[fmichael]

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