Mitogen-activated protein kinase (MAPK) pathway is one of the most important cell signaling pathways in human brain. Many crucial cellular activities are controlled by the MAPK pathway including cell proliferation, differentiation, and apoptosis. Therefore, it is normally tightly regulated. In the paper we read for this week, the researchers discussed the pathological roles of different kinds of MAPK pathways (ERK, JNK and p38) play in human diseases, including the Alzheimer’s, Parkinson’s, and Amyotrophic lateral sclerosis (ALS). And hopefully by researching into these neurodegenerative diseases, we will be able to eventually find out treatments in order to provide these patients a better quality of life. While oxidative stress is commonly thought to be related to cell death that is associated with both Alzheimer’s and Parkinson’s disease, the risk factors for mutations that are linked to ALS still remain unclear and further investigations are required.
In Alzheimer’s, the reactive oxygen species such as hydroxyl radical, superoxide anion, and hydrogen peroxide cause the oxidative stress and trigger the JNK and p38 signaling pathways. And the activations of these two pathways often lead to cell apoptosis and the formations of senile plaques and neurofibrillary tangles which are generally found in the brains of Alzheimer’s patients and believed to contribute to the disease itself. Although there are no treatments found for Alzheimer’s so far, the researchers are looking into inhibiting the MAPK pathways mentioned above in order to slow the progression of the disease.
Like Alzheimer’s, Parkinson’s disease is another prevalent neurodegenerative disease related to oxidative stress. It is characterized by the accumulation of the Lewy bodies in the brain causing an increasing loss of dopaminergic neurons, and promoting inflammations by activating p38, ERK and JNK pathways. Mutations in multiple genes have been associated with Parkinson’s disease. Although various studies suggest that MAPK pathways contribute to the neuroinflammatory responses and cell apoptosis in Parkinson’s disease, due to its complexity of the pathway, it is very difficult to be diagnosed and cured. An alternative treatment that has been performed on the Parkinson’s patients is called the deep brain stimulation, although it does not cure the disease, it could effectively help the patients manage some of its symptoms.
Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease is caused by the mutation of the gene which encodes for SOD 1 (Cu/Zn superoxide dismutase) which ultimately results in the death of motor neurons. Although it is unclear how mutations of the SOD 1 gene results in ALS, the researchers believe that the activation of p38 MAPK pathway in motor neurons is important for ALS progression.
Many researches have been done on the neurodegenerative diseases introduced above in order to not only understand but also treat them. Although tons of money and efforts have been put into the studies of the MAPK pathways, due to their complexity, we still have a lot to learn about them. I am certain that life must be very difficult for patients with any of the diseases mentioned in this article, and no one will be able to understand exactly how difficult it is until one gets the disease. Therefore, I believe no matter how difficult to single out one pathway and how complex each pathway is, we should put in more and more resources into researches of these diseases. And eventually, we will be able to cure these patients.
Research that Gives You the Shakes! Or Cures Them!
If you could prevent Alzheimer’s, Parkinson’s, or Lou Gehrig’s disease, would you?
More than likely; with the current research carried out in control of the MAPK (mitogen-activated protein kinases) neurochemical pathway in your brain, these and other diseases can be examined and eventually treated directly. These diseases are all linked through different pathways that the same MAPK works in your brain. It is important to note that when it comes to the brain, the inner workings are very complicated, interconnected, and overlap with one another even with the same chemicals like MAPK.
The belief in Alzheimer’s disease in relation to MAPK is that brain cells are being told to die off faster than in a healthy adult. Oxidative stress tells the brain to have its cells self-destruct. From stress in the brain, a cascade of activities occurs involving MAPK, ultimately leading down to cells telling them to self-destruct. Loss of brain cells from this pathway has contributed to Alzheimer’s disease significantly with the obvious loss of areas of the brain in memory. Current research has been looking into blockage of the MAPK pathway that is telling these cells to die off, and lead to Alzheimer’s.
