Pain Elective

Can you believe we do actually have some choice in medical school about what we want to do with our precious time and energy? A little bit of choice anyway; four credit hours worth! We have to take non-clinical electives, and have four years to complete them. I took the advice of some third and fourth year students and started taking some electives this year. That way I will have a few weeks of free time during my later years. I figure that a few weeks off from clinical rotations will be worth the extra time and energy that I put in on this end. There are lots of choices that we have, and you get emails all throughout the year for different electives. Some of the choices we have had so far are History of Medicine, Nutrition (I know ,I know how sad that it's an elective), Death and Dying, Healer's Art and many others.

So I have already taken Healer's art (see my entry of Feb 1st), and this week I am starting an elective in medical literature that I will write about later. In addition, I am halfway through on elective on Pain. Every week we are introduced to a different topic on pain (neuropathic pain, migraine, back pain, pain in children, medications for pain), and one of the weeks, we have to do some extra research on one of these topics and present what we have learned to the class. I really, really, really like this elective. There is something about the neural mechanisms of pain that has grabbed my attention, enough so that I don't find it hard to find time to read about it! It's true that when you are passionate about something, you can find time for it no matter what (which is why I don't exercise much - not enough passion to get my butt off the chair).

So I get to present information this week on migraine pain, and specifically, on research that has been done on Botox injection treatment. I'm sure you have all heard of Botox for wrinkles. But have you wondered about what it really is, and how it works? I got to dive into the mechanism in order to understand why scientists are trying Botox for the treatment of both migraines and tension type headaches. Botulilum Toxin A is one of seven different toxins that is produced by a soil bacteria called Clostridium Botulinum. These toxins are the most poisonous naturally occurring substances in the world. (this is also the toxin that causes food borne botulism - which is a medical emergency and can be fatal).

So why would doctors and/or scientists inject this toxin into our body? It's because of the mechanism of action the toxin has on muscles. It's no good in the digestive tract, and it's also toxic to nerve cells, but in a way that has a positive clinical outcome. It works by blocking the release of an important chemical at the junction of your nerves and the muscles they innervate. A normal junction will have Acetylcholine released from the nerve terminal, travel across a gap, and dock onto receptors on the muscle cell membrane. Once Acetylcholine docks on the muscle cell, the membrane opens ion channels, causing the muscle to contract. Botulinum Toxins A and B block the initial release of Acetylcholine from the nerve cell, so that muscular contraction cannot take place.

So for wrinkles, this toxin is injected in the forehead muscles, and the wrinkles will fade away....for about 4-5 months. The nerves are quite resilient, and they grow new terminals that can release the required Acetylcholine for muscular contraction. So what about headaches? Even though there is much controversy over the exact mechanisms of headaches and migraines, there has been documented concurrent muscular tension in the neck and face. While tension does co-exist with headache pain, it has not been demonstrated that the muscle tightness is the actual cause of the headache pain.

So after learning about Botox (which is actually the brand name for the Botulinum Toxin A), and recalling all I have learned recently about migraines, I read the literature, the reviews, and this is what I have found in terms of the efficacy of Botox with migraine pain.

Before I tell you the results however, I need to tell you that there is a lot I have learned about medical studies, and how to determine what is a good study and what is not. You would think that if an article is published in a journal, especially a reputable one, you can trust and believe the results of the study. But this is not always the case. We have to critically read the literature (in our own time) to determine if the study is internally valid (proper selection methods, proper analysis of the data, for example), and also if the study is externally valid, that is, can a physician apply the results to his or her patient population (for example, most studies are done on American white males, so the results may not apply to a female Asian woman in your practice). Just think about this when you hear the newscaster give you the amazing results of some study about blah blah blah. You have no idea how many people were in the study (the more people in the study the more powerful the results), or what type of study it was (experimental or just observational?), or what type of people were in the study, or if there are other studies that have found the exact opposite results. So just have an open mind, and if you are really ambitious, take a statistic class, learn how to read medical literature, or just call me.... :)

So the migraine reviews I read on Botox treatment of migraines and/or headaches separated the different studies into different types of categories, depending on the strength of the study. For example, the "gold" standard study is a randomized double blind study, but there are LOTS of studies that either do not use this type or cannot use this type to test their hypothesis (for instance, you can't do double blind studies on surgical procedures....). Interestingly, the strongest studies on Botox and migraine relief had both positive and negative results. That is, half of the studies showed a reduction in migraine pain after treatment with Botox, but the other half of the studies did not show a significant decrease in pain. (don't ask me to explain statistical significance - I'll be up all night writing about confidence intervals and p values and beta errors). Anyhow, there were many more positive studies found in the lesser categories of the studies (as determined by the reviewers). That is, as the studies were less powerful, there were more positive results found.

