Probing clues to Alzheimer's; treating chronic pain: Upstate Medical University's HealthLink on Air for Sunday, Nov. 20, 2022

Host Amber Smith: Coming up next on Upstate's "HealthLink on Air," a computational neuroscientist shares his role in researching Alzheimer's disease.

Chris Gaiteri, PhD: ... Combining the activity of the brain with gene and protein information is something that I'm really interested in right now because we have the ability to do that because we're scanning people relatively soon before they die, and then we have their tissue after they die. ...

Host Amber Smith: And an anesthesiologist who specializes in pain management talks about methods for dealing with chronic pain.

Vandana Sharma, MD: ... Most people do not like the feeling of pain. It has these two components, that is, sensory and emotional, and sometimes tissue injury is involved, and sometimes it's not. And this is especially true for chronic pain. ...

Host Amber Smith: All that, some expert advice about carrots and your vision, and a visit from The Healing Muse, coming up after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine with the experts from Central New York's only academic medical center. I'm your host, Amber Smith. On this week's show a pain management specialist talks about how chronic pain is treated. But first, a computational neuroscientist discuss theories about how Alzheimer's disease develops.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

Many, many mysteries remain to be solved about the development and progression of Alzheimer's disease. Today I'm talking about where things stand with computational neuroscientist Chris Gaiteri. He's an associate professor of psychiatry and behavioral sciences at Upstate and the newest Empire Innovation Scholar, and his research focuses on Alzheimer's. Welcome to "HealthLink on Air," Dr. Gaiteri.

Chris Gaiteri, PhD: Thanks, Amber. Happy to be here.

Host Amber Smith: You're a computational biologist. What does that have to do with curing Alzheimer's?

Chris Gaiteri, PhD: To cure Alzheimer's, what we expect is that we're going to have to process some big data related to the brain. And you're probably more used to hearing big data in the context of large tech companies, but actually we have big data on the brain and Alzheimer's disease, and so you need people like me to do math and statistical processing of that data in order to sort of extract key signals that are actually going to be the things that we're going to need to monitor and and treat in Alzheimer's disease.

Host Amber Smith: So your doctorate is in neuroscience. For the work that you're doing on Alzheimer's, do you team up with medical doctors on your various research projects?

Chris Gaiteri, PhD: Some of my closest colleagues are MDs. Some of them see patients. Some of them see patients and do research. Some of them are fully in research. But they're great to work with. And I think in general they're very motivated because a lot of them come from this background of just they can't handle telling patients, "there's really very little we can do for you." So that's driven them to research. So they tend to be really highly motivated individuals, and they're great to work with.

Host Amber Smith: Now, in your work, you're searching for what changes happen inside the brain that lead to Alzheimer's, is that right?

Chris Gaiteri, PhD: Exactly. There are a few big studies that generate a lot of our data. These are studies where older people volunteer. They sign up to be studied. And we'll give them cognitive tests every year. We'll monitor things like their diet and their stress levels. And once they pass away, many of these people have volunteered to donate their brains, and so, you're exactly right. Once we have those brains and we know the history of these people, we can then look at molecular and cellular things happening inside those brains and compare them between people with Alzheimer's and people without Alzheimer's.

Host Amber Smith: For years, we've heard experts blame "plaques" and "tangles" as responsible for Alzheimer's. Can you explain to us what those are and whether they play a role at all?

Chris Gaiteri, PhD: Sure. They were discovered about 100 years ago by Alois Alzheimer, who is the doctor that the disease is named after. And the plaques are a buildup of protein that occur outside of your neurons, outside of your brain cells. And the tangles you can picture as pretty much what it sounds like, a tangle of yarn, but that tangle is going to be inside of the cell. And both of these contribute to Alzheimer's disease. In fact, to have Alzheimer's disease, you need to have a post-mortem examination of the brain, and you need to find both of these to really have a definitive Alzheimer's diagnosis. A lot of times people will, their doctor will say, "Oh, you have Alzheimer's." That's not actually definitive without this post-mortem examination, where you actually observe plaques and tangles in the brain.

Host Amber Smith: So do the plaques and tangles cause Alzheimer's, or are they a symptom of it?

