Thanks to Pfizer's getting caught in 2004 promoting the off label use of Neuronton, including "promot[ing]and prescrib[ing] the drug for everything from ADHD, mental illnesses to a variety of pain conditions, including migraine headaches" http://www.ahrp.org/infomail/04/05/16.php and a lot of folks - me included - have have side effects from taking large doses, the drug has fallen into widespread disfavor: Neurotten, etc.

Yet, there remains evidence in the real scientific literature that Neurontin (gabapentin) may have beneficial effects in the ttreatment of CRPS. See, "Pharmacologic Management of Complex Regional Pain Syndrome," Michael C. Rowbotham, MD [Director, UCSF Pain Clinical Research Center and Clinical Professor of Neurology and Anesthesiology at UCSF]. Clin J Pain Volume 22, Number 5, June 2006, 425-429 at 427:

One of the first literature reports to describe the efficacy of gabapentin was a case series of CRPS patients.37 The drug has safety advantages over tricyclic antidepressants and has shown evidence of analgesic efficacy in human experimental pain models and for postoperative pain.38,39 There are no data to suggest that gabapentin doses should be different for CRPS compared with chronic neuropathic pain. Other anticonvulsants have received less study for CPRS, although essentially all of them have been used in individual patients with CRPS.

37. Mellick GA, Mellick LB. Reflex sympathetic dystrophy treated with gabapentin. Arch Phys Med Rehabil. 1997;78:98–105.
38. Dirks J, Fredensborg BB, Christensen D, et al. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology. 2002;97:560–564.
39. Dirks J, Petersen KL, Rowbotham MC, et al. Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization. Anesthesiology. 2002;97:102–107.

Free full text at: http://www.rsds.org/2/library/articl...mgnts_crps.pdf

With this in mind. I took a look at my recent own use of Neurontin, where I long ago realized that I couldn't tolerate the side effects of the 2,400 mgs. a day my neurologist had me on (I was in a stupor) and realized that it was working well for me in one respect in particular, when I felt the presence of what my doctors told me - based on my description - was "neurological recruitment" or "wind-up" in the affected limb, when there's a sense of perhaps pulsing but pain hasn't set in yet, and yet you know that means the storm is on the way. It's at that point that I take 600 mg. of Neurontin along with a .5mg Xanax seems to keep things in at bay, at least for a while. (I also take another 600 at night, in part, to help me get to sleep, but that's another matter.)

So I decided to take a look at "wind-up" and came up with with something that makes some sense.

Of course, "wind up" turns out to be anything but benign in the long run. See, “Phosphatidylinositol 3-Kinase Is a Key Mediator of Central Sensitization in Painful Inflammatory Conditions,” Sophie Pezet, et al, J Neuroscience, 2008 April 16; 28(16): 4261-70 at 4267 (phosphatidylinositol 3-kinase (PI3K) is a key player in the establishment of central sensitization, the spinal cord phenomenon associated with persistent afferent inputs and contributing to chronic pain states):

Wind-up in the spinal cord is a phenomenon whereby repetitive stimulation of deep dorsal horn WDR neurons induces an increase of their evoked responses and postdischarge with each stimulus ["Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following C fibre stimulation," Dickenson AH, Sullivan AF Neuropharmacology, 1987; 26: 1235–1238]. This form of spinal plasticity is NMDA-dependent, as is LTP [long-term potentiation], and seems to be the neuronal correlate of pain hypersensitivity. Despite being a fast-onset and short-lasting phenomenon, wind-up may contribute to long-term changes in the spinal cord leading to central sensitization as is produced by peripheral formalin injection ["Evidence for spinal N-methyl-D-aspartate receptor involvement in prolonged chemical nociception in the rat," Haley JE, et al, Brain Research, 1990, 518: 218–226].

