Dear, dear friend -

I am thrilled to read this thread and see not only what progress you are making, but the degree to which you have brought your doctors with you! It's really amazing all the way along. (The fact that I have been AWOL from the forum for much of the last six weeks is something I have to acknowledge but would just as soon pass over for now. Mea culpa.)

And as far as a couple of points you make, I think you're right on the money and it's helpful to me!

As to electrical stimulation and CRPS, the role of implant Motor Cortex Stimulation (MCS) has already received some attention in the literature, including in the treatment of dystonia, although as you know MCS is a FAR MORE INVASIVE PROCEDURE than tDCS. Here I just have a couple of abstracts. Motor cortex electrical stimulation applied to patients with complex regional pain syndrome, Velasco F, Carrillo-Ruiz JD, Castro G, Argüelles C, Velasco AL, Kassian A, Guevara U, Pain 2009 Dec 15;147(1-3):91-8 (link imbedded in title); and Pain relief and functional recovery in patients with complex regional pain syndrome after motor cortex stimulation, Fonoff ET, Hamani C, Ciampi de Andrade D, Yeng LT, Marcolin MA, Jacobsen Teixeira M, Stereotact Funct Neurosurg. 2011; 89(3):167-72. Epub 2011 Apr 13.

But what’s happened of significance is that we now have a model that explains why electrical stimulation, including my old unrequited flame, RUL ECT – Right Unilateral Electroconvulsive Therapy Treatment for CRPS, Michaels F Jr., Pract Pain Manage. 2008 March; 68-75 – actually benefit people with CRPS. And so long as tDCS is powerful enough to attack the underlying mechanism – and your recovery is compelling testimony in that regard – we can not only see how, but why it works. See, Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) type I, Walton KD, Dubois M, Llinás RR, Pain 2010 Jul; 150(1):41-51, which apparently demonstrates – to anyone with the training to read it – that CRPS is just another in a line of “thalamocortical dysfunctions” due to the generation of low-threshold calcium spike bursts by thalamic cells. (See, Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography, Llinás RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP, Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15222-7.) Now, finally, the authors have come out with an accessible (to mere mortals) free-text book chapter on the subject: Central Pain as a Thalamocortical Dysrhythmia: A Thalamic Efference Disconnection? Walton KD, Llinás RR, Chapter 13 in Translational Pain Research: From Mouse to Man, Kruger L, Light AR, editors, CRC Press (2010). And check out what they have to say about stimulation, albeit not with tDCS:

The use of deep brain stimulation (DBS) as a treatment in several disorders was recently reviewed (Kringelbach et al. 2007b). DBS has proven to be a successful treatment in some types of pain (Kumar et al. 1997; Nandi et al. 2003; Bittar et al. 2005a, 2005b; Rasche et al. 2006; Yamamoto et al. 2006; Kringelbach et al. 2007a) and other instances of TCD, particularly in Parkinson’s disease (Benabid et al. 2003). The effectiveness of this therapy is consistent with the mechanisms postulated above: High-frequency stimulation could raise the resting potential of RT or intralaminar neurons above the level of T-type Ca++ channel deinactivation, and thalamic cells switch from bursting to tonic firing. The effectiveness of motor cortex stimulation in treating some cases of neuropathic pain (Carroll et al. 2000; Katayama et al. 2001a, 2001b) may be understood as resulting from top-down thalamic depolarization. It should be noted that the qualified success of this approach speaks to the challenge of modifying the thalamocortical loop using a depolarizer effectively situated outside the system. Recent advances using transcranial magnetic stimulation may similarly derive their effectiveness from a temporary rise in thalamocortical resting potential.

Now, as to your relapse with a cold, that too is consistent with what is known about one particular lingering inflammatory aspect of CRPS. Specifically, although most of the neuro-inflammatory action of CRPS occurs in the acute stage, there’s one character that hangs around for the duration: calcitonin gene-related peptide (CGRP). To begin with, check out the follow abstract, which I have color-coded in the hope that a few brave souls may follow along: See, Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups, Schinkel C, Scherens A, Köller M, Roellecke G, Muhr G, Maier C, Eur J Med Res. 2009 Mar 17; 14(3): 130-5.

Abstract
OBJECTIVES: The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet.

METHODS: To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C).

RESULTS: No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable.

CONCLUSION: Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory parameters is not yet helpful in diagnostic and follow-up of CRPS I. [Emphasis added for some statistically significant findings, although the authors were apparently hoping for more.]

PMID: 19380284 [PubMed - indexed for MEDLINE]

Now here’s what CGRP does:

Neurogenic inflammation is also mediated by the release of the CGRP from sensory neurons [9,25]. CGRP does not affect vascular permeability but does induce neurogenic vasodilatation via a direct (i.e., endothelium-independent) relaxation of vascular smooth muscle. CGRP containing sensory nerves directly innervate the smaller arteries, coming into close apposition of smooth muscle cells expressing the CGRP (CRLR) receptor.

Notes
9. Brain, SD. Sensory neuropeptides in the skin. In: Geppeti, P.; Holzer, P., editors. Neurogenic Inflammation. Boca Raton: CRC Press; 1996. p. 229-244.
25. Peroutka SJ. Neurogenic inflammation and migraine: implications for the therapeutics. Molecular interventions. 2005 Oct;5(5):304–11. [PubMed]

Post-junctional facilitation of Substance P signaling in a tibia fracture rat model of complex regional pain syndrome type I, Wei T, Li WW, Guo TZ, Zhao R, Wang L, Clark DJ, Oaklander AL, Schmelz M, Kingery WS, Pain. 2009 Aug;144(3):278-86.

And here is a recent abstract on the general immunological aspects of CGRP, e.g., what may have brought it to the fore when you had your cold, Modulation of immune responses by the neuropeptide CGRP, Holzmann B, Amino Acids. 2011 Nov 24. [Epub ahead of print]

Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Germany, holzmann@chir.med.tu-muenchen.de.

Abstract
The peripheral nervous system is connected with lymphoid organs through sensory nerves that mediate pain reflexes and may influence immune responses through the release of neuropeptides such as calcitonin gene-related peptide (CGRP). Local and systemic levels of CGRP increase rapidly during inflammatory responses. CGRP inhibits effector functions of various immune cells and dampens inflammation by distinct pathways involving the amplification of IL-10 production and/or the induction of the transcriptional repressor inducible cAMP early repressor (ICER). Thus, available evidence suggests that, in neuro-immunological interactions, CGRP mediates a potent peptidergic anti-inflammatory pathway.

PMID: 22113645 [PubMed - as supplied by publisher]

Now what, you might ask, do thalamocortical dysrhythmias and CGRP have to do with one another? There, I’m afraid I can only direct you to the tale of The Blind Men and an Elephant. In other words, and in so far as I know, those departments aren’t speaking with each other, yet. (A PubMed search of “thalamocortical CGRP” drew a blank.) To be continued . . . .

Mike


PS And thank you, I have ordered and look forward to reading Pain: Brain Stimulation in the Treatment of Pain (Disability Studies)
Helena Knotkova et al, editors, Nova Science Pub Inc. (2010).