Say Goodbye to Chronic Pain: The Answer Could be Glutamate

Say Goodbye to Chronic Pain: The Answer Could be Glutamate

Angie Radek

What do McDonalds, Wendy’s, Taco Bell, and every other restaurant have in common? Glutamate. Glutamate is a very popular salt and chemical used in foods all around the world. Western countries, like the U.S, are best known for processed food that contain glutamate. But, other parts of the world struggle with inexpensive food that contains glutamate due to economic reasons. Because of this processed food and struggle with diet, the world suffers with nutrition, obesity, and most importantly, pain control particularly in chronic pain. Dr. Gebhart focuses on visceral pain, chronic prostatitis/chronic pelvic pain, and the symptoms associated with this type of pain. But, can the pain and symptoms be minimized or eliminated if we just promoted a healthy diet and eliminated glutamate, instead of jumping to pain killers and difficult surgeries?  

Dr. Gebhart argues that chronic prostatitis and chronic pelvic has symptoms such as the pain, burning, or the need to frequently urinate because it is visceral. This is important because Dr. Gebhart stresses that visceral, or the internal nervous system, is unique because it is an intrinsic system. Additionally, Dr. Gebhart focuses on this system because the pain is usually an inflammation, not felt at the source but somewhere else, has poor localization, and has hypersensitivity. This visceral pain is unique because it is extremely difficult to control, difficult to target the source of the pain, and which neurons are involved. Thus, a poorly understood system.

            But, one of the most unique characteristic of the visceral pain system that Dr. Gebhart emphasizes on is that the organs obtain innervation from two nerves. This is key to understanding any internal pain because one can have hypersensitive organs. This is reflected by a leftward shift in the stimulus response function. This is important because sensitization is a property of nociceptors, which is our pain nerve endings. Dr. Gebhart proposes an example that because of this, in irritable bowel syndrome, low volume urine will cause an uncomfortable feeling when normally it would not. This system is key in understanding the chronic pain felt in diseases such as chronic prostatitis and chronic pelvic pain.

            Additionally, Dr. Gebhart goes in great detail about the processes that chronic pain takes place. For example, in bladder, it goes from the bladder, to the PG, to the PN, and finally to the sacral/parts of the brain. Also, it is emphasized that the vagus nerve cell body in the nodose ganglion transmit the pain to the NTS and into the brainstem. Recent research has focused its attention into studying the specific nerve associated with chronic pain. For example, in a study by Miller and Fraser the researchers studied the importance of pelvic never fibers in endometriosis, another disease in women that can cause chronic pain (Miller et. al, 2015). This research is a great contribution and outlines the importance of the anatomy of the pain but is not a solution to chronic pain itself.

            Chronic pain is one of the most troublesome health problems due to its complexity, treatment methods, and pain control. But what if something as simple as eliminating or lessening glutamate consumption can eliminate chronic pain?

            Newer research suggests that glutamate consumption can impact the amount of chronic pain an individual has. A study performed in Kenya with the help of doctors from University of Michigan suggested that cutting “monosodium glutamate from[subject’s] diets, symptoms improved” (American University, 2018). Also, this study concluded that symptoms like chronic fatigue, cognitive dysfunction, headaches, migraines, and sleep issues are reduced when glutamate consumption is cut.

            Since chronic diseases and the visceral pain system is poorly understood, newer research suggest that chronic pain and its symptoms could be eliminated if individuals made diet modifications and attempted to reduce one chemical: glutamate. Instead of attempting to understand the exact neurons, pain fibers, and other association with pains, research should gear towards fully understanding how glutamate levels is affecting the body, brain, and visceral pain system because it is reducing symptoms of chronic diseases.

Although it is difficult to control one chemical, many individuals, the government, schools, doctors, etc. should take nutrition and diet modification seriously because it is affecting the U.S and other parts of the world in a negative way. Diet should be part of an individual’s prescription and not just prescription drugs or typical treatments. Sometimes, the simplest change can make the largest difference.