Parkinson’s disease is another detrimental one that is due to loss of control in motor function in the brain. MAPK pathways lead to inflammation of the brain and its cells that lead to death of the brain cells. In Parkinson’s patients, areas of the brain that regulate motor control are experiencing cell death from inflammation. The precise pathway for control is not yet known, but has been researched extensively, especially through the Michael J. Fox Foundation for Parkinson’s disease Research. Understanding of this pathway will help in understanding of how to regulate it and stop the progression of Parkinson’s and even help in early detection of its early symptoms.
Lastly, Lou Gehrig’s disease (amyotrophic lateral sclerosis) is due to mutated genes that lend ultimately to cell death. The areas affected are mainly motor control areas as well. The start is due to mutated genes that start signaling the MAPK pathways that will give rise to motor neuron death. The outcome becomes muscle loss, paralysis, and eventually death. Prevention of Lou Gehrig’s disease could be best understood through drugs that could stop different particular steps in the MAPK pathways.
These diseases are very detrimental to those that they affect, and that they may all be linked through very closely related paths is of extreme significance. Research on any of these diseases may affect each other; advances in one area can be important or influence treatment methods in another area. With further research, we can start to see what drugs will halt cell self-destruction and inflammation that lead to these diseases, and which ones will have the fewest complicating side effects in the brain. As with most treatments, one area that is fixed can lead to complications in other areas. The more we can understand MAPK and how it works in the complicated thing we call the brain, the more we can prevent and treat these diseases.
Photo courtesy of: http://feww.wordpress.com/tag/pesticides/
Vicodin, Morphine, Heroine, Oh My!
In society today, doctors give out pain medication in the class of opioids like they are candy. For things from a tooth ache to surgery, the range of ailments which one can be prescribed opioids for is rather large. Opioids include codeine, hydrocodone (vicodin), oxycodone, and morphine. You may be thinking: why is this a problem? Isn’t it a good thing that doctors are helping people manage pain? That answer is rather complicated…
First, opioids can be highly addictive. The addictive factors of opioids means that it is supposed to be regulated and there are steps doctors are supposed to take when prescribing as well as follow-up steps after prescribing. But speaking from experience, it is not very hard to be prescribed these drugs. Doctors giving out addictive drugs to people who are likely not in the need of them can cause many societal problems such as prescription pills being sold on the street.
Second, while the drugs I listed above are the opioids regulated medicinally, heroine is also classified as an opioid. Part of the problem with these drugs is people do not understand what they actually do. Opioids work so well in managing pain because they block pain receptors in the spinal cord. This means that pain signaling cannot reach the brain to alert it of the pain. The difference in the drugs from codeine to heroine is the amount of the signal being blocked.
Most people would not try heroine because of its addictive and harmful effects on the body. But then the question becomes if you wouldn’t take one form of opioid, why would you take any?
Messing with signal pathways to the brain can have many adverse side effects. Are doctors doing their due dillagence in perscribing such serious drugs for something that a simple over the counter pain medication might help with? So next time you have the option of taking even the smallest dose of an opioid, even if it is prescribed by a doctor, ask yourself, are you really in enough pain to jeopardize the risks associated with opioids?
Opioids, a Pain Killer? Or Cause of Pain?
Pain — A spasm in your back, a toothache, recovering from a fracture or dislocation, a degree of discomfort following surgery; it comes in many forms, but usually gets treated with some form of pain pill from Tylenol to hydrocodone (Vicodin).
The reason many of the drugs that help relieve pain are effective is because of their ability to target the process of pain signaling in the body. However, a specific group of these painkillers, known as opioids, have a serious risk of dependence and addiction and are frequently abused.
Why is this?
Opioids, many people may be familiar with their common names; they include but are not limited to: Morphine, codeine, hydrocodone, and oxycodone. These opioids are commonly prescribed by physicians for treatment of either chronic pain, or a post surgery treatment to take the edge off. While they may have varying side effects for different people who use them, opioids are very effective in targeting and almost completely numbing the human body’s ability pain signaling pathway. That would help explain why after their wisdom teeth get pulled most people are clamoring for some Vicodin.
