30,000 fibromites subscribe to PatientsLikeMe (PLM), submitting medical history, medications prescribed and a subjective pain & fatigue score. Site FAQ is unashamed in disclosing that information is for sale, the loss of privacy being traded against useful efficacy reports on interventions.  Epidemiological comparisons between climatically alike countries Canada/Baltic states and Australia/NZ wasn’t of as much interest as was extracting timeframe from first symptoms to the patient’s obtaining a diagnosis of FM. Although India’s supremacy isn’t statistically significant (Mann-Whitney non-parametric test is around the median, rather than averages) at reducing doctor-shopping in order to find an enlightened one, this issue is nonetheless worth visiting. Which is where the past few months went!india

First observation was that doctors aren’t quite so other worldly as in the West, and as a service provider they’re relatively cheap. Few bucks for a consultation, which can easily be circumvented since pharmacies don’t require a script. The GP competes with doctors of Ayurvedic medicine using traditional methods, regulated and funded by Govt. The most famous advocate, Deepak Chopra is currently undertaking clinical trials into efficacy across 6 Universities (including Harvard). Practitioners questioned on therapy’s mechanisms seemed well informed. Fabricated pharmaceutical trial reports in Hyderabad is a recent cloud of infamy over the 1000 generic drugs suspended by the European Drug Agency, but scientific research has been less creatively and more rigorously innovative. An excellent appraisal of other’s studies on active therapies for fibromyalgia out of Delhi ‘Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review’ was sufficiently impressive to warrant linking of an excerpt under Downloads.

A second observation is that meditation and yogic thought were embraced by a disproportionate number of foreigners. Rishikesh is the usual destination, but an interest in Iyengar yoga led down the coast through Pune (BKS’s hometown) to Goa (more than just a beach!). The Himalayan Iyengar school relocates here for the winter, running Yoga retreats like bootcamps. Although the practice includes props used to support chronic ailment sufferers in position, the 4 hours were intense. Describing their teaching that “… all myalgias can be fixed by hanging upside down” as lacking evidence base is an understatement, but the idea of tackling dysautonomia by increasing pressure upon baroreceptors could indeed have merit. At a nondescript studio in Koregaon Park, Pune the class concluded with assessment of disposition and dietary recommendations. This picked up lifestyle behaviors that preceded contraction of FM, and was quite in accordance with science (© Elsevier). Yoga is described as India’s gift to the world, and local surgeon Dr Ranjit Rao shares his insights “Chronic pain conditions such as …, and fibromyalgia are often better managed with a holistic approach that includes yoga as well as other modalities.” His book ‘Meditation & Martini‘ attempts to bridge the gulf between advocates of pharmacotherapy and self-healing.
Gooders*, but is it effective? A query on PLM which ranks all interventions by patient’s score puts yoga third, behind LowDose Naltrexone and D-Ribose (mitochondrial fuel supply). Surprisingly, theCochraneLibrary.org has very little to contribute. Of 34 conditions treated by yoga reviewed systematically, ranging from epilepsy to dementia there’s no report on benefit in musulo-skeletal conditions (bar Prof Wieland’s in-progress evaluation of the literature for chronic lower-back pain). Rheumatology has focused overmuch upon lifelong dependence on palliative drugs at the expense of multi-disciplinary therapy, but another excerpt scanned this time from ‘Yoga for Arthritis‘ out of Swami Vivekananda Yoga press in Bangalore is rather more inclusively enlightened.

* Naval slang, translated: ‘Good as’ can be expected, in an otherwise hopeless situation. Actually, I’ve always had a healthy respect for India.

An alternative med.

Before OMG there was om. Negativity of previous posts must be redressed by suggesting a couple of ways to take charge over the body’s natural reactions to an often harsh world. Traditional eastern wisdom has recently been embraced by psychologists and business coaches alike. One can follow a mindfulness franchise on the strength of empirical evidence such as that published by Prof Richie Davidson. ‘Alterations in Brain and Immune Function Produced by Mindfulness Meditation’ , 2003 or ‘A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation’, 2013. Bill Malarkey published ‘Workplace based mindfulness practice and inflammation: A randomized trial’ in 2013 but his unfortunate name may prevent it’s being taken seriously. Both studies used Kabat-Zinn’s MBSR as an intervention, although following Vidyamala Burch is made easier by the offered product sample at Breathworks.  Ahhh!, the  rheumatologist detractors cry, these investigations are predicated on antibody measures and inflammatory markers such as C-Reactive Protein – which we deny being manifest in fibro!theUniverse
For you skeptics there’s the second, harder path. Let’s start from the premise that FM is a manifestation of a dysregulated cortisol/adrenalin factory – the HPA axis. Deep in our monkey brain is the amygdala which fuels the fight or flight adrenergic pathway, however this is a coarse control since chemical metabolism takes time. Calming electrical override is by the parasympathetic nervous system vagus nerve with help from serotonin-fired neural dopamine fueling a (hopefully) rational prefrontal cortex. Unfortunately, fibro and CFS sufferers lack this moderating instantaneous control as evidenced by reduced heartrate variability. Ashok Gupta’s solution is to re-programme the amygdala. Good luck with that, however evolving tens of thousand years isn’t a promising intervention. <Update Feb 2015: Apologies, Ashok-ji. I’d overlooked December’s report in Arthritis & Rheumatology ‘Overlapping Structural and Functional Brain Changes in Patients With Long-Term Exposure to Fibromyalgia Pain’. The amygdala changes in the right-hand diagram are associated with chronic pain causation…image002