Chris Gaiteri, PhD: When we measure plaques and tangles, they can explain about 30% of the dementia that we observe. They can explain about 30% of cognitive decline. So they're clearly an important component, but there's also clearly other things that are leading to dementia, which is what we really care about, right? We don't care how many plaques and tangles you have in your brain. We care about can you function in society? Are you having a good life in your older years? So they're a component of the cause. But the evidence suggests they're not the entirety of the cause. The reason that we're so focused on those has to do with some very rare genetic mutations in the genes that lead to plaques and tangles. And, in this very rare case, you get a very severe and early form of Alzheimer's disease. So that's really where the focus on them as a cause has come from. But in the broader population, there's clearly many other things which are contributing to causes of dementia.

Host Amber Smith: Do you have your own hunches about what is causing dementia?

Chris Gaiteri, PhD: So I have hunches, but they're really driven by data. It's not just that I'm pulling these things out of the air. We do have some additional mechanisms that we -- the royal "we," myself and others -- are investigating, in experimental labs where we'll use CRISPR (genome editing technology that's short for Clustered Regularly Interspaced Short Palindromic Repeats) will use genetic tools to engineer cells to modify these mechanisms and then see if we can sort of recapitulate Alzheimer's in a dish. That's kind of how we're investigating these new causes. So yes, there are some things on the horizon that we're testing that I think are very interesting.

Host Amber Smith: So you mentioned genes as a potential cause of some types of Alzheimer's. How often does Alzheimer's run in families?

Chris Gaiteri, PhD: It's very rare for the inevitable form, what we call familial Alzheimer's, to run in families. It's a very rare situation. Typically in that case, you'll have this genetic mutation that essentially guarantees you'll have Alzheimer's disease. And that's a very rare situation. When that happens, you get Alzheimer's disease at a significantly younger age, even as early as 50, or slightly younger. You'll begin seeing symptoms, whereas typically you'll be 65-plus, 75-plus, where you would typically have normal Alzheimer's symptoms, the general form of Alzheimer's disease. So it's really rare to have this genetic component of Alzheimer's disease. However, there are hundreds of genes that give you a little bit of risk. So when we're talking about familial Alzheimer's disease with a strong genetic driver, that's a single genetic mutation that's doing the work there. In general, there is a genetic component to Alzheimer's disease, but it's much more distributed across the genome where hundreds of genes are contributing a little bit, which makes it much harder to predict because you have to aggregate across the entire genome. And even then it's sort of a much fuzzier, more difficult-to-predict situation.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith. I'm talking with computational neuroscientist Chris Gaiteri, the Empire Innovation Scholar in Upstate's department of psychiatry and behavioral sciences.

So, how did you get into the field of neuroscience?

Chris Gaiteri, PhD: I remember back in high school thinking that I wanted to study something where I would never be bored, and I had this vague idea that the brain sounds pretty complicated. That would be an interesting thing to study for the rest of my life. And, that turned out to be true. I'm sure there are many other fields which are also equally interesting, but for me, I wanted something where there'd always be something new. There would always be something that we don't understand. And, neuroscience has turned out to fit that bill.

Host Amber Smith: What led you to focus on Alzheimer's?

Chris Gaiteri, PhD: That's somewhat of a more pragmatic issue. I'm interested in treating a variety of mental illnesses and diseases, in particular the ones that affect society the most, that are the most common, that are the most severe. And Alzheimer's is right at the top of the list. And also pragmatically, fortunately, recently there's been a large increase in funding for research in this disease. So it makes it actually feasible to study that disease as opposed to some more rare or neglected diseases where there just isn't the funding to actually study them.

Host Amber Smith: I'm curious about how you analyze or you look for the genes or proteins or molecules that are responsible for Alzheimer's. You mentioned some people, when they die, they donate their brains to research. So at some point someone's working on tissue, or blood samples. Are there imaging scans involved? I mean, what else is done to help you look for these genes and proteins and molecules?

Chris Gaiteri, PhD: You're right, there's definitely tissue involved. There's a large freezer farm. I can remember walking through 80 freezers in a long hallway full of brains of people who have donated their brains to Alzheimer's disease research. So it's really great to have those resources. One thing we have done also, as you suggest, is we give yearly or every other year, brain scans to individuals who are in these studies so that after they pass away we have a really nice three dimensional image of the brain, and we also do fMRIs (functional magnetic resonance imaging) so we can look at the activity of their brain as well. So combining the activity of the brain with gene and protein information is something that I'm really interested in right now because we have the ability to do that because we're scanning people relatively soon before they die, and then we have their tissue after they die. So we can actually combine those together, which I think is going to give us a better, more unified, more effective kind of practical definition of Alzheimer's disease.

