The long and the short of it is that one or more "cures" for acute CRPS/RSD are already well established for people in the early or "acute" stages of the illness: roughly speaking within four to six months of the onset of symptoms. But overcoming the substantial inertia that may stymie their implementation is another matter.

While neither (or any of the three, depending on how you look at it) of these treatments not currently available, in one case, that is true only as to the U.S. civilian population. Two, small and well written articles set the stage nicely:

A unique presentation of complex regional pain syndrome type I treated with a continuous sciatic peripheral nerve block and parenteral ketamine infusion: a case report, Everett A, Mclean B, Plunkett A, Buckenmaier C, Pain Med. 2009 Sep;10(6):1136-9. Epub 2009 Sep 9; and

Successful Intravenous Regional Block with Low-Dose Tumor Necrosis Factor-[Alpha] Antibody Infliximab for Treatment of Complex Regional Pain Syndrome 1, Bernateck M, Rolke R, Birklein F, Treede RD, Fink M, Karst M, Int Anesth Res Soc. 2007;105(4):1148-1151.

The articles are important for two very different reasons. As to the first, Col. Chester 'Trip' Buckenmaier, III, USAF, is one of our great unsung champions. As a newly-minted anesthesiologist at Walter Reed, c. 2001, then-Captain Buckenmaier persuaded his superiors to allow him to take what was then a new and exciting clinical fellowship at Duke, in continuous regional anesthesia (CRA). And when the Iraq War started, he was on one of the first planes out, with his bags filled with as many pumps and bags of lidocaine as he could carry. See, e.g., Doctor Recalls First Battlefield Use of Regional Anesthesia in Iraq, Rudi Williams, American Forces Press Service, May 25, 2004. Very long story short, it is because of his work that it is TBI and not CRPS that has become the defining war-related injury of the last decade.

So flash forward to 2008, a 17 year-old incoming West Point cadet twists her ankle during basic training, and a week later she's diagnosed with suspected CRPS. And let me stop right here and say that the one thing that's unique about military medicine in the U.S. - especially as to service academy cadets - is that it values the DOD's investment in human capital. (And what a shockingly foreign concept that is to those who do not have the benefit of a "single payer system.") In any event, she's tossed into a helicopter, and flown to Walter Reed, where she's rushed to ICU and hooked up simultaneously with CRA and a ketamine infusion for good measure. 5 days later she's discharged, recovered, and six months later was training for marathons. Her doctors then publish the case report lamenting about the difference in the standard of care with the civilian sector. But they may yet have the last laugh, where they are in the middle of a Dept. of Veterans Affairs funded study comparing the outcomes among some 500 wounded service personnel, grouped by matching pairs as to age, nature of injury, etc., controlling for everything except whether the patient received CRA, and on that each of the pairs are split down the middle, looking for the onset of complications, primarily CRPS.

The study is so large it's being run out of three of the largest military hospitals in the country, and when it concludes, it will have the statistical power to allow its authors to exert some leverage over the entrenched interests in the civilian medical sector. And hopefully I will not be seen as speaking out of turn if I say that it is, after all, a culture which appears to value CRA really as a prophylactic for surgeons, as opposed to -say - Duke's Pain Management Center, in the same Dept. of Anesthesiology - which does not offer CRA to anyone whomsoever who walks/limps in off the street Dare I even suggest that it might have something to do with not wishing to dry up their business? . . . All I know is that repeated calls on my part to Duke's Pain Management Center - seeking clarification as to why CRA was not among the available treatments listed on its website - were not returned. That, and that and I understand that CRA is currently the treatment of choice in France and Germany - the latter in particular - for suspected cases of CRPS, within days on the onset of symptoms.

