Cobbers on the Brain

By Hannah P.

How do we feel pain? 

When we feel pain sensory receptors in our skin send a message via nerve fibres, A-delta fibres and C fibres, to the spinal cord and brainstem and then onto the brain where the sensation of pain is registered, the information is processed and the pain is perceived. Fast pain is transported from A delta fibers while slow pain from C fibers.Examples of A delta fiber pain are sharp, prickling and acute pain and C fibers are slow, throbbing, aching chronic pain.

What is the pathway for pain? 

In short form pain starts at nociceptors –> Primary afferent sensory fibers –> Dorsal root ganglion –> Na channels allow depolarization through axons –> Dorsal Horn of spinal cord –> Second order neurons –> Brain.

The General Pain Pathway

Within the pain pathway there are 3 orders of neurons that carry action potentials, signalling pain. First-order neurons are pseudounipolar neurons which have cell bodies within the dorsal root ganglion. They have one axon which splits into two branches, a peripheral branch (which extends towards the periphery) and a central branch (which extends centrally into the spinal cord/brainstem). Second-order cell bodies of these neurons are found in the rexed laminae of the spinal cord, or in the nuclei of the cranial nerves within the brain stem. These neurons then decussate in the anterior white commissure of the spinal cord and ascend cranially in the spinothalamic tract to the ventral posterolateral (VPL) nucleus of the thalamus. Third-order the cell bodies of third-order neurons lie within the VPL of the thalamus. They project via the posterior limb of the internal capsule to terminate in the ipsilateral postcentral gyrus (primary somatosensory cortex). The postcentral gyrus is somatotopically organised. Therefore, pain signals initiated in the hand will terminate in the area of the cortex dedicated to sensations of the hand.

How do we react to pain? 

This can lead to two different responses, fight or flight. In response to the pain stimulus the brain overall increases in “fight or flight” arousal.

– increased sympathetic tone

– increased catecholamine release

– increased metabolism & oxygen consumption (via hypothalamus)

How can you treat pain? 

There are many ways an individual can help reduce pain and manage it. Some people will say to get plenty of rest, distract yourself, or participate in light exercise. However, what happens when these tips don’t help with the pain? Many people reach for pharmaceutical mechanisms to treat what they are experiencing from ibprohpen to different opioids. This occurs by inhibiting nociceptors and dorsal horn pain transmission. 

What are CB1 and CB2? 

CB1 are receptors found primarily on the presynaptic membrane of neurons, ubiquitous. It is coupled to G proteins, causing inhibition of adenylyl cyclase, influencing numerous transcription factors and potassium channels. While CB2 are receptors which are more localized, specifically to immune cells. Both CB2 and CB1 receptors on mast cells participate in the anti-inflammatory mechanism of action of cannabinoids.

How is CB1 involved in pain management? 

The CB1 receptor is distributed throughout the nervous system. It mediates psychoactivity, pain regulation, memory processing and motor control. CB1 is a presynaptic heteroreceptor that modulates neurotransmitter and neuropeptide release and inhibits synaptic transmission. Activation of CB1 results in the activation of inwardly rectifying potassium channels, which decrease presynaptic neuron firing, and in the inhibition of voltage-sensitive calcium channels that decrease neurotransmitter release. Allosteric modulators of the CB1 receptor bind to a distinct site apart from the orthosteric site and produce conformational changes in the receptor, thereby altering the potency of the ligand when it binds to the receptor. No effect in the absence of ligand binding. So, CB1 positive allosteric modulators would be expected to enhance the pain relieving effects of endocannabinoids, but with limited side effects. ZCZO11 reduced neuropathic pain and inflammatory pain without development of tolerance or occurrence of psychoactive side effects.

 

Overview of the circadian rhythm

The circadian rhythm regulation plays a crucial role in people’s healthy lives affected by factors consisting of cosmic events related to the universe and earth, environmental factors, and lifestyles. The circadian rhythm is affected by the circadian clock, which is an internal regulator in cells of organisms, coordinates physiological and behavioral activities with daily environmental variations within 24-hour cycles (Charrier et al., 2017). That’s just a quick explanation of the circadian rhythm but how does adenosine affect this.

 

 

Adenosine overview

 

Adenosine is linked to metabolism of cells. In the central nervous system, an increase in neuronal activity enhances energy consumption as well as extracellular adenosine concentrations. In the brain, adenosine antagonists affects A1 receptors which decreases neuronal activity which is why you have more energy (Porkka- Heiskanen et al., 2002).

 

 

Adenosine and sleep

Out of the many articles I have been reading it seems like the main area of adenosine activity is the cholinergic basal forebrain. It is important in this function because it is an essential area for mediating the sleep-inducing effects of adenosine by inhibition of wake-promoting neurons via the A1 receptor (Basheer et al., 2004). Their evidence finds that a cascade of signal transduction induced in A1 receptor activation in cholinergic neurons leads to increased transcription of the A1 receptor. They believe that this is the reason behind sleep-deprivation.