Host Amber Smith: Did you first have to learn what brain changes are normal as we age? And, is there a consensus in the scientific community about that?

Chris Gaiteri, PhD: That is relevant because while dementia and Alzheimer's are not part of normal aging, you basically almost never see them in younger individuals, right? So there must be something about the aging process that sort of primes the brain or puts it in this position where it can transition into Alzheimer's and dementia. So yes, there are a couple of projects that actually study gene expression prior to getting Alzheimer's disease. But one of the real challenges is that you can only get one time point from the same brain. So we'd really like to follow people when they're 40, 45, 50. I would love to have brain samples from the same individual multiple times, but that's simply not possible to obtain. You can't just sample from the brain.

So what people will typically do to try to study normal aging and the transition into Alzheimer's is to look at blood, specific cells in the blood, or potentially sometimes you can get cerebrospinal fluid by doing a spinal tap. Of course, that's somewhat unpleasant to do, so it's difficult to obtain that kind of data from the same person over time. So what we have to do is sort of a cross-sectional design where we look at many, many people, sampled at one point of time. But it really does make it difficult to do the sort of study that you're talking about, where we study normal aging and the transition into Alzheimer's disease.

Host Amber Smith: Do you have any ideas about whether inflammation plays a role in the development or the progression of Alzheimer's?

Chris Gaiteri, PhD: Yeah, inflammation has really been a recent sort of star of Alzheimer's research. Back in 2010 when they started doing some really large genetic studies of Alzheimer's disease, multiple genes that were related to microglia, sort of a major inflammatory cell type in the brain, showed genetic variations that were associated with Alzheimer's disease. In particular, there's one called TREM2, where they found in this Icelandic population, which is a really sort of genetically isolated group, you could have a mutation in this inflammatory gene that gave you, reduced your likelihood of having Alzheimer's disease by a third -- which is a big effect for a single mutation. So there's a lot of strong genetic evidence, and genetic evidence is very strong, for inflammation involvement in Alzheimer's disease.

Host Amber Smith: There are several drugs on the market that help people with symptoms of Alzheimer's. So I'm curious about how helpful those are. I'm thinking of medications like Aricept that supposedly support communication between nerve cells. Does that really work?

Chris Gaiteri, PhD: We'd really like a drug that would strike at the causal basis of the disease that would shut down the process that's causing the disease or contributing to the disease. And like you say, these are more about limiting some of the symptoms. So you can have diverse symptoms in Alzheimer's disease, on other than memory loss. You can have agitation and psychosis. You can have a variety of sort of psychiatric symptoms, depression that go along with Alzheimer's disease. So these drugs are more focused at sort of suppressing some of those things. Which is great. But at the same time, they're not that much more effective than placebo and it's also fairly common to have some unpleasant side effects from these drugs as well. So I think for those reasons, that's why when someone comes into the clinic with Alzheimer's disease, it's certainly worth a shot in many cases, but that's why we're not particularly excited to be prescribing these drugs.

Host Amber Smith: The FDA narrowly approved a drug called Aduhelm that's designed to remove amyloid from the brain. It was sort of a controversial move, and it's a very expensive drug. What do you know about that and how well it's working?

Chris Gaiteri, PhD: Yeah. You mentioned it was controversial, and what happened was, there's a committee of scientists that advise the FDA on their perception of the evidence for drugs. And usually that committee of scientists and the FDA are very much in sync. Three very famous scientists resigned from that committee after the committee recommended against the drug and the FDA approved it. So that's unusual. And I think it signals some of the concerns about the cost benefit analysis for the drug, not just in terms of the monetary cost, but in terms of some concerns about side effects that the drug has. So, on the one hand, it's great to be having new drugs approved for Alzheimer's disease. That's what we want, right? But on the other hand, it would be better if they had larger effects and weren't so controversial, and it wasn't so much of a close call.

Host Amber Smith: Do scientists think that if we had a drug that removed the amyloid or the plaques and tangles we talked about earlier, would that fix the problem, or not?