Free full text at: http://www.jneurosci.org/cgi/content/full/28/16/4261#B1

All of which brings us to an insightful article that appeared a couple of years ago in the Journal of Neuroinflamation, “The antinociceptive effect of systemic gabapentin is related to the type of sensitization-induced hyperalgesia,” M Mar Curros-Criado and Juan F Herrero, 2007; 4: 15. The abstract follows:

Background

Gabapentin is a structural analogue of gamma-aminobutyric acid with strong anticonvulsant and analgesic activities. Important discrepancies are observed on the effectiveness and potency of gabapentin in acute nociception and sensitization due to inflammation and neuropathy. There is also some controversy in the literature on whether gabapentin is only active in central areas of the nervous system or is also effective in the periphery. This is probably due to the use of different experimental models, routes of administration and types of sensitization. The aim of the present study was to investigate the influence of the spinal cord sensitization on the antinociceptive activity of gabapentin in the absence and in the presence of monoarthritis and neuropathy, using the same experimental protocol of stimulation and the same technique of evaluation of antinociception.

Methods

We studied the antinociceptive effects of iv. gabapentin in spinal cord neuronal responses from adult male Wistar rats using the recording of single motor units technique. Gabapentin was studied in the absence and in the presence of sensitization due to arthritis and neuropathy, combining noxious mechanical and repetitive electrical stimulation (wind-up).

Results

The experiments showed that gabapentin was effective in arthritic (max. effect of 41 ± 15% of control and ID50 of 1,145 ± 14 micromol/kg; 200 mg/kg) and neuropathic rats (max. effect of 20 ± 8% of control and ID50 of 414 ± 27 micromol/kg; 73 mg/kg) but not in normal rats. The phenomenon of wind-up was dose-dependently reduced by gabapentin in neuropathy but not in normal and arthritic rats.

Conclusion

We conclude that systemic gabapentin is a potent and effective antinociceptive agent in sensitization caused by arthritis and neuropathy but not in the absence of sensitization. The potency of the antinociception was directly related to the intensity of sensitization in the present experimental conditions. The effect is mainly located in central areas in neuropathy since wind-up was significantly reduced, however, an action on inflammation-induced sensitized nociceptors is also likely.

Free full text at: http://www.jneuroinflammation.com/content/4/1/15

And in cases of chronic CRPS, central sensitization remains the name of the game. See, e.g., "Ketamine as an adjuvant in sympathetic blocks for management of central sensitization following peripheral nerve injury," Rani A Sunder et al, Journal of Brachial Plexus and Peripheral Nerve Injury,
Vol. 3, epub 25 October 2008, free full text at http://www.jbppni.com/content/3/1/22 ; "Cortical reorganization during recovery from complex regional pain syndrome," Christian Maihöfner, CA, MD et al, Neurology, 2004 Aug 24; 63(4): 693-701:

OBJECTIVE: To characterize reorganization of the primary somatosensory cortex (S1) during healing process in complex regional pain syndrome (CRPS).

BACKGROUND: Recently, the authors showed extensive reorganization of the S1 cortex contralateral to the CRPS affected side. Predictors for these plastic changes were CRPS pain and the extent of mechanical hyperalgesia. It is unclear how these S1 changes develop following successful therapy.

METHODS: The authors used magnetic source imaging to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 10 patients during a year or more of follow-up.

RESULTS: Cortical reorganization reversed coincident with clinical improvement. A reduction of CRPS pain correlated with recovery from cortical reorganization.

CONCLUSIONS: Changes of the somatotopic map within the S1 cortex may depend on CRPS pain and its recovery.

PMID: 15326245 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

That said, I still don’t know if one can reliably take Neurontin just on the first sign of trouble – my neurologist had initially told me that one had to maintain a constant dosing - all I can say is that it seems to help me keeping "attacks" somewhat at bay, especially after I've been too active for my own good.

Mike

Yes but does the neurontin take away your rsd pain?

It didn't for me and all I was left with was the nasty side effects of being left in a zombie like stupor along with the rsd pain. At least I could return to work and drive when I went off that class of drugs even if I did have to deal with the pain.

You may be able to keep the monster at bay for a time as you have admitted, but what you are doing is called a drug cocktail and that has not been proven scientifically in controlled clinical studies, or has it?

Not to mention all of the other potential interactions and side effects that go along with that. I know we all have to make choices and trade offs with rsd, mine was to stay in the game as long as I possibly could.

