Bring Your Own Resurrection Tape: Another CRPS Article

It's hard not to be insulted by some medical research.  That's when falling back on the kill-or-be-killed attitude necessary for those of us interpreting medical research with the disciplined skills inherent to advanced degrees in foreign language and literary criticism comes in so handy.

I believe in the placebo effect.  I believe that the power of the mind is unlimited.  I have experienced the placebo effect, and use it every day.  It's a bit of a perversion, to "use" the placebo effect, knowingly, daily, and to claim to rely on it, even.

Better to leave that claim out there, brazen and true, but unexplained and undefended.  I will just say that the creatures with whom I live all understand that an announcement such as "Talk to me in 20 to 40 minutes, when I will be feeling better, please!" can be taken seriously.

I could tell you the story of the time I was being coded due to a funky bad heart arrhythmia and deteriorating oxygen saturation, but the sound of my cardiologist's voice led me back to a sinus rhythm and an O2 sat at least over 85.  Over the backs of five loud, panicking medicos, Dr. Chang talked to me in a pleasant monotone.  His voice is not a drug, this wasn't an example of the placebo effect, more of mindful guidance, and a refusal to go down. I'm just saying -- my mind occasionally may be characterized as... open.

Remember Dr Andreas Goebel, from the Liverpool's Institute of Translational Medicine?  I believe his last splash in my CRPS pool came via a cannonball entry claiming that CRPS didn't have a causative relationship with trauma, and also sent another "cure" announcement off the high dive, involving IVIG (it's the go-to moderate difficulty entry in his competitive repertoire) and the designation of CRPS as an auto-immune disease.  The thing is, he wraps his stuff in elements of truth, and stays in the news.

This time, the article framing his study is called:  'Placebo therapy' ineffective...

The conclusion?  I mean, I could go on, but we might need to track down Dr. Chang, and I'm not sure he's even still living in the Western Region of the Lone Alp Territories, here in Tête de Hergé. I should've asked the man to make me a resurrection tape.  So let's just jump to the freaking conclusion of this humiliating study and forego cardiac and respiratory collapse, shall we?

Dr Andreas Goebel, from the University's Institute of Translational Medicine, explains: We found that patients experienced significant pain relief minutes after a placebo therapy, such as salt water injections, but unexpectedly at a later time, and even with repeated placebo applications, there was minimal or no impact on reducing the symptoms of the condition." 

The results suggest that CRPS will not improve naturally over time, and there is little fluctuation in the pain intensity of the condition. 

Dr Goebel added: "It seems that the brain of CRPS patients cannot be easily 'tricked' into believing that a dummy intervention is effective. This means that health specialists should be cautious when considering placebo interventions for these patients."

© 2013 L. Ryan

Procustean Science: Re-Gifting IVIG

Part of me doesn't even want to post this, as it is recycled material from the famous or infamous -- I cannot decide, discern -- Andreas Goebel, forever presenting IVIG as a silver bullet for CRPS.  That's okay, I have seen good things come from focused scientists.

But it seems to me, the layperson with a dangerous small bit of knowledge, that repackaging a theory every few years in the pretty wrapping paper of a new context eventually makes the re-gifting exercise less one of diverse generosity and more one of desperately searching for a respectable vehicle.

In his most recent reincarnation of IVIG as cure all, Dr.Goebel blithely tosses on the rubbish heap the notion of trauma/injury/physical insult as an inciting event in CRPS.  There has always been a caveat to that observation -- that many cannot recall an inciting event, that many cases of "spread" (Dear God, please give us a better and more accurate word!) occur without trauma, large or small, and so on.

Still, I'd wager that most of "us"experience onset, instances of "spread," and, according to most reports I've read of people in remission coming out of that remission, after some sort of inciting injury/insult/trauma.  Call me crazy... (I'll give you a few moments.) -- Call me crazy, but trimming a disease profile so it better fits in the box you're wrapping this year... doesn't make me all a-dither about what's under the Christmas tree.

It makes me want to gift you with "Procrustes" as a middle name.  Andreas Procrustes Goebel.

Dr. Goebel presents himself in the following way on various websites that deal with disease and (all) encompassing theories of immunology and auto-immune scenarios

I am a senior lecturer in pain medicine at the University of Liverpool, and an honorary consultant in pain medicine at the Walton Centre NHS Trust, both in Liverpool in the United Kingdom. After receiving my medical and doctoral degrees from the University of Würzburg in Germany, I trained in anaesthesia and pain medicine first in Germany, then at the Oxford School of Anaesthesia in the United Kingdom.  This was followed by further specialized pain training at University College London Hospitals, and interventional training in Notwill, Switzerland.  I completed a 2-year fellowship in post-trauma immunology at Harvard Medical School in Boston. My main professional interest is with the role of the immune system in chronic pain, and immune modulating drug treatments for unexplained chronic pain conditions. I have a particular interest in a condition called ‘Complex Regional Pain Syndrome’ (CRPS).