 

 

Coffee and sleep

The information I found on the effects of adenosine on sleep made me wonder if the time that one drinks caffeine has an effect on certain stages of sleep. A study monitored the effects of drinking caffeine at 0, 3, and 6 hours before going to sleep. The results of this study suggest that 400 mg of caffeine taken 0, 3, or even 6 hours prior to bedtime significantly disrupts sleep. Even at 6 hours, caffeine reduced sleep by more than 1 hour (Drake et al., 2013). This isn’t that crazy since 400 mg is a lot of caffeine but even 6 hours seems like it should be long enough. The caffeine however, only reduced the time between stage 1 and 2 sleep and had no effect on REM sleep. The results did conclude though that this degree of sleep loss, if experienced over multiple nights, may have detrimental effects on daytime function (although more research is needed).

 

 

 

 

Works cited

 

Basheer, R., Strecker, R. E., Thakkar, M. M., & McCarley, R. W. (2004). Adenosine and sleep–wake regulation. Progress in Neurobiology, 73(6), 379–396. https://doi.org/10.1016/j.pneurobio.2004.06.004

 

 

Charrier, A., Olliac, B., Roubertoux, P., & Tordjman, S. (2017, April 29). Clock genes and altered sleep-wake rhythms: Their role in the development of psychiatric disorders. International journal of molecular sciences. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454851/.

 

 

Drake, C., Roehrs, T., Shambroom, J., & Roth, T. (2013). Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. Journal of Clinical Sleep Medicine, 09(11), 1195–1200. https://doi.org/10.5664/jcsm.3170

 

Porkka-Heiskanen, T., Alanko, L., Kalinchuk, A., & Stenberg, D. (2002). Adenosine and sleep. Sleep Medicine Reviews, 6(4), 321–332. https://doi.org/10.1053/smrv.2001.0201

Cannabinoids in the brain

Cannabinoids are popular in both recreational and medical use. The primary active constituent of the hemp plant Cannabis sativa is delta9-tetrahydrocannabinol (delta9-THC). Psychoactive cannabinoids cause enhancement of sensory perception, difficulties in concentration, impairment of memory, along with an extensive list of other symptoms. Recent findings revealed delta9-THC-induced cell death with shrinkage of neurons and DNA fragmentation in the hippocampus (Ameri et al., 1999). The CB1 receptor mediates inhibition of adenylate cyclase, inhibition of N and P-type calcium channels, stimulation of potassium channels, and activation of mitogen-activated protein kinase. Interestingly, cannabinoids share a final common neuronal action with other major drugs of abuse such as morphine, ethanol and nicotine in producing facilitation of the mesolimbic dopamine system (Ameri et al., 1999). This might explain why people call it a ‘gateway drug.’

 

 

THC long-term effects studies

A study found that, cognitive impairments in adult rats exposed to THC during adolescence are associated with structural and functional changes in the hippocampus (NDA et al., 2021). They also found that when that animal is exposed to THC, there is an increased likelihood that the animal will target and self-administer other drugs that effect the same reward system. The studies referenced by the NDA found that some users developed altered connectivity within the brain leading to different cognitive impairments, while other studies found no significant structural differences in the brain. Basically, they have no idea if there is a negative long-term effect in general. However, they do believe that the age that you start using at is a determining factor.

 

 

Gateway drug?

So, if no conclusive results were found on the structure of the brain long-term, what about long term effects on usage. They found that, early exposure to cannabinoids in adolescent rodents decreases the reactivity of brain dopamine reward centers later in adulthood. Although this does not directly conclude the results of a human brain, this could help explain the increased vulnerability for addiction to other substances of misuse later in life. These findings naturally would suggest that marijuana is a gateway drug, however, most people who use marijuana do not go on to use other, “harder” substances. They found that there is also a cross sensational effect within alcohol and other drugs. This means that simply drinking alcohol also heightens your responses to other drugs (NDA et al., 2021).

 

 

What to draw out of this

 

To say that marijuana has no negative effect on the brain would be disingenuous. However, just because the evidence is inconclusive at this point does not mean that it is entirely safe to use. If you use marijuana, cool, but just know there could be risks of future cognitive development in store.

 

 

 

 

Works Cited

 

Ameri, A. (1999). The effects of cannabinoids on the brain. Progress in Neurobiology, 58(4), 315–348. https://doi.org/10.1016/s0301-0082(98)00087-2

 

National Institute on Drug Abuse. (2021, April 13). What are marijuana’s long-term effects on the brain? National Institute on Drug Abuse. Retrieved from https://www.drugabuse.gov/publications/research-reports/marijuana/what-are-marijuanas-long-term-effects-brain.

