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    Targeting GABA Receptors Yields A Step Forward In Pain Therapy
    By News Staff | January 21st 2008 04:43 PM | 3 comments | Print | E-mail | Track Comments
    Our bodies sense painful stimuli through certain receptors located in the skin, in joints and many internal organs. Specialized nerve fibers relay these signals coming from the periphery to the brain, where pain becomes conscious. “The spinal cord is placed between these structures as kind of a pain filter”, says Hanns Ulrich Zeilhofer, Professor at the Institute of Pharmaceutical Sciences at ETH Zurich and at the Institute of Pharmacology and Toxicology of the University of Zurich.

    That filter assures that pain is not evoked by everyday stimuli like light touch. This is accomplished by inhibitory nerve cells located in the spinal dorsal horn that release the messenger molecule-amino butyric acid (GABA) at specialized contacts between neighboring nerve cells, so-called synapses. GABA then activates chloride channels on those neighboring cells which relay the pain signals to the brain.

    In patients with chronic inflammatory diseases, such as rheumatoid arthritis or after nerve damage, for example following injuries, the pain inhibiting action of GABA becomes severely compromised. Pain signals are then conducted to the brain nearly unfiltered. Benzodiazepines, such as the sedative drug Valium®, which enhance the action of GABA, alleviate chronic pain when they are applied directly to the spinal cord via an injection into the spinal canal.

    In practice, however, such injections can only be done in very selected cases. More often benzodiazepines are administered systemically, such as with tablets. In this instance, the benzodiazepines not only act in the spinal cord but also in the brain where they can have undesired, sometimes deleterious, effects on pain patients.

    The drugs cause sedation, impair memory, and can even lead to addiction. In addition, during prolonged treatment their effect often fades with time. Classic benzodiazepines should therefore be avoided in chronic pain patients.

    It had been acknowledged for some time that GABA serves important functions in pain control. That benzodiazepines act on at least four different subtypes of GABA receptors was also known. Nonetheless, these receptors were largely neglected as potential targets for pain treatment.

    The research team led by Ulrich Zeilhofer used genetically altered mice in experiments to target the GABA receptors that control spinal pain relay. They first induced a slight inflammation in one hind paw or irritated the sciatic nerve to induce pain. A few days later the mice received an injection of a benzodiazepine close to the spinal cord. Experiments with the mice allowed the researchers to identify two subtypes of GABAA receptors which mediate spinal pain control.

    For experiments with animals, drugs with the proposed receptor specificity are already available. Such experiments have confirmed that the pharmacological enhancement of spinal GABA receptor function inhibits the relay of pain signals to the brain. Further studies have also shown that these compounds did not lose their analgesic effects during prolonged treatment and did not lead to addiction.

    Successful design of a drug that targets only those two subtypes of GABA re-ceptors would be a big step forward in pain therapy. Chronic pain could be treated specifically and with fewer side effects. “The challenge is now for pharmaceutical companies to develop drugs that specifically target these receptors in humans”, says Zeilhofer.

    Comments

    You are a complete and ignorant fool. Perscribed benzodiazepine use has nearly completely dismantled my CNS and receptors. Everything you mention in this post is nothing short of everyday pain which I never had before benzos. From my first dose I got sicker and sicker over a 3 year period. Trying to withdraw from these drugs has been the most horrific, painful and time consuming thing I could have ever imagined. I havent been able to work for the last 10 months because of horrible protracted withdrawal from being cold turkey'd while in medical supervision. I will add some of my blog entries if you are interested in reading about the severe consequences that can occur from these drugs. And if your really interested, I can put you on about 5000 people who have been adversely affected and have gone through severe suffering and total life altering changes from these poisons.

    This will only scratch the surface in terms of the suffering that myself and many others are enduring...
    This was at about 2-3 months off valium.

    Well its been three months plus and things are pretty nasty on my end so I thought I would open my blog again. In all seriousness I'm a little stunned at the way things are going now and really only had 2-3 decent days since. I'm gonna copy some blog entries on here from janruary till today to get this thing rollin again.

