This was written before I saw MsL's last post:
Two more comments, having read the portion of the article posted.
1. Classifying diseases in terms of their inflammatory profiles may make sense. Don't know. Please note however that this appears in the Journal of Medical Hypothesis, which means that you don't have to prove anything - by definition - it just has to appear plausible. And in that regard, note that the inflammatory profile of CRPS shifts dramatically over time, from a stew of proinflammatory cytokines, Substance P, TNF-[alpha], etc., to basically a single peptide, Calcitonin Gene-Related Peptide (CGRP).
This is significant because it's only been in the last year or so that researchers have focused on the "longitudinal profile" of CRPS. Thus if you go back only a year or two in the literature, you will see no attempt to segregate CRPS patients by stage of disease. See, Uceyler N, Eberle T, Rolke R, Birklein F, Sommer C, Differential expression patterns of cytokines in complex regional pain syndrome, Pain 2007; 132: 195–205
http://www.rsds.org/2/library/articl...erle_Rolke.pdf ; Alexander GM, van Rijn MA, van Hilten JJ, Perreault MJ, Schwartzmann RJ, Changes in Cerebrospinal Fluid Levels of Pro-inflammatory Cytokines in CRPS , Pain 2005; 116: 213-219
http://www.rsds.org/2/library/articl.../alexander.pdf
In support of the majority of his thesis regarding the role of inflammation in CRPS, Omogui relies primarily on Birklein F, Schmelz M, Schifter S, Weber M. The important role of neuropeptides in complex regional pain syndrome. Neurology. 2001 Dec 26; 57(12): 2179–2184. Yet the later article of Birklien and Schemlz appears to be the authors’ latest word on the subject. See, Birklein F, Schmelz M, Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS),
Neuroscience Letters 2008; 437: 199-202
http://www.rsds.org/2/library/articl...in_Schmelz.pdf at 201:
Inflammation in the classical sense with positive blood markers has not been proven, but any inflammation has a "neurogenic component." As indicated above, peripheral trauma, in particular if it is accompanied by partial peripheral nerve lesion, causes a rapid release of NGF and cytokines. Both are able to activate and sensitize primary afferents, locally at the injury site or proximally in the respective nerve trunk. Accordingly, increased levels of proinflammatory cytokines have been shown in CRPS skin by analysis of suction blisterfluids and in CRPS spinal fluid. Our own group concentrated on cytokines in blood samples. We have been able to demonstrate increased TNF-alpha in plasma samples of two different independent CRPS patients groups. Increase of TNFalpha in that study was correlated to mechanical hyperalgesia. In a very recent more extensive study we confirmed these findings-not only on protein but also RNA level in CRPS blood samples. Different proinflammatory cytokines were upregulated while antiinflammatory cytokines were downregulated in the patients.
Cytokines also increase the neuropeptide content of primary afferent neurons. Activation of sensitized primary afferents then causes an increased release of neuropeptides into the affected body region. Chronic release of neuropeptides might be responsible for the above-mentioned CRPS symptoms. In serum samples from patients with acute CRPS, CGRP, SP and bradykinin were found to be significantly increased, in particular when clinical inflammatory signs were present. Subsequent to these exploratory investigations, neurogenic inflammation was elicited directly in the skin by transcutaneous electrical stimulation via intradermal microdialysis capillaries by our group. We first investigated the flare by Laser-Doppler scanning on the affected and on the unaffected side in our CRPS patients. Neurogenic flare was significantly more intense in patients-on both the affected and the clinically unaffected side. Another characteristic of neurogenic inflammation in rodents is SP-mediated plasma protein extravasation (PPE). In healthy humans, C-fibers usually contain too little SP to induce PPE. In CRPS, however, significant PPE could be shown in almost all patients investigated. In contrast to the flare response, this increased PPE was limited to the affected side. These results suggested two possible pathomechanisms leading to facilitated neurogenic inflammation in CRPS-either increased release or hampered inactivation of neuropeptides, or both. In order to further unravel these mechanisms, we perfused SP in ascending concentrations through dermal microdialysis fibers in CRPS patients and controls. We found SP significantly more effective at inducing PPE in CRPS patients. Similar to the increased flare response,this increased responsiveness to SP was present on both the affected and unaffected limbs. [Footnotes omitted.]
However, when the first reported longitudinal study was done across the length of their disease, a different pattern emerged altogether. See, Schinkel C, Scherens A, Köller M, Roellecke G, Muhr G, Maier C, Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups, 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]
http://www.ncbi.nlm.nih.gov/pubmed/1...m&ordinalpos=2
Accordingly, the only longitudinal (pilot) study to date of CRPS across the disease cycle among a group of patients - as opposed to sampling CRPS patients as an undifferentiated group vs. controls - found that the "Determination of systemic inflammatory parameters is not yet helpful in diagnostic and follow-up of CRPS I," precisely the opposite result predicted by Omoigui, who maintains that diseases should be classified by their inflammatory profiles.
*
Which brings to mind the Riddle of the Sphinx: What walks on four legs in the morning, two at Noon and three in the evening? (Man)
2. I had seen the name of Sota Omoigui, MD before, but I couldn't recall seeing his departmental title: Division of Inflammation and Pain Research, L.A Pain Clinic, 4019 W. Rosecrans Ave, Hawthorne, CA 90250. At that point, I had no choice but to open his web page, but not to pop ups, etc.:
http://www.medicinehouse.com/ (Talk about something for everyone.)
That said, the man definitely contributed Chapter 23, "Cholesterol, interleukin-6 inflammation, and atherosclerosis—role of statins, bisphosphonates, and plant polyphenols in atherosclerosis and other diseases of aging," in Ronald Ross Watson (Editor), Douglas Larson (Editor)
Immune Dysfunction and Immunotherapy in Heart Disease, Wiley September 2007
http://www.wiley.com/WileyCDA/WileyT...fContents.html and he has 7 hits on Pub Med, so he remained a mystery to me.
That is until I came across the C.V. which he had submitted as a member of The FDA Advisory Committee on Anesthetics and Life Support Devices
http://www.fda.gov/downloads/Advisor.../UCM177291.pdf And to tell the truth, a sad read it is. Clearly a sharp guy, and yet . . . . Still, there those seven Pub Med references under his name, three of which, including the first part of the 3-part article Sandra pulled and an article on which his chapter in the Watson and Larson text is based, are available free of charge. (Just run a search in Pub Med under his name.)
I wish everyone a good day.
Mike
* In fairness to Dr. Omoigui, one could take the position that our knowledge of inflammatory processes was still woefully incomplete (as suggested by the conclusion of Schinkel et al). Yet to do so would be to reduce his "Law of Pain" to an article of faith.