 

National Institute on Drug Abuse. (2021, May 24). Is marijuana a gateway drug? National Institute on Drug Abuse. Retrieved from https://www.drugabuse.gov/publications/research-reports/marijuana/marijuana-gateway-drug.

Story Time:

I have never experienced a concussion, nor have I ever seen someone I’m close to get a concussion. This statement would’ve been true a year ago, but I can no longer say this is the case. This past March, one of my best friends got a concussion and it was an event I will never forget. I was at this friend’s house, hanging out with her roommates and mine while we waited for her to get off of work. She had been snapchatting us throughout the evening, telling us about the drama going down at work. She had told us that she got hit in the head amidst the drama, but she wasn’t feeling anything more than a headache. She arrived at her apartment 20 minutes later, greeting us but excusing herself to her room to lay down. Almost two hours later, my friend came out of her room, tears streaming down her face as she held a hand to her head. She looked at my roommate and I and asked, “when did you guys get here?” Immediately, our concern skyrocketed. We replied that we had been there since nine o’clock, and she had greeted us when she came in the door. She then proceeded to ask, “how did I get home?” My roommate and I looked at each other, mutually deciding that we needed to take our friend to the emergency room. We continued to ask our confused friend questions about what day it was, what she remembered, and how she was feeling as we prepared her to go. We helped her get her coat on and grabbed her ID before taking her down to the car. I gave my friend a blanket that she could use to block out the lights, and we were on our way to the emergency room.

Upon arrival to the emergency room, I knew my friend’s condition had worsened. My friend was squinting at the light as we stepped out of the car. She was very unsteady as we walked to the front doors of the emergency room—I was essentially holding her up, at this point. At this time, COVID was still a severe problem, so they were not allowing people other than the patient into the ER. However, the person at the COVID checkpoint saw the pair of us and said nothing as I walked my friend to registration. I told my friend to close her eyes as I checked her in, as she couldn’t even remember her birth date. I went to the front desk and told her who my friend was, what had happened, and gave her my friend’s photo ID. A nurse came out with a wheelchair just a few minutes later, and the two of us got my friend seated in the wheelchair. The nurse took my friend to the back, while I waited in my car in the parking lot. My roommate and I were waiting for our friend at the emergency room until 3:00 am.

Post-Concussion Thoughts:

Whenever I thought about concussions prior to the incident with my friend, I imagined how much it would hurt to be hit that hard in the head, but I never thought about the actual injury itself. I never thought about the memory loss, the confusion, the photophobia, or the  loss of balance one may experience after the event. It wasn’t until I witnessed it with my friend that I began to think about all of the conditions associated with concussion. Figure 2 shows a more complete list of concussion symptoms, but I will focus on only a few.

I also have never thought about the biological causes behind these conditions. The migraines, light sensitivity, and sound sensitivity can all be attributed to the ion flux that occurs following a concussion.[1] Ion flux is the movement of ions into and out of the cell. This flux occurs because a concussion makes little holes in the plasma membrane, which allows calcium and sodium to move into the cell and potassium to move out of the cell.¹ A good model for this idea is the sharing of a twin bed. If one person is in the bed, and another joins, the original person is likely to leave (unless they fight for it, but let’s imagine this occurs in a perfect utopian society). This movement of ions can cause depolarization of the membrane, leading to excess release of glutamate.¹ The impaired cognition, slowed reaction times, and slowed processing often seen post-TBI are attributed to impaired neurotransmission and axonal dysfunction.¹ Impaired neurotransmission is an imbalance in the release of excitatory and inhibitory neurotransmitters. There are more excitatory neurotransmitters (action-inducing chemicals) binding to receptors than inhibitory neurotransmitters (action-inhibiting chemicals).¹ The axonal injury is the stretching of the axons of neurons.¹ Like a hair tie that you’ve used one-too many times, the axon stretches out and weakens as a result of the trauma to the brain. All of these things were going on in my friend’s brain, lasting months after her injury. You don’t really think about any of these severe effects from a concussion until you are a witness to it. I will remember this event forever, and I am glad that I am able to connect my friend’s symptoms to biological events going on within her brain.

[1] https://moodle.cord.edu/pluginfile.php/1052900/mod_resource/content/3/2014%20The_New_Neurometabolic_Cascade_of_Concussion.3.pdf

Image 1

Image 2

The obesity rate within America during 2017-2018 sat at a staggering 42.4%. If that wasn’t bad enough, 73.6% of Americans are now considered to be overweight. Look at the chart below, obesity rates within the US have increased exponentially since the 60’s. Several drastic changes occurred during the 80’s within American culture/society that impacted obesity rates, leading to the exceptionally high rates of obesity.

