant input of peripheral sensory information, which might prevent the corresponding cortex from being occupied by adjacent regions.

In accordance with another study (Philip and Frey, 2014), we found that ALFF in the somatosensory cortex ipsilateral to the affected hindlimb also increased. The increased ipsilateral somatosensory activation may be due to attenuated hemispheric inhibition associated with signal changes in the afferent somatosensory cortex. In this study, unilateral sciatic nerve transection induced suppressed local excitability in the contralateral somatosensory cortex. During the recovery process, massage improved restoration of local brain activity. Therefore, massage therapy may facilitate information integration by restoring the activity of somatosensory cortex to restore the sensory functions.

This study had several limitations. With humans, acquisition of functional images before clinical damage is not possible. Thus, at the beginning of the experiment, to be consistent with the clinical reality, we did not perform pre-surgery fMRI scans in our rats. However, we will explore dynamic changes in the brain before and after surgery in a follow-up study. Molecularly active substances can be used as indexes in future experiments, which will better explain the effect of massage. The difference between humans and rodents limited interpretation of the data. A correlation analysis between behavior assessments and ALFF values is necessary in a future study. We also need to explore the changes in brain plasticity in the acute period after PNI. Because most of the methods used in clinical treatment are implemented with different amounts of force, and the complexity and strength of the manipulation are related to the endurance of the patients and the personal level of the therapist, the application of machine-based massage therapy does not represent actual massage therapy very well.

Acknowledgements: We thank Department of Radiology, Fudan University Shanghai Cancer Center for their equipment support.

Author contributions: Conceptualization: XXX, XYH; methodology: XYH, MXZ, SJM; validation: ZZM; formal analysis: XXX, MXZ; writing-original draft: XXX, MXZ; writing review & editing: MXZ, JGX. All authors read and approved the final manuscript.

Conflicts of interest: The authors declare that they have no competing interests.

Financial support: This study was supported by National Key R&D Program of China, No. 2018YFC2001600 (to JGX); and Shanghai Science and Technology Committee of China, Nos. 18511108300 (to JGX), 18441903800 (to MXZ) and 18441903900 (to XYH). The funding body played no role in the study design, in the collection, analysis and interpretation of data, in the writing of the paper, or in the decision to submit the paper for publication.

Institutional review board statement: This study was approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine, China (approval No. 201701001) on January 12, 2017. The experimental procedure followed the United States National Institutes of Health Guide for the Care and Use of Laboratory Animal (NIH Publication No. 85-23, revised 1985).

Copyright license agreement: The Copyright License Agreement has been signed by all authors before publication.

Data sharing statement: Datasets analyzed during the current study are available from the corresponding author on reasonable request.

Plagiarism check: Checked twice by iThenticate.

Peer review: Externally peer reviewed.

Open peer reviewers: Michele R Colonna, Universita degli Studi di Messina, Italy; Gabriele Siciliano, Universita degli Studi di Pisa, Italy; Yu Lei, Huashan Hospital, Fudan University, China.

Additional file: Open peer review reports 13[Additional file 1].

Funding: This study was supported by National Key R&D Program of China, No. 2018YFC2001600 (to JGX); and Shanghai Science and Technology Committee of China, Nos. 18511108300 (to JGX), 18441903800 (to MXZ) and 18441903900 (to XYH).

 
  References Top

1.
Aboodarda SJ, Greene RM, Philpott DT, Jaswal RS, Millet GY, Behm DG (2018) The effect of rolling massage on the excitability of the corticospinal pathway. Appl Physiol Nutr Metab 43:317-323.  Back to cited text no. 1
    
2.
Aiello M, Salvatore E, Cachia A, Pappatà S, Cavaliere C, Prinster A, Nicolai E, Salvatore M, Baron JC, Quarantelli M (2015) Relationship between simultaneously acquired resting-state regional cerebral glucose metabolism and functional MRI: a PET/MR hybrid scanner study. Neuroimage 113:111-121.  Back to cited text no. 2
    
3.
Andrzejewski W, Kassolik K, Dziegiel P, Pula B, Ratajczak-Wielgomas K, Jablonska K, Kurpas D, Halski T, Podhorska-Okolow M (2014) Effects of synergistic massage and physical exercise on the expression of angiogenic markers in rat tendons. Biomed Res Int 2014:878095.  Back to cited text no. 3
    
