Fibromyalgia Support Group

Yes that sounds like nerves...I get ice picks and bee sting like pain in my hips. The neurontin is supposed to help with that - I am not on it as I am on so many meds for RA already! I use ice packs when I can which seems to help

hugs and prayers!

How's your circulation?

I have peripheral neuropathy and I get those kinds of sensations. I also get an icy hot, burning sensation on the bottoms of my feet.

I started taking D-Ribose a few weeks ago and have noticed that lot of these sensations have lessened or even disappeared. I was even able to stop taking Requip - for RLS - and I had it bad.

Hawthorne berry has been recommended for circulation and lower blood pressure and I plan to try that soon.

There's also carpal tunnel. You might google that and see how your wrists and arms are put together and how the nerves get crimped in their little tunnels.

Changing your habits and a few exercises can make an amazing difference.

Neurontin, as well as Lyrica, stops the creation of new neural pathway synapses. This is like a death sentence for your brain. Synapses will die (as is natural) but no new synapses will be created. Consider anything else, eh? You're way too young to be killing off your brain.

is that proven?? about the bran??i mean this stuff seems to really be helping.. a few weeks ago i had to have help to walk across the room.. i had to use the walls and door jams to get around on my own..i had to literally hold on to and lean on the stove to try to cook dinner.. now im walking and moving.. there is pain but i am not so weak..id hate to give that up

Icepicks, bee stings, knife stabbing, frostbite in the fingers.......those describe perfectly the terrible nerve pain that I have been having lately. I can usually keep it under control with Nuerontin (Gabapentin), but lately even that isn't working.

It has been so bad the last few days that it has kept me off the board. So sorry to hear you are going thru this too. I hope you feel better soon.

unduki, I think you're intentionally scaring the folks who are most prescribed and are most helped by Nuerontin and Lyrica.

The person who is quoted in your article on brain synapses is a nutritionist, not a doctor. I'm not saying he is not correct, I don't know enough to say that. But I think unless you have a more compelling argument in regards to this theory then there is no need to unduly upset some people in desperate search for relief of these horrific symptoms.

I must say it scared me the comment on the brain synapses?....i thought holly shit,im a gonna for sure ,cos i cant take neurontin or Lyrica.....anyway huggs to all..

Hi Gingye! I'm sorry you're having the awful sharp pain sensations & hopefully you'll have answers & effective treatment really soon. I may have some of the same type sensations, but not nearly to the extent that you're describing. I don't yet have any suggestions for you, except of course to talk with your doc for sure. I'll keep my fingers crossed for ya, that your doctor will know what this is & can help you! Will you keep us posted?

Unduki, Since I do know that Lyrica and Neurontin are 2 very commonly prescribed meds for fibro / nerve pain, I'd be very interested in any links you could post that back up what you say about the brain damage side effect. Thanks in advance.

This is the study unduki refers to
and although they are more concerned with the brain of the unborn child I would be concerned about what it's doing to my brain being that it is slower to regenerate would I want something that is going to stop it or make it any slower

Study Title:
Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis
Study Abstract:
Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS synapse formation as α2δ-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of α2δ-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. α2δ-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to α2δ-1 and powerfully inhibits excitatory synapse formation in vitro and in vivo. These findings identify α2δ-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation.

From press release:

Researchers at the Stanford University School of Medicine have identified a key molecular player in guiding the formation of synapses — the all-important connections between nerve cells — in the brain. This discovery, based on experiments in cell culture and in mice, could advance scientists’ understanding of how young children’s brains develop as well as point to new approaches toward countering brain disorders in adults.

The new work also pinpoints, for the first time, the biochemical mechanism by which the widely prescribed drug gabapentin (also marketed under the trade name Neurontin) works. “We have solved the longstanding mystery of how this blockbuster drug acts,” said Ben Barres, MD, PhD, professor and chair of neurobiology. The study shows that gabapentin halts the formation of new synapses, possibly explaining its therapeutic value in mitigating epileptic seizures and chronic pain. This insight, however, may lead physicians to reconsider the circumstances in which the drug should be prescribed to pregnant women.

The paper, to be published online Oct. 8 in the journal Cell, looks at the interaction between neurons — the extensively researched nerve cells that account for 10 percent of the cells in the brain — and the less-studied but much more common brain cells called astrocytes. Much work has been done on how neurons transmit electrical signals to each other through synapses — the nanoscale electrochemical contact points between neurons. It is the brain’s circuitry of some 100 trillion of these synapses that allow us to think, feel, remember and move.