Opioids do their job of stopping pain in several different ways, but one that really sticks out is the ability to slow, and even stop the process known as nociception. This process is responsible for taking in signals from nerves in the body and transferring them to the brain to be “felt” as pain. When these signals are on their way to the brain, nociception is responsible for the release of many neurotransmitters, and Substance P. When someone thinks about Substance P, they should just think of P for pain, because its role in the body is to make the body’s sensitivity to the pain signal being transferred very strong. So, after its release the neurons really start to fire and the signal gets shot up into the brain with some fervor. It is important for opioids to inhibit the release of Substance P. However, is it a good thing to stop the body from feeling pain?
Why not?
It was brought up in a class discussion, but why can’t we simply take opioids and not have to feel pain? There is one huge drawback to opioids, they are have a high rate of addiction and physical dependence. Something that is able to affect the brain in such a drastic manner can cause many harmful problems if abused. Maybe people who have been affected by a heroin addiction will attest to that. Heroin is also known as morphine diacetate, is a synthetically produced opioid that is highly addictive and known for incredible negative withdrawal symptoms, including insomnia, vomiting, and involuntary spasms of the body. Also to note, these symptoms can begin to show a presence as early as six hours after taking the drug.
Heroin is just another opioid, which before it became widely abused was just another attempt at altering morphine to make it more effective. The stories of addiction to heroin are very similar to most who abuse any opioid; almost impossible to overcome without treatment, because of the severe emotional and physical distress caused to the body.
So it is important to answer the question do opioids cause more pain than they relieve?
Can we control our addictions to pain medications?
Throughout late medical history we have seen extensive abuse of pain medications as they are highly addictive to those who are prescribed them. These highly effective medications for pain are also called opioids. An opioid is a type of psychoactive chemical working by binding to its complimentary opioid receptors. These are primarily found in the central nervous system (CNS) and peripheral nervous system (PNS) but also in the gastrointestinal tract. The receptors in these organ systems mediate both the beneficial effects and the side effects of opioids. These drugs are among the world’s oldest as we see the earliest form of them used more than 5,000 years ago.
The reason these drugs work so well is that they have a great reduction in the brain for perception of pain. We still are receiving the stimulation of the pain but our brain is unable to know that this stimulation is indeed pain. Patients experiencing great amounts of pain are often prescribed morphine, one of the more popular opioids. Doctors will also prescribe opioids such as morphine to patients that are near death so they may pass with little amounts of pain as these drugs raise the pain tolerance. For those not on their death bed these pain medications have many side effects and problems with addiction. According to a 2005 national survey on drug use there were almost 2 million Americans dependent on opioids and even more, 4.7 million, use opioids for nonmedical purposes. Obviously there are problems with the system for prescription as we see these numbers rising into our current situation. “The increase in the legitimate use of opioids has been paralleled by a rise in abuse of these drugs, with a 63% increase in opioid deaths during the 5-year period from 1999 to 2004” (Institute of Addiction Medicine).
How do we control these addictions? Traditionally, researchers have looked at controlling the dopaminergic system for addiction to drugs such as opioids but new paths have been trodden for controlling addiction through the glutamatergic system instead. Glutamate is similar to dopamine in that it is a primary excitatory neuron in the brain involved with the side effects, withdrawal, and reward that opioids are linked with. What researchers hope to do is use antagonists (drug that blocks the binding of the natural neurotransmitter) to stop withdrawal and therefore hope to stop the need to go back to the drug. The goal would be to remove the symptoms associated with withdrawal so that patients or addicts were unable to develop a true bodily addiction to the drug in the sense that their body will not need the drug to function properly.
Would this work? Theoretically, it would. We could prescribe pain medications more freely and not worry about addiction and abuse of opioids. Obviously there are many cons to this extra prescribing. Opioids have many unpleasant side effects but these would often be more desirable than pain. This leads to another problem: If we remove the biological addictive factors will we not have a psychological dependence? A patient will quickly associate the pain medications with relief of pain just as reward association often occurs in psychology. This dependence would be also difficult to overcome as there is not necessarily a way to treat this with pills as we could a biological dependence. There are a few ways that we can attack this problem with the better option being a punishment system. As pharmaceutical companies have done in the past we can introduce additives to the drugs to induce more side effects that would me unpleasant enough to deter the prescribed patient to return to the drug for smaller amounts of pain or even taking Tylenol/Advil for larger amounts of pain. This obviously has some ethical problems associated but we must open discussion for what needs to happen next.