Chris Gaiteri, PhD: So these drugs do remove them. Part of the issue is, though, perhaps they're removing them too late. And so perhaps we need to be intervening earlier in the disease and therefore preserving some of the synapses, some of the connections between nerve cells. So that's been sort of the rejoinder to some of the weaker clinical results is, maybe this is the right thing; we're just not delivering it soon enough. And so that's why in a lot of clinical trials, they're focused on people with MCI, with mild cognitive impairment, which is often sort of a precursor to full-blown dementia, the idea being that that may be a more fruitful time for these interventions.

Host Amber Smith: Researchers are still trying to figure out and agree on the cause of Alzheimer's disease, obviously. I wonder if you have theories about what determines whether Alzheimers progresses rapidly or slowly in the individual.

Chris Gaiteri, PhD: So there are a number of factors that can make you resilient to Alzheimer's disease, meaning that for the same amount of plaques and tangles that someone might have, you're actually doing better than they are. And so the question is, that's sort of a factor that would slow the progression of the illness. It would give you a slower rate of decline. And so, what are those things? And, yes, we actually have published papers on what these factors are, and we're doing experiments on them because there is a lot of variability in terms of the outcomes of having plaques and tangles, in terms of having classic Alzheimer's disease in your brain. And so, if we can essentially give everyone a really slow decline, as opposed to a really fast decline, that would be wonderful. And there is that kind of natural variability in the human population. So that is one thing we're studying.

Host Amber Smith: Alzheimer's is just one type of dementia. Do you think your work might shed light on other types of dementia as well?

Chris Gaiteri, PhD: I hope so.

It would be great to have communication across the discipline. It can be challenging, though. So for instance, with traumatic brain injury, which can lead to dementia, a lot of times it really depends sort of exactly the physics of how a particular brain has been impacted. So each case, to an extent, is somewhat sort of unique. And so even within that class of injuries, it's difficult to draw some universal conclusions. And so then to draw universal conclusions between classes of diseases can be challenging, but it's certainly something that we should try to leverage if we can to work together and draw some robust conclusions.

Host Amber Smith: Do you see similarities between dementias and other brain disorders? You mentioned traumatic brain injury.

Chris Gaiteri, PhD: Yes, there are some similarities, a lot. They won't be full blown similarities, though. What I mean is, for instance, you could have inflammation being involved in multiple brain diseases, but we know that inflammation is probably just one component of Alzheimer's disease, and there'll be additional components of Alzheimer's disease. So I feel like there's selective ways in which we can learn about disease mechanisms across brain diseases. We can import knowledge from a specific domain and use that even if we can't import the entire sort of conceptualization of the disease. There's always spots where we can learn.

Host Amber Smith: You mentioned how you work with big data, and you're sort of focused on the cause of Alzheimer's or the treatments for it. Might there be big data that could let us look at possible preventives for Alzheimer's?

Chris Gaiteri, PhD: Yes. I think that's very important to do because it's likely going to be easier to prevent a disease than to reverse a disease. And I think the public's particularly interested in looking for something preventative for Alzheimer's disease. So it makes sense to the public too, right? In particular, they're interested in is there something in my diet that I can eat that's readily available that's going to prevent Alzheimer's disease? And so I think that that's pointing to some of these studies that are coming out recently about the Mediterranean diet. A lot of times people have shown that you have lower rates of dementia in people who have certain diets, but you never know if it's just due to genetics or the environment or actually what the people are eating. So there's some studies now where they actually do interventions, where they specifically ask people to eat more of a certain type of food and they verify that the person is, in fact, eating their broccoli or whatever the intervention is. And so I think those studies are going to be quite interesting in terms of prevention for Alzheimer's disease.

Host Amber Smith: The field of study you've chosen is just fascinating. I wonder, have you discovered anything that was totally shocking to you about Alzheimer's?

Chris Gaiteri, PhD: So a number of years ago, there was -- this wasn't my finding; this is research by other individuals -- but this finding that plaques and tangles cannot account for a majority of the dementia that we observe in people with Alzheimer's disease. And so I think on the one hand it's discouraging that plaques and tangles are probably not enough. But on the other hand, they've been so difficult to treat that it's really nice to know that there's this unknown cause of dementia out there, and maybe that's going to be easier to treat. And so that's one of our major focuses is trying to nail down what exactly is that signal, right?