    Its been rough from the get go but lets start in march

    March 21

    Not doing well at all. Pain and suffering has reached near shut down proportions. Absolutely sick and tired of pushing the limits on an empty tank. I need to stabilize NOW... Breathing which cannot be avoided hurts so bad in my chest muscular skeletal system front and back that I can barely stand it. Who can be expected to live like this and function in the real world. By the time this process is complete there wont be anything left and will be starting from ground zero. I have no place to go I MUST WORK. Doctors say I'm fine but I am sicker then imaginable and cannot continue on like this anymore. I have talked to people that have had REAL disease and sickness and they confirmed that there suffering wasnt nearly as bad. I am re thinking all of this as I cannot loose everything I have worked for. i felt so good at 5 mg of valium that I bought a 2008 4x4 in october. It has to be paid for. I can barely stand up now. I must regain functionability ASAP.

    P,S. I miss playing my guitar, fishing., enjoying raceday sunday and GIRLS. I'm absolutely sick of living like a hermit in a cave and so sick that I almost have to crawl because I discontinued a drug...

    March 23

    Just fell asleep at 930 tonite and woke up to insane adrenaline and brutal anxiety at 10 pm. An hour and a half has passed and its still raging. This is criminal...

    March 24

    615am... I woke up trembling and shaking profusely and freezing. I cant do the appointment I'm off to the ER I have reached my limit with this brutality.

    march 24

    Im back and was treated as if I were some street addicted lookin for a fix and when the day was over, I was cut loose to go in the same shape I entered in. Reality is setting in and I'm gonna have to stop working and just tough it out. I never want to have another nite like that agian... Thanks for all the love guys.
    Back to the house I was raised in I go I guess.

    March 25

    Well I dont have to worry about how I'm gonna get through another day at work because I lost my job today. I'm totally gonna try and make this a turning point in my benzo nightmare and make a good situation out of a bad one. I did everything right and worked as hard as I could everyday. When I got the news at lunch it confirmed that my tolerance to stress is near zero as it put me to my knees. I thought I was gonna die I felt so bad. But whats done is done and I guess I need to start packin. Hopefully there wont be much down time on the PC. As usual I hope you all are doing well today.

    March 26

    The thing that amazes me is even though I can rationalize in m mind that I have an opportunity here to get past the biggest hurdle that I have ever been faced with, how come last nite and upon waking now my physical pain level is so high that its not even manageable?!? I mean I may as well have swallowed up a bunch of charcoal briquettes that are glowing red hot and searing my insides. Never felt anything like this not even after my xanax ct and I cant take another second of it. I will begin the moving process today on a low level establishing my sleep quarters and get a modem from the local cable provider so I have my means to cope with all of this. If I feel well enough I will get the truck and complete the move this weekend as its not comfortable here anymore. I can honestly say that in the last ten days I have suffered more then some do in ten years. I hope this breaks just a little bit soon. My birthday is on Thursday and I could care less right now. I remember while I was tapering thinking that I would go out and celebrate my accomplishment a little bit, but now I'm just trying to find the strength to complete the move.

    April 4

    The Song Remains The Same... Every task I do feels like I ran a marathon. My respritory system is compromised nearly around the clock and I'm constantly gasping for air. Every muscle in my torso front and back feels like it is either strained or pulled. My bp runs 85/55 upon resting and I feel like all processes are shutting down. THEN last nite before I fell asleep, then onset of what seemed to be intense adrenaline and stiffness/cramping and severely tightening muscles ravaged my body for about an hour causing feelings that felt like my lungs were collapsing and spasming leaving me suffocated. Only to wake up 6 hours later riddled with back pain and feelings of toxic poisening. I'm done with all of this because I was'nt broken when I decided to taper and now EVERYTHING that was good in life is a distant memory nowhere in sight and I will not endure this kind of suffering any longer. I don't know what the solution is but waiting is not working and I really feel now that my decision to do this was the biggest mistake I ever made in life.