It is commonly agreed that the precise placement and strength of each person’s trillions of synaptic connections closely maps with that person’s cognitive, emotional and behavioral makeup. But exactly why a particular synapse is formed in a certain place at a certain time has largely remained a mystery. In 2005, Barres took a big step toward explaining this process when he and his colleagues discovered that a protein astrocytes secrete, called thrombospondin, is essential to the formation of this complex brain circuitry.

Still, no one knew the precise mechanism by which thrombospondin induced synapse formation.

In this new study, Barres, lead author Cagla Eroglu, PhD, and their colleagues demonstrate how thrombospondin binds to a receptor found on neurons’ outer membranes. The role of this receptor, known as alpha2delta-1, had been obscure until now. But in an experiment with mice, the scientists found that neurons lacking alpha2delta-1 were unable to form synapses in response to thrombospondin stimulation.

And when the researchers grew neurons in a dish that were bioengineered to overexpress this receptor, those neurons produced twice as many synapses in response to stimulation with thrombospondin than did their ummodified counterparts.

The new discovery about alpha2delta-1’s key role in synapse formation carries important implications for understanding the cause of pain and of epilepsy and developing improved medications for these conditions.

It was already known that alpha2delta-1 is the neuronal receptor for gabapentin, one of the world’s most widely administered medications. Gabapentin is often prescribed for epilepsy and chronic pain, and its off-label use for other indications is widespread. Up to now, the molecular mechanism of gabapentin’s action — what, exactly, it’s doing to counter seizures or chronic pain — was unknown. But both syndromes may involve excessive numbers of synaptic connections in local areas of the brain.

In their new study, Barres and his colleagues found that when gabapentin was administered in developing mice, it bound to alpha2delta-1, preventing thrombospondin from binding to the receptor and, in turn, impeding synapse formation. Likewise, by blocking thrombosponin, gabapentin may reduce excess synapse formation in vulnerable areas of the human brain.

Barres noted that he and his colleagues found that gabapentin does not dissolve pre-existing synapses, but only prevents formation of new ones. That greatly diminishes gabapentin’s potential danger to adults. In mature human brains, astrocytes ordinarily produce very little thrombospondin, and adult neurons don’t form many new synapses, although some new synapses do continue to be formed throughout life — for example, in a part of the brain where new memories are laid down and at sites of injury to neurons, such as occurs after a stroke.

But the new findings raise questions about gabapentin’s effect in situations where synapse formation is widespread and crucial, most notably in pregnancies. The vast bulk of the brain’s synapses are formed during gestation and the very early months and years after birth. Because gabapentin easily crosses the placental barrier, it could potentially interfere with a fetus’ rapidly developing brain just when global synapse formation is proceeding at breakneck speed.

“It’s a bit scary that a drug that can so powerfully block synapse formation is being used in pregnant women,” Barres said. “This potential effect on fetal brains needs to be taken seriously. Right now, doctors have the view that gabapentin is the safest anticonvulsant. There is no question that pregnant women with epilepsy who have been advised by their neurologists to continue their anticonvulsant treatment with gabapentin during their pregnancy should definitely remain on this drug until instructed otherwise. But there is no long-term registry being kept to track gabapentin-exposed babies. Our findings are saying that we need to be following up on these newborns so that their cognitive performance can be studied as they grow older.”


Study Information:
Çagla Eroglu, Nicola J. Allen, Michael W. Susman, Nancy A. O'Rourke, Chan Young Park, Engin Özkan, Chandrani Chakraborty, Sara B. Mulinyawe, Douglas S. Annis, Andrew D. Huberman, Eric M. Green, Jack Lawler, Ricardo Dolmetsch, K. Christopher Garcia, Stephen Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis Cell 2009 October
Stanford University School of Medicine.

Duly noted. Thank you Mary.

This study that was released earlier this month in no way suggests that everyone who is on this drug stop taking it immediately. If you are concerned about it, take it to your doctor for discussion. It might be like Avandia or other drugs where the benefits outweigh the risks.

Here is more info with web site to refer to.

http://www.medpagetoday.com/Neurol...