The other question I have is how is this scientific literature any more "real" than that of Rueban's work that was once the corner stone on which all well intending doctors made medical decisions about their patients health?

Chronic pain is on that list of off label uses promoted by Pfizer, RSD /crps is simply a sub category of that.

I'm not anti-pharmaceutical, god knows I need help too. But I am more cautious and I think as patients we need to be much more diligent and ask our doctors for much more proof before we simply fill and take the prescriptions we are given.

MsL

Dear Mslday -

As the Reuban case has taught us, it is difficult to specify what level of scientific certainty you would wish to impose on a physician's use of medications. The whole thing about contaminating multi-center project. (Anyone know for sure why the Thalidomide study hasn't been published yet, 3 years after it completed the recovery of data from over 20 locations?) Personally, I like the idea of doing thing the old fashioned way. One guy does a study and publishes. The next tries to see if he can invalidate the results of the first, and publishes in any event.

Seriously, I am mindful of when JPL builds satellites, it checks out the computer's chips so rigorously that come launch date, they can be 4+ years behind whatever the commercial world is doing.

Mike

PS to my last:

I realized I didn't answer one of your fundamental questions. Does the stuff really work? My sense is that is truly softens the blow when you can feel things building at a point when you're not yet in serious pain. That said, it doesn't put out the fire once it's really cooking. But it dampens things down a bit, at the cost of making me pretty tired if I took it all day long.

And not only is it only one of many drugs I throw at this every day, it's hard to say whether I regard it as being part the central core. And it's true that nothing short of heavy analgesics "works" in terms of really taking the pain away once it's underway. And fortunately, my liver and kidneys don't seem to mind all of the extra duty, except there was that one incident when I was ordered off Trileptal overnight, without an immediate replacement, when my blood sodium levels dropped sharply over six weeks, whereupon the cramping got so out of control that I was having scalp cramps, which were only assuaged by my inrtoduction to Neurontin in the first place. (And did it help!) But now Baclofen (50 mg./day) seems to do most of the heavy lifting in the spasm dept.

I know it seems as though I'm being equivical. It's just a matter of trying to express the utility of something that is - in my experience - better than nothing, when taken in moderation.

Neurontin (Gabapentin) is no use for rsd in my experience, even from my begining docs have always tried to fall back on it with the use of Oxycontin, Dialaudid, lyrica and tramodal and all the other pain meds u can think of.
Dosage of Neurontin was 3-300mg pills 3 times a day. so in a day 2700mg and guess what it does zip i could have believed a glass of water was going to help my pain just as much as this worthless drug, never got any side effects its just plain worthless.

One can work with NMDA receptors. Magnesium is useful for this and also is a good vasodilator.

Here is a wiki article that lists drugs that work as antagonists:

http://en.wikipedia.org/wiki/NMDA_receptor

Avoidance of MSG (monosodium glutamate) may help and avoidance of aspartic acid (in nutrasweet and some supplements) may help too. These two amino acids stimulate the NMDA receptors. MSG is in many processed foods, especially soups and snacks, gravies, etc. Restaurants use it heavily.
Q-doba mexican really pours it on....I can't eat there. Some new soups are on the market as NO MSG...and the difference is striking to the body! I have met people who eat MSG containing foods 3 or more times a day! We are just not designed to handle a flood of non protein bound glutamate this way. We were designed to consume glutamate that is normally in foods which is slowly cleaved off the carriers as needed.

MSG and NMDA receptor stimulation is a very common trigger for peripheral neuropathy. I've posted many many times on this subject over there. I am finding many similarities to PN while reading here. We have several posters with full body burning, for example.

I am new here and all of this information is mind blowing. I have had TOS for 10 years and just diagnosed with RSD last month. I have been taking percocet for the pain and recently neuronting. Absolutely no help from neurontin, that I have seen. I am only on 600 mg per day so far. My pain has spread and gotten consistently worse. Thank you for all the information. I am very interested to see how I should proceed with this diagnosis. Linda

My Pain Management Doctor put me on Gabapentin (Neurontin) just after I was diagnosed with RSD and I too, don't think that it helped. If anything, I think it made me worse as I had to deal with even more fatigue than normal. The RSD spread from my left leg to my right arm whilst I was on the Neurontin so I personally, don't feel that it can 'put a spread to a halt or prevent it from happening altogether'! As we all know, RSD will do whatever it wants, when it wants.