    April 9

    OK guys and gals...
    Heres the scoop. So, I finally went to see this dependency Psych after a full two weeks of tests, labs and imaging done by my GP and internal medicine DR's that concluded I have a clean bill of health. A two and a half hour psych eval was performed today by the Developer of the psychiatric unit of our World Class Cleveland Clinic Foundation. The first hour and a half was conducted by his assistant and upon completion she explained that the man I was about to see is TOP DAWG here in Cleveland and World renowned for his accomplishments. When I walked in the first question he ask me is what I was doing here? At that point the first thing that came to mind was that I had been waisting my time yet again. Although I knew he had reviewed my case I told him exactly why I was there and those of you that read my blog here know whats been going on. Well... he proceeded to tell me that he believed everything that I told him and in the 38 years he has been at the clinic there have been a very small percentage of people, he said approximately 1 out of 1000 that have simalar stories. He validated many theories that we have concluded here in forums on our level. He told me that I am one of the 1 in 1000 people whos neurological system has been adversely affect from my very first dose of benzodiazepine use and that it could take quite some time to recover from this but he was very hopeful that it will fully recover. He also stated that in some cases it could be a very long time but there is just no way to know for sure. He also stated that for now as long as things do not get any worse on a pain level, ABSOLUTELY NO MORE DRUGS OF ANY KIND PERIOD. My whole neurological system needs nothing but time and only time. Thats not to say that anyone on any other drugs should'nt be. This is specific to me and not you. It was a day of many emotions for me, anger,fear and validation. This is a first I have heard of anyone on a professional level breaking it down like this. I was pretty floored to say the least. He said he wants to PERSONALLY see me every six weeks until things get better and to try and live as normal a life as possible in the mean time even if it hurts bad and at times seems impossible. I can say alot more but those are the key points on a brutally sobering day. As he was leaving, he apologized that there was'nt much more he could do for me and said that he would greatly appreciate if I would take the time to write a detailed account of my whole story and send it to him. He has been studying cases just like ours and is doing some kind of report paper on the subject. I will pick his brain more on that next visit. All in all.... WOW! What a day it has been. It was really bizarre to hear what I did today on a professional level. I will keep you guys up on how things develop on this story.

    April 23

    Symptoms as of late remain to be nothing short of punishing with no REAL breaks to speak of. I can still feel every muscle and organ in my torso pulling and aching all day, On saturday I had some muscle rigidity that would have made a healthy person fear for there well being. yesterday I had 2 nasty asthma like attacks and I dont have asthma. I.m tired of all this repritory stuff already. I'm still having isolated sleep issues. Apnea like, paralasis/breathing stuff. And lastly my insides sometimes feel as if they were rubbed raw with sand paper and bleach poured all over them. You get the point. My spirits are still good but I'm getting beat down endure this hell. I just wish it would stop and theres not even a slight chance of working in this state of being.

    April 28

    3 MONTHS OFF TODAY AND

    I have'nt posted for a week or so because, as I said before I hate to come on here and complain all the time. The last week has been alot of the same for me and its only getting worse. For 2 weeks now I have had pain in my left upper back that has been consistent and very painful at times right next to my spine. My breathing has been awful for the last week with asthma like episodes and extreme shortness of breath in which I find myself gasping for a breath every 4-5 minutes. I'm really tired of that one... My reflux is off the chart and nothing is helping. I wonder if it is causing the breathing issues. The last three nites my sleep has been interupted again with waking up to horrible feelings of weakness/ill poisoned feelings that leave me lay there for an hour or more like I will expire. I washed my truck on saturday and felt like I swam from florida to mexico in a hurricaine. I dont have much physical stanima left at all. Anxiety is a given for anyone getting a beating on this level and only complicates matters more. I still have absolutely no appetite and dropped a pound or 2 this week. Alot of my sporatic mental symptoms have eased up and my mind is very clear now but I'm absolutely sick and tired of being stared it in shock from people that know and care about me because of my physical state of being. Theres more I could say but I will stop here. All I know right now is that I have tapered myself right out of my job, my home, my health and my life. I was'nt broken 3 months ago and especially 6 or 10 months ago. I don't know what the answer is but this must stop before I become completely dysfuntional. I so so regret coming off now because I will repeat, I was funtcioning in the world adequetly. All I ask at this point is for the deterioration of the situation to atleast just stop. I hope 6 months will be a better update then this one.