We've measured it. We have cognitive tests from people with Alzheimer's disease. We have their brains after they die. So it is possible to actually find molecular causes related to this dementia that's not accounted for by plaques and tangles. And so, going after that is really sort of exciting, and it's been a little bit shocking how big of an issue that is, but at the same point, I'm really happy to be going after something that important.

Host Amber Smith: Well, Dr. Gaiteri, I really appreciate you making time to tell us about your work. Thank you.

Chris Gaiteri, PhD: My pleasure.

Host Amber Smith: My guest has been computational neuroscientist Chris Gaiteri. He's an associate professor and Empire Innovation Scholar in Upstate's department of psychiatry and behavioral sciences. I'm Amber Smith for Upstate's "HealthLink on Air."

Next on Upstate's "HealthLink on Air" -- treatment options for chronic pain.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." People who live with chronic pain know how debilitating it can be. Today I'm talking about management of chronic pain with Dr. Vandana Sharma. She's an associate professor of anesthesiology and the director of pain medicine services at Upstate. Welcome to "HealthLink on Air," Dr. Sharma.

Vandana Sharma, MD: Thank you, Amber.

Host Amber Smith: Let's start with a definition of what chronic pain is. Does pain have to exist for a certain amount of time before it's considered chronic?

Vandana Sharma, MD: Amber, let me start with what is pain, and then we'll move on to chronic pain. So pain is an unpleasant sensory and emotional experience that may or may not be associated with tissue injury. So, I emphasize three things in this, when I talk about pain. It's unpleasant, it's sensory, and it's emotional. So it's not "or," it's "and" emotional. And it's an experience. So the parts of it are, most people do not like the feeling of pain. It has these two components that is sensory and emotional, and sometimes tissue injury is involved, and sometimes it's not. And this is especially true for chronic pain.

So when we say chronic pain, it has gone longer than 90 days, or 12 weeks of time. When acute pain persists for this much of duration, that's when we classify it as chronic pain. Now the majority of the times with acute pain, there is usually a preceding injury. But when it comes to chronic pain, a lot of times the preceeding injury might have healed by that time, but the patients may still be reporting pain. It's not like they're just reporting, they're actually feeling pain. They're experiencing that unpleasant feeling that is debilitating, sometimes to the extent that it inhibits them from doing their routine work or their work-life balance and all those things. So, just to emphasize the fact, again, that tissue injury may or may not be needed for pain to occur.

Host Amber Smith: So if there's not a tissue injury, is pain sometimes tied to illnesses?

Vandana Sharma, MD: A very good question, actually. So when I talked about pain not being associated with tissue injury, in medical terms we call it central sensitization, or wind-up phenomenon. What happens is that pain pathways are not very simple. Like, there are several associations. A very simplistic definition of the pain pathway would be that you get injured in the periphery, and then the pain travels from the periphery to the spinal cord, from spinal cord to the brain. And this is the very simple form of the pain pathway.

What people do not understand is that over a period of time -- and this time, what I'm talking about of 90 days or 12 weeks -- is when several other processes actually come into play, which modulate pain, or which may sometimes increase the pain and sometimes decrease the pain. These pathways happen in the periphery, what we call peripheral sensitization, or they could happen at the spinal cord level, what we call central sensitization, or in the brain. Again, central sensitization. The role of these is to modulate and make the person feel or adapt to the pain. But sometimes, this amplifies pain. So the brain may be erroneously sent signals that I'm still feeling pain even though the injury has subsided. But these erroneous pathways that have developed keep sending signals of continued pain to the brain.

Host Amber Smith: So some chronic pain is not the result of a physical cause?

Vandana Sharma, MD: Or you can also say that the physical cause cannot be ascertained. For example, a person had a sprain that they did not pay attention to at that point. Like, sometimes, minor injuries happen that may just escape your attention. But then over a period of time, the same person may continue to have pain in the foot that may be associated with some other signs like redness or swelling or color changes or temperature changes, or something that we call sympathetic involvement, sympathetic pain involvement, which may, in unfortunate circumstances, it may progress to become a condition called complex regional pain syndrome, where when you ask the patient going back into the history, how did it happen? And they may not be able to give you a succinct answer. "I don't know. All of a sudden I had this foot pain. I can just tell you maybe four, five, six months ago as I was playing, I don't remember if I hurt myself or if I injured a nerve or anything. But since then, the whole foot hurts. And now this is expanding to involve the leg or the knee, and I'm in constant pain."