It is an interesting article though - thank you for sharing it with us all. I have spoken to some people who have had positive results from the Neurontin so I guess everyone of us with RSD is different and no two people react the same!

I agree with the comments that have been posted here: Neurontin helps some people more than others and, more importantly, helps in some ways more than others. Does anyone else experience the "wind-up" sensations that I addressed in the initial posting?

mrsD, as for as the value of NDMA antagonists, I too have posted a lot on that over the years. I'm currently on 30 mg. of Memantine a day in an attempt to slow down the loss of grey matter in the brain that is incident to chronic pain, and it has done nothing for my CRPS, despite at least one published case report showing that six patients with CRPS had statistically significant results in pain reduction from the same dose of Memantine. See, "Memantine Treatment of Complex Regional Pain Syndrome: A Preliminary Report of Six Cases," Nektarios Sinis at al, Clin J Pain, 2007, Vol. 23, No. 3, March/April 07 237-243, a copy of which is attached. But I wasn't surprised, having been personally advised by a top CRPS researcher in 2003 that doses of Memantine that people were talking about were too low to make a difference in cases of CRPS, and that ketamine was where the action was. Unfortunately, due to a pre-existing history of glaucoma, I was disqualified from the high dose German ketamine trials later that year, with airline tickets already in hand.

However, even the high dose ketamine trials could report only generally favorable but mixed reports on improvement in quality of life six months out, while the same authors' study of "low dose" ketamine infusions (increasing over 10 days to 500 mg/day) showed no significant benefit in terms of pain relief even at the end of the 10 day infusions. Compare, "Efficacy of Ketamine in Anesthetic Dosage for the Treatment of Refractory Complex Regional Pain Syndrome: An Open-Label Phase II Study," Kiefer RT, Rohr P, Ploppa A, et al, Pain Med., 2008 Feb 5, free full text at http://www.rsds.org/2/library/articl...a_Dietrich.pdf, with, "A Pilot Open-Label Study of the Efficacy of Subanesthetic Isometric S(+)-Ketamine in Refractory CRPS Patients," Kiefer RT, Rohr P, Ploppa A, et al, Pain Med. 2008; 9(1):44-54, free full text at http://www.rsds.org/2/library/articl...ohr_Ploppa.pdf. And I suppose that knowing I couldn't get into a high dose ketamine treatment was what sent me off in search of RUL ECT as a treatment for CRPS, only to later discover find out that due to decades old restrictions, it was illegal in California, outside an IRB supervised clinical trial. (For anyone interested in my efforts in that regard, check out the thread at http://neurotalk.psychcentral.com/thread42529.html Unfortunately, the link to my review article on the JPPM site is no longer active, but it's available on the RSDSA server at http://www.rsds.org/2/library/articl...haels_CRPS.pdf)

All that said, I greatly appreciate the information concerning diet and NDMA. Thank you!

Mike

Attached Files

Memantine Treatment of Complex Regional Pain Syndrome - Sinis et al - Clinical Journal of Pain 2.pdf (149.4 KB, 619 views)

Hi Mike!

Very interesting stuff. I believe I experience what your calling wind up. It seems I can feel/tell the storm of pain is approaching, and sometimes by the way it feels I can tell if it is gonna be a F5 opposed to a F1 type of pain.

I recently have been put back on neurontin, and the last week or so I have been awakened by some pretty mean nightmares. Yesterdays nightmare had me feeling like my life had changed for the worse all day, even though I knew it was a nightmare and not real, it traumatized me in some weird way.

So the next time I get to see the pain doc, im gonna tell him I want off the nightmare train. I am getting to the point where I would rather suffer than have all these weird side effects. Just using pain meds, and my instinct on what to do or not do activity wise to keep my pain in the "I can handle it arena".

Pain can get to runaway levels, but with moderation in activity, and a few pain meds, I can get it down a couple of notches into a level that I can at least cope.