Inhibiting Synapse Formation May Be Mechanism of Antiseizure Drug
By Kristina Fiore, Staff Writer, MedPage Today
Published: October 08, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
for reading medical news
Action Points

* Explain that new research shows the interaction between thrombospondin and the receptor α2δ-1 likely plays a role in new synapse formation.


* Explain that gabapentin may work by binding to α2δ-1 and inhibiting the interaction between the receptor and thrombospondin.


* Note that the exact mechanism of action of gabapentin was previously unknown.

Gabapentin (Neurontin) may work by blocking the formation of new synapses, researchers say.

In a mouse model and in vitro, researchers found that neurons lacking the receptor α2δ-1 couldn't form new synapses, while those that overexpressed the protein produced twice as many synapses as their unmodified counterparts, according to Ben A. Barres, MD, PhD, of Stanford University, and colleagues.

Gabapentin, used to treat neuropathic pain and epilepsy, binds to and inhibits α2δ-1 -- but no one was sure of the exact molecular mechanism of the drug's action before this research, they wrote in the Oct. 8 issue of Cell.

While the molecules that regulate the formation of synapses remain poorly understood, research has shown that thrombospondin -- an astrocyte-secreted protein -- promotes central nervous system synaptogenesis. Still, the mechanism by which it induced synapse formation was unknown.

The researchers said thrombospondin may bind to α2δ-1, which was originally isolated from skeletal muscle as a nonessential subunit of the L-type calcium channel complex.

The receptor also has a large extracellular region that contains a well-known protein-protein interaction fold: the Von Willebrand Factor A (VWF-A) domain. That suggests it could serve as a receptor for extracellular ligands, the researchers said.

To test their hypothesis, they conducted both in-vitro and mouse model analyses.

In vitro, they found that thrombospondin bound directly to α2δ-1 and mediated its synapse-inducing activity.

They saw that thrombospondin binding to the VWF-A domain of α2δ-1 caused a structural rearrangement of the molecule, triggering subsequent "conformational shifts in its binding partners" and switching the molecule to an "active" state.

This, in turn, led to signaling events that triggered the recruitment of synaptic adhesion, they said.

They also saw in vitro that neurons engineered to overexpress α2δ-1 produced twice as many synapses in response to stimulation with thrombospondin as unmodified receptors.

In the mouse model, the researchers found that neurons lacking α2δ-1 couldn't form synapses in response to thrombospondin stimulation.

And when mice were given gabapentin, it bound to α2δ-1, preventing thrombospondin from binding to the receptor and cutting off synapse formation.

These findings suggest that gabapentin blocks synapse formation by interfering with the thrombospondin and α2δ-1 interaction.

"Gabapentin binding to α2δ-1 restricts the conformation of the VWF-A domain and keeps the molecule in its 'inactive' state," the researchers said. This "inhibits activation of the synaptogenic signaling complex."

Therefore it's "possible that inhibition of excitatory synapse formation is an important mode of its therapeutic action in epilepsy and pain," they said, adding that "aberrant excitatory synaptogenesis may contribute to the pathophysiology of neuropathic pain and epilepsy."

Barres noted that gabapentin doesn't dissolve preexisting synapses -- it only prevents the formation of new ones.

He said the findings raise questions for pregnant women, since the bulk of the brain's synapses are formed during gestation and the early months and years after birth.

"It's a bit scary that a drug that can so powerfully block synapse formation is being used in pregnant women," Barres said. "This potential effect on fetal brains needs to be taken seriously."

Future research should follow-up on newborns whose mothers take gabapentin to assess their cognitive performance as they grow, he said.

Barres added that other studies should investigate whether thrombospondin and α2δ-1 are involved in formation of synapses in the neuromuscular junction, since they are so highly concentrated in this location, and they should investigate whether other α2δ family members also regulate synapse formation.

The study was supported by grants from the National Institute of Drug Addiction, the National Heart, Lung, and Blood Institute, the National Institutes of Health.

The researchers reported no conflicts of interest.

Primary source: Cell
Source reference:
Eroglu C, et al "Gapapentin receptor α2δ-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis" Cell 2009; 139(2): 4791.

I have horrible ice pick pain in my knees for months now, like you , had to , well still have to use walls to walk, even a walker. I also have steroid myopathy which brought this whole thing on though. I am prayin the neurontin will help me ,on week five so far nothing major but keeping fingers crossed. This fibro sucks! i was so active befoe this hit me as far as walking, gym etc