So what does all this mean? It just means that it has not been proven that using Botox for migraines is a successful treatment for migraine and headache pain, NOR has it been proven that Botox IS NOT a successful treatment. Isn't that great? After all the money and time and energy spent on all these studies, nothing has been set in stone yet. It seems like some of the problems with the migraine studies I looked at were that there was no standard between the studies for the amount of toxin used, nor were the same muscles injected. Obviously, more studies with a larger amount of patients, and a more standardized treatment approach, are required in order to determine the efficacy of Botox for the treatment of migraine. Fortunately, there are no permanent side effects from the treatment, so no one will suffer needlessly during future studies.

What do you think? Does it make you want to do research? Study statistics? Write a paper? It does for me! (remember I am a true geek at heart). So much, that I have joined forces with a fantastic researcher, Mary Heinricher PhD, who I will work with this summer studying the effects of a migraine medication on cells in the brain stem, but that's a story for later.

Coming Together

I can't believe it's been almost a month since I have written. Needless to say, it's been a rough month. The high I had from my time in the Redwood forest has been erased, only to be replaced with a long to do list and a nagging pain in my abdomen. Yes, the stress is catching up with me. I'm not sure if it's just that I am older, or that the stress of medical school has reached a tipping point, but it sure seems to be taking its toll on my body. Erinna saw me taking my daily regimen of pills (for low thyroid, ulcer, and depression/anxiety) and remarked, "Am I going to have to take so many pills for things when I am your age mom?" I replied, "I hope not, but maybe you shouldn't go to medical school, then your life won't be so out of balance". Then she told me that she had already thrown that idea out of the window, commenting that she definitely did NOT want to study so hard. Spoken with the wisdom of a fifteen year old who cannot spend very much time away from her cell phone, ipod, or computer/my space account. She may change her mind, and she may not.

As for me, I am trying to do what my doctor recommended to me today. Survive. And I am surviving, just not always with a smile on my face. This is a good week though because it is spring break. And what a wonderful break it is! I'm catching up on my sleep, reading some good books, and YES, watching TV. (OK, never mind that I am watching the ER seasons from the beginning....at least I'm sitting on the couch and not studying!). I've also been playing tennis with Erinna everyday, who by the way, has gotten incredibly good since making the Junior Varsity Team at Lake Oswego. Since I can no longer beat her (we used to be equal), she now has to give me "handicap" points so that I don't get too discouraged and give up. Ouch, it hurts my ego! :)

On a serious note, I have noticed that the things I am learning are becoming more personal, and hitting more close to home, as people around me struggle with their health (including myself!).

Now when I take my ulcer medication, I think about what the molecule is actually doing (blocking the proton pump in my stomach), and can picture the mucosal lining that is being eaten away from acid. Gross huh? That vision though, plus the discomfort, helps me to make smarter choices, like not drinking coffee or alcohol.

Then there was the recent death of a sweet old man, Dr Arnold Rustin, who was my mentor and guide for getting into medical school. He died of congestive heart failure, and now when I learn about that in school, I see his face, and think about his heart struggling so hard to pump out the blood needed to sustain his life. I have a signed picture of him next to my dry erase board at home where I study, and I look at his smiling face whenever I feel like giving up. He reminds me to persevere, and also, that I will be a great physician. Even though he's no longer around in body, I definitely feel his spirit.

And now there is also my sick kitty Mango. His kidney's are failing, which is common I guess for older cats (he's 13). And the irony is that we got the diagnosis the very week I was studying renal physiology in school. And so I had to answer Ronando's questions about dehydration, and the inability to concentrate urine, and the toxic metabolites that build up in the blood when the kidneys start to fail. So we have to feed Mango special low protein food, and give him subcutaneous fluids (under the skin with a needle). It's like home hospice care. We make him feel better until his kidneys give out. It could be a month, or a year, depending on how advanced the damage to his kidneys already is. I have so much more patience for him now, letting him crawl onto my lap while I am studying. I realize that mostly what he wants is to be close to one of us at home, curled in a lap at all times.

While these real life medical issues make my heart a bit heavy, they also give me context for the volumes of information I am absorbing in school. It is no longer just words in a book, but it's real people, and pain, and my loved ones, all wrapped up in moments squeezed in between the hours in lecture and the library. I am so incredibly grateful for these lessons, and for waking up every day to learn anew.