…returning to neuroimmunopharmacology> Parasympathetic neurotransmitter Acetylcholine can inhibit inflammatory InterLeukin-6 (that alone is worth thinking about for its role in TMJD resulting from teeth grinding). Not that you’re going to meditate out of a fever, rather the need is to put the brakes on auto-immune pathways. IL-6 and IL-1 deplete Tryptophan, which we’d all prefer be used in creation of serotonin and ATP for energy but through Tumour Necrosis Factor it’s dumped. It’d be great to block TNF-α upfront through aggressive biological agents such as etanercept or adalimumab, but as rheumatologists deny FM’s suitability this won’t eventuate. Blocking IL cytokines is an even better idea, since Profs Hutchinson and Watkins showed neuropathic pain can be suppressed with naloxone – a shorter acting version of the opioid dependency treatment naltrexone. The diagram in Younger & Stringer et al article: Daily cytokine fluctuations, driven by leptin (tells the hypothalamus to get prolactin out there, but let’s not go there), puts these interactions much more clearly 😉image002
Analysis, paralysis. The neuroimmunologists and endocrinologists weaving logical arguments is messy theory, but the practice is up to your own mind. There’s so little profit to be made that pharma won’t be sponsoring studies into a quickfix pill – waiting for lowdose naltrexone proponents to capitalize on successes by Prof Younger, with approval to market seems most unwise. A mindful approach is more achievable than your cerebral cortex would think!

Fibromyalgia breakthrough!!!

A reason for the perplexing nature of FM syndrome has been found. It’s an ophthalmic disorder afflicting the ability of the sufferer’s specialist to discern the blindingly bloody obvious. This monochrome blindness results in denial of discernable difference between pathology results for patients and healthy controls. It’s 20 years since Wolfgang Muller determined such a difference in serotonin levels between fibromyalgics (‘GTM’ on the right) and healthy controls, with less than 1 in 10,000 possibility that it arose due to chance.Muller1993

Jascko, Hepp and Sprott et al decided that “Serum serotonin levels are not useful in diagnosing fibromyalgia”, although their immunoassay showed a range of 10-115ng/ml in patients – compared to 131-322ng/ml measured in the control group. Why there’s as many fibromites prescribed serotonin boosters as are treated with anti-convulsants*, without pathology evidence confounds me. Eduardo Ortega has led many discoveries of markers such as the inflammatory Interleukin-8. Hollenberg and Blanco et al found ten times the number of mast cells in FM skin, releasing inflammatory histamines when triggered. Cordero, deMiguel and Sánchez Alcázar et al studies also show no overlap in the FM or healthy ranges of the cell fuel ‘ATP’, oxidative stressor MDA, or its peroxidation counterpart catalase between their samples of three dozen women. Although a bonus that they publish in the open-access Public Library of Science, it’s disappointing that peer-reviewed journals showing interest are the likes of the obscure ‘Mitochondrion’. Contrast this with the publicity afforded sponsorship by Eli-Lilly of Dr Frank Rice’s findings of peripheral blood vessel pathology – announced in the American Academy of Pain Medicine and lauded widely in mainstream press articles for months as a breakthrough, along with commentary which “….explains why some selective serotonin reuptake inhibitors such as Cymbalta seem to help.

Although no one test has specificity to exclude Rheumatoid Arthritis or depression, in totality there is overwhelming evidence for an exact diagnostic determination by the lab. Assuming impartiality, of course. When Dr Bruce Gillis declared “..no competing interests” in ‘Unique Immunological Patterns in Fibromyalgia’, he clearly wasn’t speaking as CEO of his company which markets the fmtest ®. Medical evidence basis demands a decision which disproves any element of chance or individual perspective. The humanities are somewhat more subjective, and in being so are also sensitive to the person. Hamlet avoids an argument by not passing judgement on a seemingly black and white issue by proclaiming “There is nothing either good or bad, but thinking makes it so… “.

*Endep & Cymbalta vs Lyrica & Neurontin