We are all too aware of the suffering of everyone who has exhausted every therapy and remains in intractable pain, or worse, so I've been looking to see what may be available on the short-to-medium-term horizon.

One of the things that the landmark study, 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, Epub 2010 Mar 24, FULL ONLINE TEXT @ http://www.rsds.org/2/library/articl..._Pain_2010.pdf explained rather nicely was why and how it is that Deep Brain Stimulation (DBS) has been effective in CRPS. Unfortunately (or not in light of possible SERIOUS side effects) DBS for the treatment of pain was banned outside of experimental studies by the FDA in the mid-1980's. Nevertheless, it is approved from the treatment of dystonia and other movement disorders, there it is. And because it's approved for dystonia, etc., it can be done on an "off-label" basis: good luck getting insurance companies to pay for off-label neurosurgery!

Further, the same underlying mechanism, also explains for the first time why electro-shock from various sources actually works in CRPS, right down to the cellular level. For one of the many articles chronicalling the effectiveness of ECT, despite the fact that it's mechanism was "unknown," see, e.g., Treatment of CRPS with ECT, Wolanin MW, Gulevski V, Schwartzman R, Pain Phys. 2007;10:573-578 FULL ONLINE TEXT @ http://www.rsds.org/2/library/articl...chwartzman.pdf

But with ECT, the problem is that, even with the newer and safer "high dosage RUL ECT delivered with an ultra-brief stimulus" (The Cognitive Effects of Electroconvulsive Therapy in Community Settings, Sackeim HA, Prudic J, Fuller R, et al., Neuropsychopharmacology 2007; 32:244-254), the fact remains that there is no money to pay for the large scale studies necessary to obtain FDA approval of RUL ECT for CRPS. Quite simply because, to the medical device industry, having a few thousand CRPS patients using its ECT equipment would be a drop in the bucket, not worthy of investing in new studies. And as a result, without a "co-morbid" Dx of otherwise untreatable depression, insurance carriers won't pick that one up either.

I am however pleased to announce that a new contender has entered the building, if not the arena:

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, Epub 2009 Sep 29, FULL ONLINE TEXT @ http://www.rsds.org/2/library/articl...uiz_Castro.pdf

Unit for Stereotactic, Functional Neurosurgery and Radiosurgery of the Service of Neurology and Neurosurgery and Pain Clinic, General Hospital of Mexico, Mexico City, Mexico. slanfe@prodigy.net.mx

Abstract
Motor cortex stimulation (MCS) is useful to treat patients with neuropathic pain syndromes, unresponsive to medical treatment. Complex regional pain syndrome (CRPS) is a segmentary disease treated successfully by spinal cord stimulation (SCS). However, CRPS often affects large body segments difficult to cover by SCS. This study analyzed the MCS efficacy in patients with CRPS affecting them. Five patients with CRPS of different etiologies underwent a small craniotomy for unilateral 20-grid-contact implantation on MC, guided by craniometric landmarks. Neurophysiological and clinical tests were performed to identify the contacts position and the best analgesic responses to MCS. The grid was replaced by a definitive 4-contacts-electrode connected to an internalized system. Pain was evaluated by international scales. Changes in sympathetic symptoms, including temperature, perspiration, color and swelling were evaluated. Pre-operative and post-operative monthly evaluations were performed during one year. A double-blind maneuver was introduced assigning two groups. One had stimulators turned OFF from day 30-60 and the other from day 60-90. Four patients showed important decrease in pain, sensory and sympathetic changes during the therapeutic trial, while one patient did not have any improvement and was rejected for implantation. VAS and McGill pain scales diminished significantly (p<0.01) throughout the follow-up, accompanied by disappearance of the sensory (allodynea and hyperalgesia) and sympathetic signs. MCS is effective not only to treat pain, but also improve the sympathetic changes in CPRS. Mechanism of action is actually unclear, but seems to involve sensory input at the level of the spinal cord.

PMID: 19793621 [PubMed - indexed for MEDLINE] [Emphasis added: the point is huge!]

http://www.ncbi.nlm.nih.gov/pubmed/19793621 (And note how they can do double blinding simply by turning electrodes off and on, which is a neat trick.)

Finally, for a nice article explaining both MCS and DBS in clear language, check out, Intracranial Neurostimulation for Pain Control: A Review, Robert Levy, Timothy R. Deer and Jaimie Henderson, Pain Physician 2010; 13:157-165, FULL ONLINE TEXT @ http://www.painphysicianjournal.com/...13;157-165.pdf (And for any unknown term, just Google/bing/yahoo the word in question, preceded by "definition.")

That said, it's too bad that Levy et al missed the 2009 article from Velasco et al, when they go on to say:

While many case series have been published on the use of MCS or DBS for pain, no randomized, controlled trials exist to confirm the therapies’ effectiveness. This lack of class I data may cause some observers to view the therapies skeptically in spite of their considerable history of clinical use. MCS is probably better suited to such studies than other forms of neurostimulation, in that effective stimulation evokes no perception on the part of the patient save for pain relief. This presents researchers with a unique opportunity to perform blinded studies in which placebo effects can be assessed. Such studies could employ crossover designs to encourage enrollment and address ethical concerns related to the implantation of leads into control patients.

The lack of randomized controlled trials may be due, in part, to the challenges of patient recruitment and monitoring and the need to assign patients to control groups, which by definition means subjecting patients to treatments that have already been unsuccessful in managing their pain. However, the risk of not performing these studies is great, because it means that both physicians and patients lack definitive information about the efficacy of intracranial neurostimulation therapies. This then will slow the further development of the therapies and limit the access of patients to them in the future.

Little did they know that, in the case of MCS, it was simply a matter of flipping the switches every so often!

Hopefully, industry has now gotten the message and large scale studies (if performed in only a few select locations) will soon be underway.

Mike