So those are some of those examples when they may not remember that there could be a tissue injury. Or sometimes, as I said earlier, that tissue injury may have happened. It may have completely healed. But the pain continues to happen. And one such example would be post-surgical pain. When surgeons did their best to treat the cause of pain, whether it was abdominal pain or it was spinal related pain, the cause of pain, like compression of the nerve or pressure on the spinal cord has been relieved. But the patients may continue to be in even more severe pain than than the first place that they went for surgery. So how do we explain pain like that? And that's why when I said that pain is not a black and white area, it's a gray zone where there are a lot of associations with the peripheral organs as well as with intricate neural connections that develop over a period of time in the periphery, in the spinal cord or even in the brain.

To elaborate this a little bit further, I would say that even in the brain, there are several areas, like thalamus is one of the areas that is involved with sensing pain or is the antenna for pain in the brain, for pain signals in the brain. It has connections with several other areas like prefrontal cortex or the cingulate cortex, which are also involved with emotional pain.

So in a very interesting study, functional MRIs (magnetic resonance imaging) were done on people who didn't have any physical pain, just emotional pain, like separation, like any kind of emotional stressors that happened during the life. And the same areas that actually lighten up the areas of brain causing pain are also the areas that are lighted up with emotional pain. So that tells you that physical pain and emotional pain are so commonly intricately related. And that's why this biocycles physical model of pain, where not just are the biological markers, like the tissue injury, that plays a role in pain, but also there are the psychological markers and the social markers that affect pain.

Some of these that I would like to highlight are preexisting stress, or psychological conditions or psychiatric conditions like anxiety and depression. They may or may not be predecessors of pain, but they are so closely related to pain that it's hard to dissociate them after a period of time. Closely associated also -- sleep deprivation, or fatigue. When people who are sleep deprived, they all of a sudden feel way more pain than on the days when they're more relaxed or had a restful night. So it has it's like a vice versa, like a two-way phenomena that happens with sleep and pain. Similarly with emotional situations that I described earlier and pain, what leads to what is hard to say, but they are so closely intricately related to pain that you need to treat the whole thing rather than just treat the biological cause of pain. Otherwise you will be massively unsuccessful.

Host Amber Smith: Upstate's "HealthLink on Air" will be back after this short break.

Welcome back to Upstate's "HealthLink on Air". This is your host, Amber Smith. My guest, Dr. Vandana Sharma, has been telling us about treatment options for chronic pain. She's an associate professor of anesthesiology and the director of pain medicine services at Upstate.

Does medical management work for some people with chronic pain?

Vandana Sharma, MD: Absolutely. When I see patients, I tell them I'm going to offer you three treatment pillars. The most important one of them is physical management, which is treating your biomechanics of pain using physical therapy, using chiropractor care, using acupuncture, TENS unit (transcutaneous electrical nerve stimulation,) like, many different alternative techniques. Second is the medication, which is as important as physical therapy is. And third is the spine injections.

So moving on to your question about medication part, we involve several different kind of medications to treat pain. As more and more research is growing into pain, pain medicines that help treat pain, we see that there is a wide role of medications like anticonvulsants, which are primarily used to treat seizure disorders. But they also have a great role in treatment of nerve-related pain, such as gabapentin and pregabalin. We also use other pain medications such as antidepressants. So a lot of times patients have questions: "Isn't this a drug for depression?" But the doses that are used for pain management are much different from the ones that are used for depression doses. And they have, actually, the widest variety of evidence for these medications that they have a significant role in treatment of pain. These drugs include tricyclic antidepressants such as amitriptyline or nortriptyline, some selective serotonin reuptake inhibitors, SSRIs, what we call like Cymbalta and SNRIs. So these drugs are commonly used for treatment of pain, in addition to over-the-counter drugs like NSAIDs, like ibuprofen and Advil or a widely, commonly used household medication, acetaminophen. All these drugs in combination have a role in modulating pain at several levels, for example, by reducing the inflammation or by reducing the neuro transmission of pain from periphery to the brain as anticonvulsants and antidepressants do. They also help with the negative feedback loop of pain like the descending inhibition of pain. And the most important ones among these are the anticonvulsants because they work in your midbrain level as well as they stop the processes of association of pain with other parts of the brain, such as midbrain and higher up. So, they work by this modulating the descending inhibition of pain.

