Six weeks ago I posted on the apparent high quality of the research combined with an avowedly entrepenurial bent at the Stanford Pain Center http://paincenter.stanford.edu/ overseen by by Sean Mackey, MD, PhD, Chief, Pain Management Division. (Post # 10 (10.01.09) to the thread "I feel lost and alone after the specialist appointment" at http://neurotalk.psychcentral.com/thread104385.html)

So imagine my surprise when running Dr. Mackey's nmae through PubMed earlier today, and comming across one for the ages, which I either overlooked or had not been indexed at the time of my previous post:

Sympathetic block with botulinum toxin to treat complex regional pain syndrome, Carroll I, Clark JD, Mackey S, Ann Neurol. 2009 Mar;65(3):348-51, free full text at http://www.ncbi.nlm.nih.gov/pmc/arti...ihms140157.pdf

Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA 94304-1573, USA. irc39@pain.stanford.edu

Abstract
Complex regional pain syndrome is a refractory pain condition with few tested therapies. We hypothesized that botulinum toxin A (BTA) would prolong analgesia after sympathetic blocks in patients with complex regional pain syndrome. We compared the duration of standard lumbar sympathetic block (LSB) with bupivacaine to LSB with bupivacaine and BTA in nine patients with refractory complex regional pain syndrome. Median time to analgesic failure was 71 (95% confidence interval, 12-253) days after LSB with BTA compared with fewer than 10 days (95% confidence interval, 0-12) after standard LSB (log-rank, p < 0.02). BTA profoundly prolonged the analgesia from sympathetic block in this preliminary study.

PMID: 19334078 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/1...m&ordinalpos=6

In the article, the authors explain how this unfunded pilot study took just under three years to recruit 9 subjects who met the author's rigidi includion criteria (essenetially people who had had lower extreimty CRPS-1 for at least six months, failed other therapies, and yet still had at least a 50% reduction im pain, lasting 4 or more hores to conventional sympathetic blocks) and while they hade been hoping for ten subjects, they finally cut it off at 9. And of those 9, only 7 of the subjects could be used in the end. Yet out of the 7, statistically significant results were obtained:

Primary End Point—The rate of pain return was significantly lower after LSB with BTAcompared with local anesthetic alone (Fig 1). Median time to analgesic failure was 71 (95% confidence interval, 12–253) days after LSB with BTA compared with fewer than 10 days (95% confidence interval, 0–12) among those receiving local anesthetic alone (log-rank, p < 0.02).

Secondary End Point—Botulinum toxin–enhanced sympathetic blockade was significantly more effective at reducing VAS pain scores over time than bupivacaine alone. Assignment to the BTA-enhanced LSB was associated with a mean decrease in VAS of 1.6 points (95% confidence interval, 1.2–2.0; p < 0.0001). However, among the more robust responders, the effect size was much larger (Fig 2).

Adverse Events—One patient experienced significant nausea and emesis that started 5 hours after her BTA injection and lasted 2 days; it resolved spontaneously.

http://www.ncbi.nlm.nih.gov/pmc/arti...ihms140157.pdf manuscript page 3.

The authors then go on to note, in part, that:

This study presents preliminary evidence that BTA-supplemented sympathetic blocks may represent a significant novel therapeutic modality for the treatment of sympathetically maintained pain in patients with highly refractory CRPS. Within the context of the otherwise limited options for patients with refractory CRPS, these findings are striking. The small number of patients in this study should be noted. A larger study is now warranted to further test the safety and efficacy of this procedure.

Botulinum toxin is generally understood to be primarily, if not exclusively, a potent inhibitor of release of acetylcholine from cholinergic nerves. This inhibition is long lasting but not permanent, and it does not result in cytotoxicity or neural loss. Inhibition of sympathetic nerve transmission at cholinergic sympathetic ganglia in the lumbar sympathetic chain may be
the mechanism of analgesia. [Citation omitted.]

Id.

So what's the Stanford UGLY? Something that appreared in the htlm copy of the article, but inexplicably didn't make it to the pdf file I've shared with you. Immediately after the Conclusion and before the References, the html copy has the following:

Footnotes

Potential conflict of interest: The authors report filing a patent for the use of botulinum toxins in sympathetic block.

Additional Supporting Information may be found in the online version of this article. [Empahsis added.]

http://www.ncbi.nlm.nih.gov/pmc/arti...ool=pubmed#FN3

Here the good doctors come up with this potentially useful technique and then they patent it, so that anyone elese who uses it has to pay them an agreed royalty. Fortunately, the whole question of the ability to patent "processes" is currently before the Supreme Court. See, The Supreme Court, Process Patents, and Medical Innovation, Aaron S. Kesselheim, M.D., J.D., M.P.H, New England Journal of Medicine http://content.nejm.org/cgi/content/...9658?query=TOC November 18, 2009 (10.1056/NEJMp0909658):

On November 9, the U.S. Supreme Court heard oral arguments in Bilski v. Kappos, one of the most closely watched cases in the Court's current term. The central question involves the legitimacy of a patent on a method for hedging risk in commodities trading, but the outcome will have important implications for health care delivery and research. Although patents covering medicines, devices, and research targets such as DNA sequences have become commonplace, in recent years there has been a surge in new patents on medical processes. Patents have been awarded for processes such as making diagnoses, performing surgery, making prescribing decisions, and other methods for treating patients and engaging in research. The Bilski case represents the first time in nearly three decades that the Supreme Court has considered the standard for issuing process patents. . . . [Footnote omitted.]

You can read the transcript of the Court's November 9, 2009 oral argument here:http://www.supremecourtus.gov/oral_a...pts/08-964.pdf What struck me in reading the transcript was that the government, which had won earlier when the lower appellate court had thrown out the patent, was (through its counsel) pretty well battered about by the Supreme Court, even though they didn't have any sympathy for the position of the would-be patent holder, suggesting that it would be unlikely for it to state a rule that would have broad ramifications, e.g., in the biomed world. For an extensive commentary to that effect, see, http://acslaw.org/node/14771 On the other hand, it could order the case re-argued, specifying the proposed (new) test it wished the parties to address, much as it did in the campaign financing case that was just reargued in September. We shall see.

Mike