As we get closer to solving the problem of biological dependence through manipulation of the dopaminergic system and, more recently, the glutamatergic system we run into other problems with psychological dependence. Much more research needs to be done to successfully do away with biological dependence as this is the first step into conquering the addictive properties of opioids but soon we need to tackle new problems such as our mind’s control over our habits concerning addiction.
Codeine Candy for Halloween!
Common prescription painkillers are being handed out like free smoothie coupons from doctors. Does your back hurt? Get some codeine. Pain in your left foot? There’s some vicodin for that. Twisted your neck the wrong way looking at the new coworker? I’m sure your doctor would be more than able to get some morphine for that. 
The growing concern with these, and other, types of opioids is their naturally addictive tendencies, especially in those patients who have histories of drug abuse. At the same time, doctors are increasingly prescribing these very powerful medications in excessively high and large amounts. Additionally, the question of how much pain medication is necessary to lead a normal life comes about; is it really acceptable for every person to take such dangerously strong drugs that could cause serious long-term side effects just because they slept the wrong way? As always, further research will be carried out in the upcoming years, and the results will be most insightful.
The clear problem with over prescribing doctors is that a patient given 40 pills of vicodin will more than likely not need to use the full amount prescribed because the root pain will have dissipated before then. As a result, these patients end up with leftover pills that they may end up using at later times when they have minor aches when the situation is not appropriate or severe enough, or selling them on the black market illegally to those seeking the psychoactive effects. Neither of these is ethically sound options, but then it seems fair to question those prescribing such vast amounts of medication. Are doctors giving out too much medication just because they feel pressured to? It has been shown that patients leave much more satisfied from a doctor’s visit if they leave with a prescription, than if they’re told to rest.
Additionally, busy schedules pressure doctors to have as few repeat patients with repeat ailments as possible. Giving too much of a medication seems like an easy way to quick fix these patients and to prevent them from coming in again for the same problems. Unfortunately, these moments of over prescribing opioids leads to addiction and reduced sensitivity to them, not to mention all the physical side effects of diarrhea, nausea, etc. While trying to prevent patients from coming in with back pain over and over again, a doctor may feel it necessary to over prescribe, leading a patient down the road to addiction which would have even more problematic effects than just the original back pain itself. Is over prescribing really the best option? Like most things, there are situations where it is more appropriate than others.
In order to avoid these severe addictive properties, avoidance of the medication itself seems a good idea. Are Americans becoming “wussies” about every little pain that crosses their way? The quick-fix drug for every ailment is the ultimate goal, but is it not necessary to have a certain amount of sensation for pain? Personally, in order to prevent abuse of these opioids, I feel many times that doctors should be bold enough to honestly tell their patients to “toughen up” and fight through certain types of pain, because they will subside quickly enough. In chronic pain cases, other methods would be appropriate, but to someone looking to get that quick fix medication, they must ask themselves if they’d really rather suffer through a fair amount of back pain, or become addicted to Percocet for the remainder of their lives, not being able to live or thrive without a drug to take them to normalcy.
Source:
http://blackgirlsguidetoweightloss.com/its-all-mental/on-enabling-myself-hiding-junk-food-around-the-house/
Overprescription of Opioids Leads to Dependence
Opioids usage has become as common as taking daily vitamins. An opioid is a psychoactive chemical which diminishes the sensation of pain. The common name for opioids are painkillers. Whether over-the-counter or not painkillers are one of the most 
easily obtained drugs on the market. Today’s society relishes the abundance of these painkillers and continues to use them at an astonishing rate. Now having tolerance to pain would not be such a bad thing if it were not for the addicting nature of painkillers. For people suffering chronic pain over-the-counter painkillers such as morphine, vicodin and oxycontin are typically prescribed. However, strong painkillers such as these possess a high risk for the taker to become addicted to and dependent on the drugs.Famous celebrates such as Michael Jackson and Heath Ledger both fell victim to overdose caused by their dependence on opioids.
