The Effect of Spinal Manipulation on Brain Neurometabolites in Chronic Nonspecific Low Back Pain Patients: A Randomized Clinical Trial
SOURCE: Irish Journal of Medical Science 2019 (Nov 26) [Epub]
Daryoush Didehdar, Fahimeh Kamali, Amin Kordi Yoosefinejad, Mehrzad Lotfi
Department of Physical Therapy,
School of Rehabilitation Sciences,
Shiraz University of Medical Sciences,
BACKGROUND: In patients with chronic nonspecific low back pain (NCLBP), brain function changes due to the neuroplastic changes in different regions.
AIM: The current study aimed to evaluate the brain metabolite changes after spinal manipulation, using proton magnetic resonance spectroscopy (1H-MRS).
METHODS: In the current study, 25 patients with NCLBP aged 20-50 years were enrolled. Patients were randomly assigned to lumbopelvic manipulation or sham. Patients were evaluated before and 5 weeks after treatment by the Numerical Rating Scale (NRS), the Oswestry Disability Index (ODI), and 1H-MRS.
RESULTS: After treatment, severity of pain and functional disability were significantly reduced in the treatment group vs. sham group (p < 0.05). After treatment, N-acetyl aspartate (NAA) in thalamus, insula, dorsolateral prefrontal cortex (DLPFC) regions, as well as choline (Cho) in the thalamus, insula, and somatosensory cortex (SSC) regions, had increased significantly in the treatment group compared with the sham group (p < 0.05). A significant increase was further observed in NAA in thalamus, anterior cingulate cortex (ACC), and SCC regions along with Cho metabolite in thalamus and SCC regions after treatment in the treatment group compared with the baseline measures (p < 0.05). Also, a significant increase was observed in Glx (glutamate and glutamine) levels of thalamus (p = 0.03). There was no significant difference in terms of brain metabolites at baseline and after treatment in the sham group.
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CONCLUSION: In the patient with low back pain, spinal manipulation affects the central nervous system and changes the brain metabolites. Consequently, pain and functional disability are reduced.
KEYWORDS: 1H-MRS; Low back pain; Spinal manipulation
From the Full-Text Article:
Nonspecific chronic low back pain (NCLBP) is common disease in the lumbar area without any neurologic signs and specific reasons.  NCLBP accounts for 90% of the chronic low back pain (CLBP) cases. [2, 3] This disorder, which is associated with pain and disability, negatively affects the patient’s quality of life, productivity, and occupation. [2, 4] In chronic pains, after recovering from the early damage, pain is still perceived, demonstrating the role of changes in the function of the central nervous system(CNS).  According to the Tracey theory, pain is transformed from acute to chronic due to hypersensitivity of pain-processing network in CNS.  Hardy (1950) stated that chronic pain and hyperalgesia occurred following the initial damage due to increased CNS activity and its sensitization. 
Therefore, chronic pain and prolonged sensory impairment following an injury is owing to the increased CNS excitability involving pain or sensitization. [5, 7] In addition, studies have shown that CLBP causes central sensitization [8, 9], and patients with CLBP are hypersensitive to painful stimuli due to neuroplastic changes.  However, in patients with NCLBP, following a physical activity, the blood flow increases in regions associated with pain matrix (SSC, insula, and frontal cortex) Moreover, in NCLBP patients compared with healthy individuals, neurochemical metabolites decrease in the DLPFC, thalamus, and orbitofrontal cortex. [2, 11–15]
To treat and resolve issues associated with NCLBP, medical treatments and physiotherapy are recommended. Their purpose is to reduce pain and disability caused by NCLBP. [10, 16, 17] Spinal manipulation is a successful, cost-effective, and non-invasive treatment for NCLBP. [16, 18] Researches have confirmed the effect of manipulation on function improvement and pain reduction in patients with NCLBP. [19, 20] The neurophysiological mechanism of manipulation refers to the ability of the central nervous system to modulate sensory information. 
To evaluate the effect of spinal manipulation on patients’ brain with NCLBP, modern imaging techniques, such as functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), and 1H-MRS, are used.  1H-MRS is a non-invasive technique that measures the level of metabolites such as glutamate, glutamine, N-acetyl aspartate (NAA), creatine (Cr), myo-inositol, and choline (Cho) in the living human brain.  The NAA metabolite is synthesized in neurons and reflects the density of the neurons, and its reduction indicates the loss of the neuronal function.  Cho metabolite represents the health of neuron membranes, and its changes reflect upon the nervous system impairment.  Glutamate and glutamine (Glx) is the main excitatory neurotransmitter of the brain, binding to both ionotropic and metabotropic receptors that play an important role in pain. 
Studies have indicated eurometabolite changes in different regions of the brain (related to pain matrix area) in patients with chronic low back pain. [13, 15, 22, 25, 26] Certain studies suggest that neurobiological changes play important roles in the manifestation of chronic pain and its treatment. [13, 15, 22, 25–27]
There is limited knowledge about the neurobiological changes in pain-processing regions associated with chronic pain following manipulation therapy; accordingly, the aim of this study was to determine the effect of spinal manipulation therapy on the neurometabolites of the brain and neurochemical changes in neuronal surfaces using the 1H-MRS technique as a precise, reliable , and preferred method in patients with NCLBP. We hypothesized that the brain metabolite change after treatment by the spinal manipulation.