I am a fellow of the Royal College of Anesthaesthetists, a member of the British and German Pain Societies and the International Association for the Study of Pain, and founding member of the CRPS network UK.

All of my bitchiness about the window dressing aside, Dr. Goebel was kind enough to answer an email inquiring about any IVIG/immunotherapy ("immune modulating drug treatments for UNEXPLAINED chronic pain conditions"/CAPS mine, all mine) research being done in the U.S., as he is centered in the UK:

This is all experimental at the moment. The only US group which I am aware of, who is trying immune treatments relatively systematically, is the Philadelphia group. You might wish to inquire with Dr. Lopez: Enrique.AradillasLopez@DrexelMed.edu and inquire. 

I have not inquired, as my experience with the staff at Drexel University's Neurology Department has been abysmal, and that's adding a dose of "sweetness and light" to the assessment.*

Well, time to rein myself in and give you the latest Dr. Andreas Procrustes Goebel's  Bento Box for a treatment that may well have tremendous merit, despite how it may be overblown in its marketing hype. This is much easier to take than past incarnations, being constrained by the format of a clinical trial.

Low-dose intravenous immunoglobulin treatment for complex regional pain syndrome (LIPS): study protocol for a randomized controlled trial

Longstanding complex regional pain syndrome (CRPS) is refractory to treatment with established analgesic drugs in most cases, and for many patients, alternative pain treatment approaches, such as with neuromodulation devices or rehabilitation methods, also do not work. The development of novel, effective treatment technologies is, therefore, important.

There are preliminary data suggesting that low-dose immunoglobulin treatment may significantly reduce pain from longstanding CRPS. 

Methods: LIPS is a multicentre (United Kingdom), double-blind, randomised parallel group, placebo-controlled trial, designed to evaluate the efficacy, safety, and tolerability of intravenous immunoglobulin (IVIg) 0.5 g/kg plus standard treatment, versus matched placebo plus standard treatment in 108 patients with longstanding complex regional pain syndrome. Participants with moderate or severeCRPS of between 1 and 5 years duration will be randomly allocated to receive IVIg 0.5 g/kg (IntratectTM 50 g/l solution for infusion) or matching placebo administered day 1 and day 22 after randomisation, followed by two optional doses of open-label medication on day 43 after randomisation and on day 64 after randomisation.

The primary outcome is the patients'pain intensity in the IVIG group compared with the placebo group, between 6 and 42 days after randomisation. The primary trial objective is to confirm the efficacy and confidently determine the effect size of the IVIG treatment technology in this group of patients.Trial registration: ISRCTN42179756 (Registered 28 June 13).

Author: Andreas Goebel, Nicholas Shenker, Nick Padfield, Karim Shoukrey, Candida McCabe, Mick Serpell, Mark Sanders, Caroline Murphy, Amaka Ejibe, Holly Milligan, Joanna Kelly, Gareth Ambler



* LIFTED FROM A POST PUBLISHED OCT. 3, 2011:
Remember Dr. Schwartzman of Drexel University fame?  I was so excited at the thought of being Philly bound, and getting to see one of the world's best in the field of CRPS.  It did not work out, mostly because the rarefied air around experts makes them incapable of understanding the limitations of their own impossible schedules!  That's why they have experienced gate-keepers, usually older women with cigarette-ravaged voices and an attitude.  The gate-keepers get to tell all the patients to whom the expert has offered the moon that the moon is made of cheese. 

© 2013 L. Ryan

A Sensible Green Salad

It's both an irritant and a sputtering baby flame of hope that one wishes to privately tend, teasing with tendrils of dried moss, carefully offered wafts of fresh but humid air, then cautiously covered with a high tech cake dome, perfected "air" mixture piped in from the Perfected "Air" Mixture canister standing by.  We who tend are dressed, variously, in protective suiting:  high density yellow paper cloaks with plastic self-ties, elbow length dress gloves, Michael-Jacksonian masks (with some adjustments to the nose clip) mixed with slight variants of that wondrous Guy Fawkes, Anonymous hacktivists, V for Vendetta and Occupists masks, now wonderfully ubiquitous, even in my world where soma meets psyche for afternoon sex.  A little Marvin Gaye, some ripe figs.

What?  You're lost, you say?  Are you sure you should've revived this blog, profderien, O Retired Educator?

What fire are we nursing now with such ridiculous, ambiguous imagination -- and to mention hope so early on, have you finally lost your faculties?

There's a team of researchers, a joint sort of affair, kind of -- affiliated with the University of Liverpool’s Institute of Translational Medicine and the University of Pecs in Hungary -- that is bandying about the word "cure" and CRPS within the same sentence.  I know, I just recently posted about it... but then a few neural sparks made me search mine own blog, using as search term the very odd "Liverpool."