How can innocently taking a strong painkiller such as vicodin after a surgery turn into a dependence and in an extreme case, death? The answer lies in the chemistry of the brain. The pathway of pain begins in the peripheral nervous system with let’s say a cut on your finger. The signal travels from the receptors in the finger through the body to the spinal cord. The spinal cord then relays that signal to the brain where the signal is processed as pain. Speaking more in depth about the role of painkillers in the pain pathway, painkillers reduce the expression of a chemical called substance P. Substance P expresses itself at an exponential rate. Meaning that if one substance P is initially produced as the neuron fires that one substance P becomes two, which then 
becomes four, eight, sixteen and so on. Painkillers target the expression of substance P and reduces its production. However, inside the brain, as the neurons receive the opioid, a genetic transcription factor, CREB (cAMP response element-binding proteins), begins to code your genes to that painkiller. This means that the body becomes less receptive to the painkiller. Tolerance builds up and more dosage of the painkiller is required to obtain the same satisfaction as when the usage began. Along with the accumulation of tolerance, a person can develop an addiction to the pleasurable effects of the drugs. Addiction does not lie with the same genetic transcription factor as tolerance, instead a new genetic transcription factor, delta FosB, codes DNA for the craving of the painkiller. Death from overdose comes from the painkiller shutting down the sensitivity of the nervous system. Instead of turning off the body’s pain reception, overdose causes all reception in the brain and spinal cord to halt.
If the risks of addiction and overdose exist, why then are painkillers prescribed so often by doctors? One of the main reasons that doctors prescribe painkillers regularly is because they do not wish to lose their patients. If a doctor does not provide a patient with what they want, then there is a chance that the patient will leave to find a doctor who will give them what they desire. Therefore, doctors are almost forced into prescribing painkillers in order to keep their patients. Does fault solely lie with timid doctors afraid of losing patients? Society too plays a role in the overprescription of painkillers. Due to the abundance of pain medication people now-a-days are more likely to grab a bottle for the slightest pain. Pain tolerance is a factor to this. For example, I see myself as having a high pain tolerance and so rarely do I take pain medication. Because of this a small dosage usually does the job for me. If you look at my mother on the other hand, she has a very low pain tolerance. She not only takes pain medication more often but also needs more dosage to relieve that pain because she takes painkillers more often. Therefore, the fault of overly prescribed pain medications lies both with eager to please doctors and people with varying levels of pain tolerance. To place restrictions on the prescription of opioids would be a difficult manner as there is no universal chart for pain. Everyone experiences pain differently and as such there can be no definite way to administer the prescription of painkillers which is completely inclusive.
Hope for suppressing the addictive effects of prescription opioids?
When someone hears the word Vicadin or morphine they might often think about the negative effects of these drugs as they are extremely addictive and are also used recreationally for their psychotropic effects. A great number of people have been prescribed an opioid painkiller such as Vicadin, Codeine, or Oxycodone for various different reasons such as a post-surgery drug to ease the pain. Due to this fact, it is very important that our society knows just what is at risk when using these powerful painkillers. These painkillers are used enough in our society today that it’s not new to hear about opioids being very addicting and patients developing both a dependence and tolerance to the drug. Many people might ask, if it is known that using opioids can cause negative side effects such as dependence and tolerance, why are they still prescribed so frequently?
Opioids are such effective painkillers for many reasons. One main reason is that they have no analgesic pain ceiling, meaning they can block all pain. This is extremely important with serious surgeries that come with extreme pain during recovery. They are also used so frequently because they don’t have any negative effects on your liver, unlike the commonly used pain relievers like Advil.
Previous studies conducted in attempts to identify why opioids are so addictive have been focused on the dopamine system. This is mainly due to the fact that most addictive drugs increase the submission of dopamine, leading scientists to believe that the dopamine system would be involved in opioid addiction as well. However, in recent studies, scientists have been diving into the glutamate system as there has been recent evidence in the past five years that glutamate plays a roll in opioid addiction. Throughout the paper, “The role of glutamate and its receptors in mesocorticolimbic dopaminergic region in opioid addiction” many experiments are outlined that suggest glutamate is in fact an important piece to the puzzle describing opioid addiction.