Host Amber Smith: So it sounds like there's many alternatives to opioids.

Vandana Sharma, MD: Absolutely. Yes. I forgot to talk about opioids because our clinic tries not to go to that option right away, and that's why. It's not used as a first line, ever, especially in nonmalignant pain. Sometimes -- as I just forgot it here -- I forget it in most of my patients when it comes to nonmalignant pain because it's not something I would like to offer as first line, second line or even third line, sometimes, for chronic nonmalignant musculoskeletal spine pain or limb pain and all that. As we have more and more research coming up regarding the mechanisms of opioids, how they work and how they modulate pain and their longer lasting effects on pain management. Our patients who are treated with these drugs for a very long time, we see that the harms that are caused by these drugs are way more than the benefits.

With that said, these drugs are an important tool in a pain medicine physician's wide plethora of medications that they could use for these patients and should never be not given when they're actually indicated because they are one of the strongest pain medications that we have available, moreso to treat acute pain for cancer pain-related problems, as well as for chronic pain that is not being controlled by everything else and significantly impacts the quality of life of the patients. And when I say these things, these are the things that we actually used to monitor the use of opioids, as well, over a period of time. For example, if a patient where I have tried everything else, the three pillars that I talked about, I've used all of them, and nothing has really worked, and it's just short of surgery, or sometimes surgery has already been done, or an 80-year-old who's not a candidate for surgery, but their quality of life is so much impacted by pain that you would actually want to start a monitored opioid regimen in them.

And by monitored, I mean we like to make sure that there's a pain agreement where patients understand what are the risks of starting these medications, not even continuing. Like, what are the risks that you could be exposed to? A lot of education on opioids unfortunately comes from friends and relatives in these patients, where people may be like, "Oh, my doctor gave me this hydrocodone, and it worked great. Why don't you ask your physician for that?" without understanding that taking this medication even sometimes for longer than few days, could put you at higher risk for grave problems such as addiction, dependence, tolerance and something we call opioid induced hyperalgesia, where your body may respond very differently, to acute pain if at any point, if you're subjected to that. And it may be very difficult to control acute pain at that point if you have been chronically subjected to opioids for a period of time.

So all these things need to be discussed with the patients before we even start them on opioids. Make sure that they actually understand that there are risks, and I am actually inducing changes in my receptors, in my pain receptors in the body, in my spinal cord, in my brain, and my coping mechanisms that could be affected by these medications. Once we realize that the risks are actually lesser and the benefits are more, that's when opioid medications can be initiated -- under a very strict monitoring regimen, which includes regular urine drug tests, discussions about how the quality of life has changed, whether there are certain things that couldn't be done before starting these medications that now can be done, and making sure that patients are taking these medications in the best possible way, that does not include a harm to them or their family members.

Host Amber Smith: Can you tell us more about the spinal injection option?

Vandana Sharma, MD: Absolutely. So spinal injections, most of the times, we restrict these to when the etiology of pain is coming from the spine. And by spine I mean the common ones are the chronic back pain or chronic lumbar pain and cervical pain, which is neck pain. Let me talk more about the lumbar pain first. So, there are several sources of pain, and these injections are actually targeted to treat the source of pain. And the sources of this pain could be coming from the pinched nerve or pressure on a neural element in the spinal canal, whether it's in the neural foramina where we call spinal nerve root, or in the center of the spine, what we call spinal stenosis, whether it's central or neural foraminal stenosis. Sometimes the pain that is mediated by facet joints in the back, or a sacroiliac joint. All these etiologies of pain can be treated by targeted injections at these levels. For example, epidural steroid injections that can be placed targeted in the area of pain for conditions such as spinal stenosis or herniated discs, or chronic degenerative changes in the central spine.

They can also be used in a more targeted way that is using a transforaminal epidural steroid, where we put that along the nerve foramen where the nerve roots are emerging from the spinal cord, if we know that that particular nerve root is the cause of the pain. So we deposit the steroid, under X-ray guidance, very closer to the area from where the nerve root emerges, what we call neural foramen. These are called trans foraminal epidural steroid injections.

