Stimulated by Jung et al 2020.
This paper popped up on my searches because it had fibromyalgia in the abstract. I don’t deliberately search for fibromyalgia, but it is linked in the PubMed system of terms with myofascial pain, which I do search for each day, along with acup* OR electroacup* etc.
After pausing on the first author’s name, which sounded in my internal voice just like Zheng (Mandarin pronunciation), reminding me of the Admiral Zheng (1371-1433) I had been hearing about recently, I was intrigued by the idea of imaging neuroinflammation, and since it was in a journal to which I subscribe, I decided to look closer.
When I saw the full author list I realised that I know the last two authors – Richard Harris and Vitaly Napadow, and I wondered if I would find acupuncture somewhere in the paper. But alas no, a text search for ‘acup’ revealed nothing. I was still interested to find out what they had done, and since they are both well-known authors of acupuncture research I figured that was good enough to mention here.
MRS stands for Magnetic Resonance Spectroscopy. It has been around for several decades and was a natural extension of the phenomenon of nuclear magnetic resonance, first described by Isidor Rabi in 1938. Rabi went on to collect the Nobel prize for physics in 1944.
I will attempt a simple explanation without mentioning the mass of bottom quarks or the spin of a boso from NICE, who appears charming but is simply strange.
Some atomic nuclei have charge and spin characteristics that mean they act like little bar magnets with a plus pole and a minus pole… remember your iron filings from school? They stick to both ends but are not so interested in the middle bit. When you bring one bar magnet towards another, the free one swings around and attaches to the nearest end. So when you put these tiny bar magnets into a strong magnetic field (such as inside an MRI scanner) they all flip to align themselves in the lowest energy state they can achieve ie they don’t resist the field. When a smaller magnet is spun nearby, all the little bar magnets start to oscillate to and fro, and at a certain frequency range (perhaps 60–1000MHz) they resonate, like the wine glass singing when you rub your finger around it. Now this singing can be detected, and the pitch and volume will tell you how many like bar magnets you have in a particular place.
If the little bar magnet is a proton, and your subject is a bag of mildly salty water (the human body) then you can create an image based on the H20 distribution, and thus you have an MR image.
Well 1H (a hydrogen atom or proton) is probably the simplest and most ubiquitous little bar magnet we can look at, particularly in organic matter, but there are some others typically used in MRS in vivo: phosphorus, carbon, sodium and fluorine.
In vivo MRS is a non-invasive approach to studying metabolic changes in tissues by estimating the quantity of certain metabolites – molecules typically altered in certain disease processes in specific locations.
Briefly back to the physics! Molecules are a whole lot more complex than the single bar magnet of a proton, but if you tune in to the singing of protons and you suppress the noise from the ubiquitous water molecules, then the more subtle tunes made by other molecules appear. In MRS you can tune in to the signal from a molecule of interest and estimate the quantity in an area of interest. The MRS looks at a particular area based on an MR image called a voxel. A voxel varies in size but doesn’t get smaller than 1cm cubed – about the size of a sugar cube.
So finally, we come back to Jung et al. They used a voxel of 2x2x3cm, which is approximately the size of two standard Lego bricks stuck together, placed it covering the right insula and looked for choline and myo-inositol in the brains of patients with fibromyalgia (FM).
Choline and myo-inositol are markers for neuroinflammation. Choline is more abundant in the cell membranes of glial cells than those of neurons, so it has been linked to glial cell membrane turnover. Myo-inositol is linked to glial cell volume and neuroinflammation.
Jung et al found that choline was elevated in the anterior insula of patients with FM compared with healthy controls, but myo-inositol was not. Choline levels correlated with the symptomatology (pain interference) and that correlation was directly linked to changes in functional connectivity between the anterior insula and the putamen.
The putamen is involved in many aspects of movement, and the anterior insula in cognitive-emotional processing, interoception and consciousness. The insula contains many of our von Economo neurons – the very fast conducting pyramidal cells, of which human brains have the greatest number.
The paper contains other linked studies that suggest the increased choline may be related to astrogliosis and microglial activation as part of a neuroinflammatory process.
Well Vitaly has studied changes in objective markers including functional imaging changes in a chronic pain condition treated with electroacupuncture, which I have highlighted here before, and Richard has studied effects of acupuncture in FM, among other things. So, my guess is, given funding availability, we could see MRS being used in the future to study beneficial objective changes in the brains of chronic pain patients treated with acupuncture.
Such objective outcomes, as last week’s blog suggests, may mean that blinding is unnecessary, and the whole process can be simplified to some degree perhaps.
1 Jung C, Ichesco E, Ratai E-M, et al. Magnetic resonance imaging of neuroinflammation in chronic pain: a role for astrogliosis? Pain Published Online First: 25 January 2020. doi:10.1097/j.pain.0000000000001815
2 Lent J. The Patterning Instinct – A Cultural History of Humanity’s Search for Meaning. Prometheus Books 2017.
3 Maeda Y, Kim H, Kettner N, et al. Rewiring the primary somatosensory cortex in carpal tunnel syndrome with acupuncture. Brain 2017;140:914–27. doi:10.1093/brain/awx015
4 Harris RE, Zubieta J-K, Scott DJ, et al. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs). Neuroimage 2009;47:1077–85. doi:10.1016/j.neuroimage.2009.05.083
5 Harris RE, Ichesco E, Cummiford C, et al. Brain Connectivity Patterns Dissociate Action of Specific Acupressure Treatments in Fatigued Breast Cancer Survivors. Front Neurol 2017;8:298. doi:10.3389/fneur.2017.00298