Glutamate is the most abundant excitatory neurotransmitter in the brain. Glutamate binds to its glutamate receptors, ultimately opening a channel allowing ions to flow through and trigger an excitatory current. How is this abundance of glutamate and its respective receptors related to the development of an addiction to opioids?
After reading and analyzing the topic paper in class, it became very clear as to how glutamate is related to drug addiction. The paper did a great job laying out all of the specific pieces of evidence and just what they did to prove this relationship. One of the main studies that our paper focused on was the use of glutamate receptor antagonists, which essentially block the receptors from doing their job in excitation. There were many specific instances where scientists tested the effects of these glutamate receptor antagonists on addiction to opioids and they found that use of these antagonists successfully regulates drug tolerance and dependence.
These findings are very exciting as it would be ideal to be able to control the addiction of opioids, since they are extremely effective and prescribed so frequently. Although its seems as if scientists are on the right track as they explore glutamate receptor antagonists and their aid in preventing addiction, further research is needed due to the fact that glutamate receptors affect many different processes in the body and blocking them could cause effects other than suppressing addiction.
The Role of Glutamate in Opioid Addiction
This week in class we learned about opioid addiction and the role that glutamate plays in it. Opioids enjoy widespread use as pain relievers, some well known opioids are codeine and morphine. They are specifically used in order to treat acute pain, or in order to treat chronic, disabling pain that is associated with terminal diseases. Recently however, opioids are being used to treat non-malignant chronic pain, that is pain that is not associated with an illness or injury. This has lead to a growing number of people becoming addicted to opioids. For this reason it is very important that we understand what causes opioid addiction and how to prevent it.
The article that we have read for this week tells us that the brain pathway that is most responsible for addiction is the mesocorticolimbic dopaminergic pathway. The pathway is composed of the ventral tegmental area(VTA), the nucleus accumbens(NAc), the amygdala(AMY), and the medial prefrontal cortex(mPFC). These regions of the brain are responsible for the reward system of the brain, meaning that it reinforces certain actions once they are performed.
Now we can talk about how glutamate and its receptors play a role in opioid addiction. In the article it was said that the NMDA ionotropic receptor is very important in the development of addiction to opioids, as there are more NMDA receptors in the brains of morphine addicted rats. It was also shown in this paper that the substance MK801, which blocks the NMDA receptor upon binding with the receptor, can block the pain tolerance and physical dependence which opioid use can lead to, as well as the drug seeking behavior which drug addicted individuals display. It is also revealed in this paper that there are a number of specific metabotropic receptors which are linked to withdrawal symptoms in opioid addicts.
The article also investigates the signal transduction pathways which are responsible for opioid addiction. The release of calcium ions upon activation of the NMDA receptor leads to many different effects on the cell which all create withdrawal symptoms if the NMDA receptor is overstimulated. Another important pathway to consider is that of protein kinase C which upon the increase in the calcium concentration in the cell, the kinase promotes the creation of copies of itself and phosphorylates, that is attaches a phosphate to a G-protein which leads to desensitization when the G-protein in question is on an opioid receptor. Another important pathway to consider is the CREB pathway which is a common factor in many other cases of physical and psychological dependence. The application of opioids increases the concentration of CREB and related proteins and causes the copying of new proteins and leads to addiction. Lastly, the MAP kinase pathway which is important in rewarding response and behavioral sensitization which is brought on by the administration of psychostimulants.
The interaction of glutamate with other neurotransmitters was also explored in this article. It is said in the article that there is an interaction between opioid receptors and glutamate receptors which is vital to opioid dependence. It is also shown that there is a connection between glutamate and dopamine as it is shown that glutamate increases the amount of dopamine in NAc and increases the activity of dopaminergic neurons. It is also shown that activation of opioid receptors in the brain inhibited the activity of GABA neurons and inhibited the chemicals release. GABA normally inhibits dopamine, so the result of the opioid application is the increase of dopamine in the system. The article also briefly mentions substance P which the researchers writing this paper say that it has a relationship with glutamate, but that its role in opioid dependence still has to be studied.