4.
Bhat DI, Indira Devi B, Bharti K, Panda R (2017) Cortical plasticity after brachial plexus injury and repair: a resting-state functional MRI study. Neurosurg Focus 42:E14.  Back to cited text no. 4
    
5.
Casals-Díaz L, Vivó M, Navarro X (2009) Nociceptive responses and spinal plastic changes of afferent C-fibers in three neuropathic pain models induced by sciatic nerve injury in the rat. Exp Neurol 217:84-95.  Back to cited text no. 5
    
6.
Chao TH, Chen JH, Yen CT (2018) Plasticity changes in forebrain activity and functional connectivity during neuropathic pain development in rats with sciatic spared nerve injury. Mol Brain 11:55.  Back to cited text no. 6
    
7.
Chawla A, Spinner RJ, Torres Lizardi M, Yaszemski MJ, Windebank AJ, Wang H (2014) Non-invasive isometric force measurement of plantar flexors in rats. Muscle Nerve 50:812-821.  Back to cited text no. 7
    
8.
Dabbour RY, Hassan TA, Faqawi MS, Böttcher B (2018) Pain management during labour at the El-Emarati Hospital: a clinical audit. Lancet 391 Suppl 2:S35.  Back to cited text no. 8
    
9.
Diego MA, Field T (2009) Moderate pressure massage elicits a parasympathetic nervous system response. Int J Neurosci 119:630-638.  Back to cited text no. 9
    
10.
Field T (2014) Massage therapy research review. Complement Ther Clin Pract 20:224-229.  Back to cited text no. 10
    
11.
Field T, Diego M, Solien-Wolfe L (2014) Massage therapy plus topical analgesic is more effective than massage alone for hand arthritis pain. J Bodyw Mov Ther 18:322-325.  Back to cited text no. 11
    
12.
Fornander L, Nyman T, Hansson T, Brismar T, Engström M (2016) Inter-hemispheric plasticity in patients with median nerve injury. Neurosci Lett 628:59-66.  Back to cited text no. 12
    
13.
Goldman RI, Stern JM, Engel J, Jr., Cohen MS (2002) Simultaneous EEG and fMRI of the alpha rhythm. Neuroreport 13:2487-2492.  Back to cited text no. 13
    
14.
Goswami R, Anastakis DJ, Katz J, Davis KD (2016) A longitudinal study of pain, personality, and brain plasticity following peripheral nerve injury. Pain 157:729-739.  Back to cited text no. 14
    
15.
Guerra-Carrillo B, Mackey AP, Bunge SA (2014) Resting-state fMRI: a window into human brain plasticity. Neuroscientist 20:522-533.  Back to cited text no. 15
    
16.
Hillman EM (2014) Coupling mechanism and significance of the BOLD signal: a status report. Annu Rev Neurosci 37:161-181.  Back to cited text no. 16
    
17.
Hoptman MJ, Zuo XN, Butler PD, Javitt DC, D'Angelo D, Mauro CJ, Milham MP (2010) Amplitude of low-frequency oscillations in schizophrenia: a resting state fMRI study. Schizophr Res 117:13-20.  Back to cited text no. 17
    
18.
Jaquet JB, Luijsterburg AJ, Kalmijn S, Kuypers PD, Hofman A, Hovius SE (2001) Median, ulnar, and combined median-ulnar nerve injuries: functional outcome and return to productivity. J Trauma 51:687-692.  Back to cited text no. 18
    
19.
Kaas JH, Collins CE (2003) Anatomic and functional reorganization of somatosensory cortex in mature primates after peripheral nerve and spinal cord injury. Adv Neurol 93:87-95.  Back to cited text no. 19
    
20.
Kim SK, Hayashi H, Ishikawa T, Shibata K, Shigetomi E, Shinozaki Y, Inada H, Roh SE, Kim SJ, Lee G, Bae H, Moorhouse AJ, Mikoshiba K, Fukazawa Y, Koizumi S, Nabekura J (2016) Cortical astrocytes rewire somatosensory cortical circuits for peripheral neuropathic pain. J Clin Invest 126:1983-1997.  Back to cited text no. 20
    
