Kitty -
Thanks. So far I've gotten through 26 of the 64 abstracts, which is to say that I'm back to 2001. They generally fall into three categories: (1) the use of low dose naltrexone (NXT) to potentiate reduced or even very small doses narcotics, e.g. as a "combo drug," (2) as a stand alone drug for diseases such as primary progressive MS or Fibromyalgia when individuals had high sedimentation rates, suggesting that NXT was most effective in the presence of a general inflamatory process, or (3) as an aid in the testing of the true subject of the study, e.g. to determine whether analgesic Substance X worked through opioid receptors.
In light of the fact that AiKane's doctor wasn't giving him an opioid, that would appear to rule out it's use as a potentiator.
More to the point, there has been a substantial amount of research to date suggesting that CRPS has its most active inflammatory components only during the "acute" stage of the illness, typically a matter of 4 - 6 months. See, e.g., Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS), Birklein F, Schmelz M,
Neurosci Lett. 2008 Jun 6;437(3):199-202, at 201, free full text at
http://www.rsds.org/2/library/articl...in_Schmelz.pdf (noting more overt indications of infalamtory processes during acute stage of disease); 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.]
PMID: 19380284 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum
My naive hunch - of the last couple of hours - is that this is the reason why NXT isn't getting as much play in the CRPS medical community as it may be getting elsewhere. Put it another way, three years ago I was trying to run with a study that had come out showing elevated level of IL-6 in the spinal fluid of CRPS patients - others were later unable to replicate the results - but in the meantime, on what was then my annual pilgrimage to Rochester MN to see family and friends and go through the Mayo Clinic, I actively sought an appointment in the Division of Neuroimmunoloy of the Dept. of Neurology, but they catagorically refused to see me. Turns out they didn't regard CRPS as a neuroimmune condition.
Whether the presence of CGRP (p = 0.007!!!) changes that, and in particular provides any possible role for NXT requires going beyond the abstracts and reading the available articles on the use of the drug in MS and Fibro to see what is the hypothisized mechanism of action. And if it's through TNF-alpha, then it's probably safe to assume that it would have as little effect on chronic CRPS as does Remicade. Although potentiating reduced dose narcotics would be a wonderful thing in and of itself, especially with regard to GI motility.
Of course, I didn't know anything about the apparent anti-inflammatory aspect of NXT when I went off half-cocked on Friday. I even assumed that NXT would cancel out the naturally occuring opioids in the body. To the contrary, it may potentiate those as well,
which may have been where AiKane's doctor was going in the first instance. But from what little I have read about the use of NXT in MS, the action appears to be in it's anti-inflammatory capacity, as opposed to a palliative effect. That said, if it turns out I got remotely in the ballpark regarding the usefulness of NXT in CRPS (or lack thereof) then I just got lucky, relying on labelling the FDA has yet to update.
Mike