In our small groups this week we primarily discussed changes in medical procedure, as in if we could ameliorate the concerns about addiction in the prescription of opioids. One very interesting thing we talked about was whether it would be better to just sever the nerve bringing pain sensation to the brain rather than worry about medication and the discussion gradually shifted to not over whether the severing of the nerve would be the practical thing to do, but what the implications would be if we gave this procedure to people. We talked about how pain is a valuable teacher, telling us about whether an object is dangerous or not, or whether we have been hurt or are hurting ourselves.
Morphine, Vicodin, and Oxycodeine: Why are opioids used when they are so addictive?
You may be familiar with several of the popular opioid medications (morphine, vicodin, and oxycodone) prescribed to people with severe pain. Also, you may have heard about the serious addictive effects which may result from taking these drugs. However, two questions that seem to never be asked are: 1) why are these drugs so addictive? and 2)if they are so addictive why to doctors continue prescribing these opioid medications?. As part of this week’s discussion, we attempted to analyze the addictive nature of opioid drugs and understand why we continue to use such drugs even though they are highly addictive.
The article we looked at focused on a molecule called glutamate, which is found in most part brain, and its involvement in the opioid addiction mystery. It turns out glutamate may play a bigger role in addiction than previously thought. Since glutamate is one of the most abundant neurotransmitters in the brain, it is found in many different areas including the ventral tegmental area and nucleus accumbens which are believed to play a prominent role in addiction. When opioids are used, more glutamate neurotransmitters are released and interact through many complex pathways causing an increase in dopamine, which is the neurotransmitter associated with the reward. This causes the body to think it is being rewarded for taking opioids. Additionally, when glutamate binds with its own receptors it can cause addiction and withdrawal-like feelings by acting through many different biological pathways. However, I would like to note addiction is much more complicated than this and more research is needed to understand addiction better.1
This leads us to the question why do we use opioid medications if they are so addictive? As discussed in class the key reason seems to be the effectiveness of stopping pain. Besides opioid drugs, the other common type of pain killers are non-steroidal anti-inflammatory drugs (NSAIDS) which includes Advil and Aleve; acetaminophens likes Tylenol; and aspirin. All three pain killers act by stopping an enzyme (called cyclooxygenase or COX) found throughout the body which is responsible for feeling inflammation and pain. NSAIDS and aspirin block this enzyme in the areas outside the brain while acetaminophens block the enzyme in the brain. Although these drugs are successful, they come with side-effects such as liver and kidney damage and blood thinning after extended periods of time. 2 However, opioid medications act in a different way therefore making them excellent pain relievers. Opioids change the perception of pain by working on the spinal cord and the brain. Opioids pain killing characteristic works by closing and opening a variety of channels in the brain resulting in a reduction of the brains ability to feel pain. Closing and opening these particular channels are more effective at reducing pain than by stopping the COX enzyme either in the brain or the peripheries. Additionally, as a result of changing channels instead of stopping an enzyme, opioid usage do not have many of the long-term side-effects associated with the other pain killers. However, since they interact with channels in the brain addiction is much more prevalent than with the other drugs.3
Therefore to summarize, opioid medications such as morphine, vicodin, and oxycodone acts in such a way that when taken glutamate is released and through several pathways causes dopamine to be released. This results in a feeling of reward. Additionally, when excess glutamate binds to certain receptors in the brain one feels addictive and withdrawal-like feelings. However, the reason why opioids medications continue to be used is because they are more affective at reducing pain and contain fewer physical side-effects as compared to NSAIDS, acetaminophens, and aspirin.
Finally, this raises questions about what should be done with opioid medications. Would you rather live a life without pain but have the possibility of becoming addicted to your medication or would you rather live with pain but know you will not be overcome by the psychology effects of addiction? Or should scientists continue expensive research in the hopes of stopping the addictive nature of the opioid. There seems to be not right answer but it does appear opioid medications are going to remain in our society for the foreseeable future.
Sources:
1) http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000802/
2)http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004928/
3)http://www.webmd.com/pain-management/opioid-analgesics-for-chronic-pain