Sources

https://www.ncbi.nlm.nih.gov/pubmed/26314611

https://www.sciencedaily.com/releases/2018/02/180216142702.htm

Alzheimer's and Beta Amyloid: A Complicated Relationship

In the impressive piece by Dr. Roberto Fernandez titled Early Alzheimer’s disease blocks responses to accelerating self-movement and the subsequent presentation, Dr. Fernandez thoroughly explained the progressive pathology of Alzheimer’s disease (AD) as well as his desire to find pathological markers to outline its development within the human brain. He began by explaining that this neurodegenerative disease is most prevalent in the population above 65 years of age with dementia being the prominent hallmark of diagnosis.

In explaining the basis of AD, he presented some of the pathology behind the disease which is currently known. Dr. Fernandez, in his presentation, dictated how Beta Amyloid and Tau are both proteins that are responsible for maintaining microtubule structure and transport of materials via tubules but when these proteins become abnormal, they form plaque within the brains of AD patients. This plaque subsequently blocks transmission at synapses resulting in inhibition of brain activity. It was also noted that plaque formation often begins in the medial temporal lobes (memory center of the brain) and the progress towards the parietal and frontal lobes which is often why dementia is an early sign of Alzheimer’s.

What was most interesting, however, is his explanation of the visuospatial symptoms that are prevalent in over 1/3 of AD cases. He explains that visual processing of day to day life often involves the ventral region of the brain, which is responsible for face identification for example, and the dorsal region, which is used for attaching meaning to locations of objects. He stressed this fact as the information from these two regions are used to form different networks and when posterior cortical and parietal atrophy begins to appear, the degeneration of these networks occurs. In order to test this network degeneration, he ran a set of experiments in which he had subjects from a wide age range and with differing stages of AD perform simulated driving tests where one would have to remember how to get to and from certain locations after being given initial instruction. Dr. Fernandez observed the number of memory errors and accident that occurred within the simulator to test the subjects’ ability to create and retain a temporary visuospatial memory map. The way he quantified his test was by giving the example of how AD patients would often be suddenly unable to remember how to get to a store from their home and back, after having done so a multitude of times because of this degradation of neural networks. His goals for the experiment were to attempt to find markers of network degradation in AD by age and AD stage by correlating these descriptors to the number of errors in the simulator.

Still, Dr. Fernandez also explained that much is still not known about the pathogenesis of Alzheimer’s disease with many scientists still wondering how the dysfunction of the aforementioned proteins causes synapse degradation or why exactly the disease is more prevalent as age progresses, for example. However, scientists at the Stanford School of Medicine have presented work that claims Beta Amyloid dysfunction is not the sole reason for network degradation in the brain. While scientists are looking for pharmacologic methods to rid the brain of Beta Amyloid, Dr. Carla Shatz is looking for methods by which to protect synapses from being inhibited by the protein instead.

Dr. Shatz claims that AD “starts to manifest long before plaque formation” and has found that as Beta Amyloid begins to develop into plaque, it forms small clusters that are soluble and travel in the brain which eventually binds strongly to a receptor on neurons that begins a process where synapses with other nerve cells are eroded. In her experiment, she used strains that were highly susceptible to the impairments of AD and found that a receptor protein named PirB with high affinity for Beta Amyloid in the soluble form began the aforementioned erosion process. In continuing her research, Dr. Shatz utilized mice that lacked PirB and were highly susceptible to AD which led to her observing mice with high levels of Beta Amyloid protein but no neurodegenerative effects. The question of why this observation is occurring is still being found.

In the end, Dr. Fernandez may be able use the aforementioned research to finally find the markers for AD progression he was looking for. It is possible that while his subjects may have had a wide range of Beta Amyloid concentrations in their brain tissue, the reason behind their dementia and neurodegeneration may be the receptor proteins that bind the abnormal Beta Amyloid rather than simply the age of the patient.

Works Cited

1)     Fernandez, Roberto, and Charles J. Duffy. “Early Alzheimer's Disease Blocks Responses to Accelerating Self-Movement.” Neurobiology of Aging, vol. 33, no. 11, 2012, pp. 2551–2560., doi:10.1016/j.neurobiolaging.2011.12.031.

2)     Goldman, Bruce. “Scientists Reveal How Beta-Amyloid May Cause Alzheimer's.” Stanford University School of Medicine, 19 Sept. 2013, med.stanford.edu/news/all-news/2013/09/scientists-reveal-how-beta-amyloid-may-cause-alzheimers.html.

3)     Hamley, I. W. “The Amyloid Beta Peptide: A Chemist's Perspective. Role in Alzheimer's and Fibrillization.” Chemical Reviews, vol. 112, no. 10, 2012, pp. 5147–5192., doi:10.1021/cr3000994.