    May 3

    Well the CT scan shows nothing at all... I guess thats a good thing but it means I just have to deal with this uric acid stones/crystals thing goin on. Also my breathing is as bad as it has ever been and its really got my attention now. And the muscle rigidity is way out of hand. It dictates what I do and don't do in a day and I will never get used to that.

    I hope I'm not getting some kind of asthma or something. If any of you had bad breathing symptoms please feel free to share it here. I'm really starting to worry because it has gotten consistantly worse in the last 2 weeks. The chiropractor I saw did meridian therapy and the energy flow through one of my grids showed that my lungs were way out of sync and 5 of the 12 were not flowing properly. He did lazer therapy after the eval and it has'nt done a thing so far. I go again tomorrow. He wants a MRI just to make sure but my DR said no again.

    Well I think you guys get the picture...

    For all the new faces here and theres quite a few, I pretty much did an Ashton protocol taper and am getting my ass kicked for three months. Thats not to say I'm bashing it but PLEEASE TAKE IT SLOW.

    Promise the next post will be much shorter.

    I could say a whole lot more but I just wanted to make my point and I wish that all you people that insist on using this drug DAILY< make the recipients aware of the danger and suffering that they are in store for sooner or later once they hit tolerance. By that time they wont even know who the old mary or billy is anymore...

    Karl H Ternay

    Feel free to email me if you have any further intrest in this matter.

    I dont expect to here from you though. i hope you have a conscience every time you inject this garbage into someone that you are risking SERIOUS PAIN AND DAMAGE to an innocent and unknowing victems life.

    Remember, you dont have to live the suffering... WE DO!

    Valium is an addictive drug, and getting off of it ... is tougher than heroine.

    All the family of benzodiazepines are addictive.

    To do a *quick taper* in the hospital, they administer anti-convulsant drugs ... because EVEN THOUGH the docs are in denial, they do know that some people DIE coming off these drugs, or start showing signs of mental instability ... to which the doc then prescribes anti-psychotics ...

    These drugs take time to come off of ... since a persons Central Nervous System needs to repair itself slowly.

    There is also the phenomena of *inter dose withdrawal* while still actively taking the drug ... which means that; as you are addicted to the drug, and even while taking the drug ... you begin to have withdrawal - in between doses.

    Also, a person will develop *tolerance* to the drug - which means their brain has adjusted to the dose - and to get the same effect as before, needs to have an ever increasing dose. This is called addiction when it pertains to *illegal* drugs.

    It is called *Iatrogenic Addiction* when it pertains to *legal* drugs ... administered by a doc.

    But, ADDICTION is still ADDICTION no mater where you buy your drugs from ... the neighborhood drug store, or
    the *pusher* just around the corner!

    Injecting this drug, seems to me to be particularly heinous ... especially if it works at first ...

    The patient in chronic pain will WANT to have the drug prescribed, but in the long haul, it will stop working ... and the pain will return ... because the brain is constantly trying to *right* itself, after an addiction and reset itself to its normal functioning mode. The patient in chronic pain, will soon discover that this drug does not actually WORK for pain relief ... but - instead - causes horrific degrees of pain and psychological symptoms.

    This CANNOT be *good* medicine.

    Seems like some people didn't get the point of those studies. They indicated that certain subtypes of gaba receptors do not get downregulated during prolonged use. Meaning: no withdrawal effects, and continuous effect without the need to increase dosage for future drugs just targeting those receptors.