21.
Kinkead B, Schettler PJ, Larson ER, Carroll D, Sharenko M, Nettles J, Edwards SA, Miller AH, Torres MA, Dunlop BW, Rakofsky JJ, Rapaport MH (2018) Massage therapy decreases cancer-related fatigue: Results from a randomized early phase trial. Cancer 124:546-554.  Back to cited text no. 21
    
22.
Küblböck M, Woletz M, Höflich A, Sladky R, Kranz GS, Hoffmann A, Lanzenberger R, Windischberger C (2014) Stability of low-frequency fluctuation amplitudes in prolonged resting-state fMRI. Neuroimage 103:249-257.  Back to cited text no. 22
    
23.
Labrecque M, Eason E, Marcoux S (2001) Perineal massage in pregnancy. Such massage significantly decreases perineal trauma at birth. BMJ 323:753-754.  Back to cited text no. 23
    
24.
Lauritzen M, Mathiesen C, Schaefer K, Thomsen KJ (2012) Neuronal inhibition and excitation, and the dichotomic control of brain hemodynamic and oxygen responses. Neuroimage 62:1040-1050.  Back to cited text no. 24
    
25.
Liao W, Li J, Ji GJ, Wu GR, Long Z, Xu Q, Duan X, Cui Q, Biswal BB, Chen H (2019) Endless fluctuations: temporal dynamics of the amplitude of low frequency fluctuations. IEEE Trans Med Imaging 38:2523-2532.  Back to cited text no. 25
    
26.
Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A (2001) Neurophysiological investigation of the basis of the fMRI signal. Nature 412:150-157.  Back to cited text no. 26
    
27.
Ma SJ, Yan JT, Tao R, Lu YJ, Wang CH, Pan JF, Ma Y, Zhou F, Bao JM, Fu LJ (2016) Effects of tuina combined with treadmill training on regeneration of sciatic nerve in rats. Zhongguo Kangfu Lilun yu Shijian 22:1276-1280.  Back to cited text no. 27
    
28.
Miller RH (2017) Neurobiology: A change of fate for nerve repair. Nature 551:41-42.  Back to cited text no. 28
    
29.
Mohamed MA, Yousem DM, Tekes A, Browner N, Calhoun VD (2004) Correlation between the amplitude of cortical activation and reaction time: a functional MRI study. AJR Am J Roentgenol 183:759-765.  Back to cited text no. 29
    
30.
Moore CE, Schady W (2000) Investigation of the functional correlates of reorganization within the human somatosensory cortex. Brain 123:1883-1895.  Back to cited text no. 30
    
31.
Neumann B, Linton C, Giordano-Santini R, Hilliard MA (2019) Axonal fusion: An alternative and efficient mechanism of nerve repair. Prog Neurobiol 173:88-101.  Back to cited text no. 31
    
32.
Ouchi Y, Kanno T, Okada H, Yoshikawa E, Shinke T, Nagasawa S, Minoda K, Doi H (2006) Changes in cerebral blood flow under the prone condition with and without massage. Neurosci Lett 407:131-135.  Back to cited text no. 32
    
33.
Pan F, Yu TY, Wong S, Xian ST, Lu MQ, Wu JC, Gao YF, Li XQ, Geng N, Yao BB (2017) Chinese tuina downregulates the elevated levels of tissue plasminogen activator in sciatic nerve injured Sprague-Dawley rats. Chin J Integr Med 23:617-624.  Back to cited text no. 33
    
34.
Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. London: Academic Press.  Back to cited text no. 34
    
35.
Philip BA, Frey SH (2014) Compensatory changes accompanying chronic forced use of the nondominant hand by unilateral amputees. J Neurosci 34:3622-3631.  Back to cited text no. 35
    
36.
Qiu TM, Chen L, Mao Y, Wu JS, Tang WJ, Hu SN, Zhou LF, Gu YD (2014) Sensorimotor cortical changes assessed with resting-state fMRI following total brachial plexus root avulsion. J Neurol Neurosurg Psychiatry 85:99-105.  Back to cited text no. 36
    