Jetlag Immunity: Messing with the Levels of Vassopressin Could alter the Body’s Master Clock and Cure Jet Lag

Earlier this semester, Dr. Dan Cavanaugh spoke to the class about circadian rhythm. Professor Cavanaugh began his presentation by providing background information regarding circadian rhythms. He explained that most physiological processes are under circadian control. He went on to state that there are two different types of circadian rhythms, rhythms that are driven by external cues and endogenously driven rhythms. Professor Cavanaugh then explained the Mammoth Cave Studies of 1963. These cave studies examined circadian rhythms driven by the external stimulus of light. It was also noted that there are a few properties that hold true for all circadian rhythms. All rhythms have a period of twenty-four hours and continue to function even in the absence of temporal environmental cues. Circadian rhythms can also be entertained by environmental cues. The body also has one master clock that regulates all other circadian clocks. This master clock is known as the Suprachiasmatic Nucleus (SCN). 

            Professor Cavanaugh then spent some time covering the molecular basis of circadian rhythms. He provided a figure that explained the transcriptional/translational feedback loop that is formed between CLOCK/BMAL and PERIOD/CTYPTOCHROME. A recent article found on National Geographic’s website examines jet lag and its possible basis stemming from the inner workings of our circadian clocks. This recent article suggests that vasopressin is the culprit responsible for the feelings of tiredness and disorientation associated with jet lag. Upon first glace, Vasopressin would seem like an unlikely culprit. It is usually associated with the regulation of bodily fluids. However, recent research has pointed to Vasopressin allowing certain cells of our brain’s master clock, the SCN, to communicate with one another.Hitoshi Okamura at Kyoto University in Japan was one of the co-authors of this study. The experimenters first wished to see if they could induce a state similar to jet lag in mice. To do this, experimenters used two separate groups of mice. One group contained all Vasopressin receptors intact. The other group of mice was lacking two hormones that were key Vasopressin receptors. Both groups were placed on a twelve-hour light and dark cycle for two weeks.

            The researcher then advanced the cycle for all mice by eight hours and recorded how long it took for both groups to become resituated. The mice with all Vasopressin hormones intact took almost four times the amount of days to readjust. To confirm these findings, researchers used drugs to block the vasopressin receptors in the intact mice and then repreated the above experiment. Now, these mice also recovered from the jet lag quickly. For this study, Okamura deduced that Vasopressin seems to hold a role in keeping the SCN on track. Okamura also goes on to say that this intact clock has been advantageous for our ancient ancestors. Not until the inventions of planes and jet lag has this become a problem. Okamura said there could be a correlation between their findings in mice to human clock function. Humans also have Vasopressin receptors cells in their SCN that could have similar functions. 

            Although these findings may seem promising, some scientists are worried that the decreased level of Vasopressin receptors may unintentionally have negative effects on other crucial bodily processes. A scientist who played no part in this study, Michael Gorman, is worried that the lack of Vasopressin receptors will hinder the maintenance of a healthy blood pressure and healthy fluid levels. A safer alternative may be to look for hormones that are either up or downstream of the Vasopressin receptors. These hormones could be altered to offer some relief from issues such as jet lag.

Article Referenced:

https://news.nationalgeographic.com/news/2013/10/131003-jet-lag-vasopressin-circadian-rhythm-clock-science/?_ga=2.137715826.316216850.1524440602-533510220.1524024932

Magnetic Memory

By Emma Sims

Effective treatments for major depressive disorder have been in high demand since medieval times. Antidepressant prescription drugs first became available in the twentieth century, yet still are not effective for many patients and often cause multiple side effects. Alternative treatments such as electroconvulsive therapy (ECT) have lesser-known detrimental features. Some patients may experience memory loss and confusion, as Brenda Griffith describes in the Scientific American article, "Fighting Depression with Magnets." Griffith has tried over twelve different antidepressant medications and ECT, all of which brought negative side effects and no relief for her depression. Finally, Griffith began transcranial magnetic stimulation (TMS) as a last line of treatment and saw drastic improvements in her depressive symptoms.