The second article is of interest because it ties in so well to what is now known of the acute stage, a world of neuro-autoimmune disorder. See, e.g.,
Autoimmunity in Complex-Regional Pain Syndrome, Blaes F, Tschernatsch M, Braeu MD et al., Ann. N.Y. Acad. Sci.2007;1107: 168–173; and, Autoantibodies in complex regional pain syndrome bind to a differentiation-dependent neuronal surface autoantigen, Kohr D, Tschernatsch M, Schmitz et al, PAIN 2009; 143:246–251.

And at least as far as "Successful Intravenous Regional Block with Low-Dose Tumor Necrosis Factor-[Alpha] Antibody, etc." is concerned, I don't see anything more nefarious at play than the sad state of funding for biomedical research in the United States: even though at least 10% of the adult population suffers from some form of a chronic pain condition, in - I believe - 2010 the total amount spent on pain studies of any kind represented only 0.6% of the grants awarded by the NIH. And there's a strait forward explanation: due to the ever shrinking budget for all things science in the federal budget (and next year looks like the worst since the Soviet's launched Sputnik) the NIH tends to favor studies with matching industry money. And therein lies the rub: private dollars will be spent only on those drugs and devices that still have a healthy patent life. In one "swell foop" that takes care of infusions of any kind with generic anesthetics: whether ketamine infusions or continuous regional anesthesia.

To put this in focus, I've put the following and admittedly absurd scenario to a number of doctors in academic medical practice: Imagine that there are 100 published case reports and small studies showing complete cures in patients with severe psoriasis who took a Nembutal and then removed all their clothes and walked around naked for two hours every night on either side of Midnight [Standard Time] for the five nights straddling the full moon, during each of the three months straddling the summer solstice, would the NIH fund a study of 400 - 500 matched pairs of subjects, where one of the two took the barbiturate and the other a placebo. And in my under-powered and non-randomized survey, I got only one answer. No.

And studies with even brand new TNF[a]-antibodies are unlikely to receive as much as a donation of enough medication to run a study. Why? Because the idea of independent researchers running a study with any statistical value on a drug that's already been approved for release is fundamentally abhorrent; if significant side-effects in populations of "real patients," including those with "co-morbid" conditions that might have been excluded or at the least "minimized" in earlier industry-sponsored studies, then that information would have to work its way into the FDA-approved "prescribing information." Indeed, "after-market" information of this sort has resulted in the recall of medications for as long as the FDA has had jurisdiction over the use and distribution of prescription drugs. Why risk a good thing when the potential upside to the manufacturer would be a trivial amount of sales in a minor sub-market? Or so my physicians have explained the problem to me, in one case when all that was sought was a small supply of an otherwise relatively expensive drug.

Further complicating the issue is the role of for-profit insurance companies, who have become accustomed to very large, double-blind multi-center Phase III testing, before large pharmaceutical firms (Big Parma) finally gets FDA approval to market a drug that has cost $1B or more to bring to bring to market. And of that, according to a recent report of Forbes, over 90% of the total development cost can be in Phase III (final) testing alone! Enter the for-profit medical insurance companies, and suddenly it's very easy to deny coverage for a procedure that might require a week's hospitalization, sometimes utilizing an ICU. All it takes is to adopt the position that they will approve only those procedures supported by the "best medical evidence," which means the equivalence of Phase III resting, even if the drug at issue has long been approved by the FDA for other uses. And if the money isn't there to do the large scale testing these standards mandate, gosh, that's too bad. See, generally, Evidence-based medicine -Wikipedia article , at Section 6, Limitations and criticism.

All that said, I have to hope that the work of Drs. Buckenmaier et al, will pay off and be published in a major journal, such as Pain, and will have the effect of bringing the civilian practice of pain medicine in the U.S., notwithstanding their kicking and screaming, at last into the 21st Century, and on account of which, fresh cases of CRPS will gradually atop entering the system. At which point, the remaining attention of CRPS practitioners will necessary be focused on the remaining patient, with “old and cold” cases. And how that will be accomplished is necessarily the subject of later threads. That said, at least over the next decade, my guess is that the greatest amount of progress will be made in the fields of neuromodulation, but that remains to be seen.

Mike