Figure 1

Obesity is associated with many negative health conditions. These conditions cost America anywhere between 147 and 210 billion dollars annually. Will our societal eating habits become so greatly problematic to the point of Wall-E? As a kid I thought the movie was funny, the portrayal of the overweight people seemed to be amusing and unrealistic since there appeared to be a complete lack of healthy humans. However, if Americans continues this trend towards increased obesity, we could end up looking similar to those pictured in this fictional movie. Would I still find it funny, probably not.

Picture credits; Wall-E

One of the changes mentioned earlier that took place in the 80’s relates to the change in meal composition. As a society we are moving away from healthier meals in favor of high fat diets. We talked at length about this in class, there are several negative consequences of eating a high fat diet. You can find that information on this document if you would like to look more into it. As an example of how we’ve changed out consumption of different foods, lets look at a couple of examples. Consumption of vegetable oil within Americans diets has DRASTICALLY increased over time. 400 additional calories are consumed daily due to this one ingredient alone. Unfortunately that is not the only food “category” that has changed. Look below to see examples of three food categories and how their average (daily) caloric intake has changed over time.

Figure 2, 3, and 4

Here is a list of the top calorie sources within the US diet

1. Grain-based desserts (like cakes, cookies, and donuts)

2. Breads made with yeast

3. Chicken and chicken dishes

4. Soda and sports drinks

5. Pizza

6. Alcoholic beverages

7. Pasta and pasta dishes

8. Mexican dishes

9. Beef and beef dishes

10. Dairy desserts (like ice cream and cheesecake)

In case you hadn’t noticed, none of these are overly healthy options and are all very high in fat, leading back to the article relating to high fat diets and how unhealthy that is for us.

The American diet in terms of daily calories has changed over time. Today Americans consume more than 3,600 calories every day which is a 24% increase from 1961 when Americans only consumed 2,880 calories daily. The chart below shows how the US food chain has ballooned over time in order to meet the demands of the consumers. The chart shows slightly different estimates of daily caloric intake, estimates that vary per source, but it shows the shift from 2,880 to 3,600 calories. Sources seem to have conflicting estimates, but almost all seem to agree that daily caloric intake has risen by at least 20%.

Figure 5

What changes have lead Americans to become so obese, especially the large spike in obesity during the 80’s? Well the simple answer includes several things: a change in the composition of meals (for example more saturated fat and vegetable oil), source of food (fast food over home cooking), and lifestyle changes (less exercise and more loungin around watchin the Vikings lose).

In terms of a changing food source, the graph below does a good job showing where families have gotten their food from over the years. Families used to eat at home, now fast food and restaurants compose a much larger percentage of weekly meals.

Unfortunately obesity in America is not only a problem of consumption, it is also a problem of physical exertion. What do I mean by this? Well, most Americans fail to meet the US governments minimum daily recommended exercise. That recommendation includes 75 minutes of vigorous cardiovascular exercise a week as well as muscle strengthening twice a week. Sadly only 23% of Americans achieve this minimal standard. Time is spent doing other things, for example watching television.

Figure 6

Figure 7

With Americans having a higher caloric intake and a decrease in exercise it is not shocking to see a drastic rise in obesity. Lets all get out of our chairs, eat a little better, and work as a society to better our health. If we don’t and our diets continue to contain a high ratio of fat, we might get to a point where our body becomes resistant to both insulin and leptin. This scenario would lead to a detrimental feedback loop that would benefit no one, leading to even higher rates of obesity with little hope for individual health and well being.

Here’s a link to a video of me explaining my topic if you’d rather listen to my voice instead of reading: https://drive.google.com/file/d/1W9P1wZxyiVZsQILe2YTxtd4Sm4rKFIo-/view?usp=sharing

 

Centers for Disease Control and Prevention. (2021, September 30). Adult obesity facts. Centers for Disease Control and Prevention. Retrieved November 16, 2021, from https://www.cdc.gov/obesity/data/adult.html.

Centers for Disease Control and Prevention. (2021, September 10). FastStats – overweight prevalence. Centers for Disease Control and Prevention. Retrieved November 16, 2021, from https://www.cdc.gov/nchs/fastats/obesity-overweight.htm.

Schuler, L. (2021, February 12). The real reason Americans are so fat. Men’s Health. Retrieved November 16, 2021, from https://www.menshealth.com/weight-loss/a19536794/reasons-americans-are-fat/.

” why the world is overweight? the 1980’s and its contribution to our health now! Size Fantastic – Sustainable Weight Control – Healthy Weight Control and Weight Loss. (n.d.). Retrieved November 16, 2021, from https://sizefantastic.com.au/weight-loss-tips/why-the-world-is-overweight-the-1980s-and-its-contribution-to-our-health-now/.