37.
Rogachov A, Cheng JC, Erpelding N, Hemington KS, Crawley AP, Davis KD (2016) Regional brain signal variability: a novel indicator of pain sensitivity and coping. Pain 157:2483-2492.  Back to cited text no. 37
    
38.
Sampaio-Baptista C, Sanders ZB, Johansen-Berg H (2018) Structural Plasticity in Adulthood with Motor Learning and Stroke Rehabilitation. Annu Rev Neurosci 41:25-40.  Back to cited text no. 38
    
39.
Schwarz AJ, Danckaert A, Reese T, Gozzi A, Paxinos G, Watson C, Merlo-Pich EV, Bifone A (2006) A stereotaxic MRI template set for the rat brain with tissue class distribution maps and co-registered anatomical atlas: application to pharmacological MRI. Neuroimage 32:538-550.  Back to cited text no. 39
    
40.
Sliz D, Smith A, Wiebking C, Northoff G, Hayley S (2012) Neural correlates of a single-session massage treatment. Brain Imaging Behav 6:77-87.  Back to cited text no. 40
    
41.
Sullivan R, Dailey T, Duncan K, Abel N, Borlongan CV (2016) Peripheral nerve injury: stem cell therapy and peripheral nerve transfer. Int J Mol Sci 17:2101.  Back to cited text no. 41
    
42.
Viswanathan A, Freeman RD (2007) Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity. Nat Neurosci 10:1308-1312.  Back to cited text no. 42
    
43.
Wan XF, Tang CL, Zhao DD, An HY, Ma X, Qiao TX (2019) Therapeutic effect of massage on denervated skeletal muscle atrophy in rats and its mechanism. Zhongguo Ying Yong Sheng Li Xue Za Zhi 35:223-227.  Back to cited text no. 43
    
44.
Wolny T, Saulicz E, Linek P, Shacklock M, Myśliwiec A (2017) Efficacy of manual therapy including neurodynamic techniques for the treatment of carpal tunnel syndrome: a randomized controlled trial. J Manipulative Physiol Ther 40:263-272.  Back to cited text no. 44
    
45.
Wu JJ, Lu YC, Hua XY, Ma SJ, Shan CL, Xu JG (2018) Cortical remodeling after electroacupuncture therapy in peripheral nerve repairing model. Brain Res 1690:61-73.  Back to cited text no. 45
    
46.
Wu R, Su L, Yang PF, Min Chen L (2016) Altered spatiotemporal dynamics of cortical activation to tactile stimuli in somatosensory area 3b and area 1 of monkeys after spinal cord injury. eNeuro 3:ENEURO.0095-0016.2016.  Back to cited text no. 46
    
47.
Xian ST, Yu TY, Pan F, Wu JC, Gao YF, Zhang LF (2015) Effects of massage on the expression of calcitonin gene-related peptide in dorsal root ganglion of chronic constriction injury rats. Zhongyi Xuebao 30:1311-1314.  Back to cited text no. 47
    
48.
Yang H, Long XY, Yang Y, Yan H, Zhu CZ, Zhou XP, Zang YF, Gong QY (2007) Amplitude of low frequency fluctuation within visual areas revealed by resting-state functional MRI. Neuroimage 36:144-152.  Back to cited text no. 48
    
49.
Zang YF, He Y, Zhu CZ, Cao QJ, Sui MQ, Liang M, Tian LX, Jiang TZ, Wang YF (2007) Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain Dev 29:83-91.  Back to cited text no. 49
    
50.
Zhang Y, Gao C, Chen D, Wang C, Chen L, Zhang Y, Li B (2019) Tuina Massage Improves Cognitive Functions of Hypoxic-Ischemic Neonatal Rats by Regulating Genome-Wide DNA Hydroxymethylation Levels. Evid Based Complement Alternat Med 2019:12820.  Back to cited text no. 50
    

P-Reviewers: Colonna MR, Siciliano G, Lei Y; C-Editor: Zhao M; S-Editors: Yu J, Li CH; L-Editors: Yu J, Song LP; T-Editor: Jia Y


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed442    
    Printed0    
    Emailed0    
    PDF Downloaded99    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]