And I remembered Dr. Andreas Goebel.
And I remembered this craze of optimism, this careful tending of a flame, and the eventual realization that Goebel's pony has but one trick.
And that the trick is tantalizing, infuriating.  Tantalizingly infuriating?

The source of the piss on the baby fire?  Common sense, common experiences.  To say that CRPS is not a neurological disorder at all, and not (often) the result of trauma is to belie the experience of... well, almost everyone with CRPS, and almost every physician who has observed its onset and evolution.

The air up here in Hope Land is thin, and hallucination likely.

I'll spare myself the shame of reviewing every sarcastic post born of my anger at those pushing "cure" and "CRPS" within the same paragraph -- and here I'd temporarily lost my bearings over another Goebel article, another IVIG paean, another sweeping claim.

My return to sanity came from an effort to eat popcorn.  You take the hand, you approach it to the bowl of puffed grain, you grasp one (my preference) and you bring it to your mouth.  Except, as has been the case for a few days, my hand would not cooperate, despite the oxygen-deprived fish mouthing of my face, hungry for popcorn.  It either would decline to pick up a piece of the lightly salted kernel, or would manage that feat, only to drop it three inches below my gaping maw.

My return to sanity was bolstered by the pain  and trophic changes of a now dragging right foot, the gift of an ignorant neurologist who conducted an ignorant neurological exam, the very definition of trauma.

My return to sanity has most especially been paved by the searing path of pouring boiling water on my thighs three mornings in a row during that incredibly complicated process of making coffee.

And my return to earlier convictions cleared completely when I remembered that Dr. Goebel headed an earlier team which published a paper -- just in December 2012 -- that included a line that has haunted me, and driven me:

There are only few treatments, and there is no cure. The condition has continued to puzzle investigators. Bizarre aspects of its presentation have continued to emerge over the past 110 years, and although we now understand that CRPS is indeed associated with an initial local inflammatory response – without reported neutrophil invasion or overt tissue destruction [8] – the underlying cause has remained elusive. Over the course of the disease, initial limb signs generally mellow [9], however about 15% of patients continue to have unrelenting pain [5]; these patients' quality of life remains amongst the lowest reported in medical conditions [6].

Tonight, Fred and I cranked up the air conditioner and dined on a sensible green salad dressed with red balsamic vinegar, because we are out of white.

© 2013 L. Ryan

CRPS in the Context of (Neuro?) Autoimmunity (With Thanks to Mice)

The study suggests Complex Regional Pain Syndrome 

could be caused by harmful serum-autoantibodies

Researchers at the University of Liverpool have taken a major step forward in understanding the causes of a disorder which causes chronic pain in sufferers. 

Complex Regional Pain Syndrome (CRPS) is a serious condition affecting a limb after an – often small – accident or operation.  It can cause severe pain lasting many years, as well as limb swelling, hair and nail growth changes, and muscle atrophy, but until now there has been no clear evidence of the cause. 

Now the research team from the University’s Institute of Translational Medicine alongside colleagues at the University of Pécs, Hungary have successfully transferred antibodies from the serum of patients with CRPS to mice, causing many of the same symptoms to be replicated. 

Dr Andreas Goebel *, who works in the University of Liverpool and is a Consultant in Pain Medicine at The Walton Centre NHS Foundation Trust, led the study.  He said: “CRPS is a serious condition which isn’t fully understood.  The findings of this study hint at a cause for it – harmful serum-autoantibodies – and raise the possibility of finding a treatment.”

[Read more of the story HERE from HealthCanal - Health News]
[ * Dr. Goebel's considerable research in chronic pain and CRPS HERE]

What to say?  It sounds momentous, yes?  But really, quite a bit of research, years old already, has been done that points to "clear evidence of the cause." Unfortunately, "THE cause" sort of thinking goes hand-in-hand with the "Silver Bullet Cure" crowd, and denies the complexity of the "syndrome." Be that as it may, it's a reflection more on the dumbing-down of pseudo-medical journalism, and not a reflection on the quality or bounds of the research on which the article is "reporting."

Why, for instance, do proponents of immunological causation feel the need to ignore the brain?  Just thought I'd toss that out there, as something not particularly helpful, but indicative of either/or thinking that just does not fly when dealing with the intricate relations and processes of the human body.  The peripheral and central nervous systems and their functional counterparts as parasympathetic and sympathetic impulses/small fibre neuropathy/glands run amok (hypothalamic-pituitary-adrenal -- HPA -- axis dysfunction)/immune system dysfunction/inflammation/psychosocial and environmental influences/and the darned partridge in a pear tree.

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A CRPS-IgG-transfer-trauma model reproducing inflammatory 

and positive sensory signs associated with complex regional pain syndrome

ABSTRACT
The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8 days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS.

An interesting site:  Centre for Immune Studies in Chronic Pain

© 2013 L. Ryan