The process of TMS involves an electromagnetic coil placed against the head of a patient, usually at a location specific to their condition. Repetitive TMS provides stimulation through induced electrical current in axons. While the process provides electrical stimulation in cortical areas, deep brain structures such as the hippocampus are inaccessible through TMS. Regions demonstrating increased fMRI connectivity with specific deeper cortical structures are not always the same as the outer cortex areas stimulated, meaning that locations directly above the targeted area do not necessarily correlate with what lies directly underneath them.

TMS is not only useful for lessening symptoms of depression, but also beneficial for strengthening memory ability. Dr. Joel Voss, a neurology researcher at Northwestern University, focuses his work on memory improvement and recently held a lecture at Loyola University Chicago on the manipulation of memory ability through TMS. Voss's study compares success of a spatial memorization task with measures of precision of a simple memory task. In older adults with declining memory, he compares both item recognition and source recognition. His results show that source memory significantly improved (by as much as 30 percent) in participants who received TMS treatment, and the memory increase remained relatively better up to one week later after initial treatment in experimental group participants. Voss chose to electrically stimulate the hippocampal-cortical network in order to best reach the hippocampus, as it is a deep structure and not easily accessible through TMS.

Overall, transcranial magnetic stimulation is becoming more successful and common in treating various cognitive abnormalities such as depression and memory-related disorders. However, TMS must be used frequently over a substantial time period in order to prove successful in patients. The cost of many treatments can range from $300-$500 and adds up quickly in its typical thirty to forty sessions. Medical insurance has been recognizing and covering TMS costs much more frequently than before, and hopefully will continue to become more affordable for individuals in order to greatly stabilize and improve their daily lives.

Sources:
- Joel Voss lecture
- Picture: https://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation
- https://blogs.scientificamerican.com/observations/fighting-depression-with-magnets/

Enhancing Memory Consolidation

Dr. Ken Paller recently did a talk in regards to targeted memory reactivation (TMR) and sleep. Each of us spend about a third of our lives asleep. In the time we are awake, we are constantly learning new things and consolidating that information. In his study, Dr. Paller set out to see if TMR could actually improve learning by selectively encouraging memory reactivation during sleep. Sleeping naturally aids learning and every day we learn things that are important, and others that are not. What makes learning effective is repetition which we can do while awake, but it also occurs while we are sleeping. Dr. Paller discovered that subtle sounds played while sleeping can strengthen memories. Study subjects would learn a memory task that included an auditory component and would then sleep with electroencephalographic monitoring. The sounds were presented during sleep and when the subjects woke up, their memory was tested. General memory consolidation is a normal part of sleeping. However, with TMR, the consolidation mechanisms can be improved and specific memories can be reactivated during sleep to strengthen them. Paller also found TMR to provide an advantage for learning a specific skill, enhancing good habits, and improvement in a therapeutic setting.

The article “How the brain consolidates memory during deep sleep” by Iqbal Pittalwala of Science Daily also talks about the consolidation of memory during sleep. It opens up by stating that even though our bodies are not very active during sleep, our brain is. There are high frequency brain waves from the hippocampus and large amplitude, slower waves in the cortex. The memories we make throughout are day are initially stored in the hippocampus, and some are then progressively transferred to the cortex as long-term memory during sleep. Researchers from UC Riverside developed a computational model which demonstrated that synaptic changes affect the patterns of slow oscillations. This promotes a kind of reinforcement of specific firing sequences of the cortical neurons which represents a replay of specific memory. This can lead to increased learning and consolidation of memories in the brain. Their research found a mechanistic explanation for how memories are formed in the cortex and become independent of the hippocampus. By influencing these oscillations, the hippocampal input activates selective memories during sleep and causes a repetition or rehearsal of these memories. This relates back to Dr. Paller’s research since he used TMR to actually strengthen this effect and to target specific memories. The article states that when memories are rehearsed in the brain, the corresponding synapses are strengthened. Dr. Paller discussed the plasticity of the brain. The more you use a part of your brain, the stronger the synaptic network will become.

The research study along with this article demonstrate just how important sleep is for learning. There is an average of 4-5 alternating cycles of NREM and REM in an eight-hour sleep period. Therefore, it is important to get enough sleep so that we can effectively learn and form new memories. We now know it is even possible to improve recollection through the methods used by Dr. Paller involving TMR.

References:

https://www.sciencedaily.com/releases/2016/04/160414214830.htm