The other things, as I mentioned, facet interventions, done to treat facet joint related pain, or sacroiliac joint related pain. These are also steroid injections that are used in this area. These can further be followed by more advanced techniques like radiofrequency ablation of these nerves, where the smaller nerves, not the nerve roots but the smaller nerves targeting the joints can be -- the term I commonly use with the patients is we don't burn the nerves. We actually cause changes using heat around these nerves so that the nerves are deactivated for a period of time, which is usually between four to six months. In some patients, it may last longer than six months, up to nine to 10 months, and gives them pain relief for that period of time.

Host Amber Smith: So, the injection is not necessarily meant to be a permanent fix, but it could last several months?

Vandana Sharma, MD: Yes. the injection is not a permanent fix. It's basically using the steroid for its anti-inflammatory activity. Pain is, usually the cause is inflammation. So when there is inflammation in an area of body, that's what creates or causes pain. Here we are talking about tissue injury, not the causes of pain where tissue injury is not involved, but where we know that the disc is the cause of pain, or pressure on the nerve is the cause of pain, or arthritis in the joint is the cause of pain. And all these are inflammatory conditions. And steroids, from their inherent effect on those inflammation areas, can help subside the inflammation and relieve the cause of pain. But inflammation happens again because steroids only work for a period that could be variable from six weeks to 12 weeks. And after that, in a smaller subset of patients, we see that the pain control may linger on for longer.

It also depends how the patients utilize this time. And that's what I tell the patients, that this is the bonus period that you're getting for six to 12 weeks where you could modify your activity levels, where you could use everything else that can be used to treat pain. For example, people who are not able to do physical activity or cannot go to physical therapy or could not do chiropractor therapies, this is your golden period where your pain is lessened to some extent, and you could perform in physical therapy better. Because in the end, it's the muscle deconditioning and your postural changes that are major contributors to your pain. So anything that helps you to correct those problems, just for a period of time, would help you perform better in physical therapy, would help with muscle strengthening. And maybe you don't need the second injection again, because now you're used to the lifestyle changes. That can be done. Or occasionally you need them once or twice a year -- again, when the pain goes out of control -- to help you assist with these training programs for your biomechanics of the spine.

Host Amber Smith: When would surgery be an option for chronic pain?

Vandana Sharma, MD: Unfortunately, surgery is an option sometimes. Usually I tell my patients when all the other nonsurgical options that we are trying for pain have failed, then I send them for a referral to the orthopedic spine or neurosurgical spine (specialists) and see whether they think that this patient would benefit from surgery at that point. That's when we do that. And again, most of the times it's like a consultation between the two services that goes back and forth, where it's like, "Are there any injections, any other injections you could do?" or, "These are the commonest things that are expected after surgery," or "Surgery may not be just a simple thing like a discectomy or a microdiscectomy. It may involve a much bigger surgery."

And the surgeons are pretty open to all those suggestions at that point, where they may be like, "probably go on with the injections for a little longer, probably continue with physical therapy for a little longer, because the surgery may be more extensive than we think," and gives another extra option to the patients what they would want to do at that point or opens up their knowledge about their pain condition, what is causing that and what are the things that could be used, whether they want to come back to the injections, if they were helping to some extent, in combination with physical therapy, or they would want to just go ahead with the surgery where the root cause can be fixed, or at least tried to be fixed.

There are no guarantees, though, with surgery. And sometimes, patients may have to wait for several months for the healing process from surgery to happen before they can actually see the response. In certain situations like cauda equina (in which roots of the lumbar and sacral spinal nerves form a bundle in the lowest part of the spine) or sudden pressure on the spinal cord or spinal canal, where the pressure needs to be relieved, like decompressive surgeries. Absolutely they're needed as emergent procedures. However, in chronic pain conditions, what we see routinely in the pain clinic, where surgical consultation actually just opens up another source where the patients can be sent to see, like, this is when I would need surgery. Until then I'm going to continue with my injections or continue with my medications and physical therapy.

Host Amber Smith: We sometimes hear about patients whose chronic pain does not get better. Do you care for patients who are able to get back to their regular lives, living pain free? Does that happen?

Vandana Sharma, MD: It absolutely happens. And again, as I initially started with the emotional component of pain and how much there is a psychological dependence that is associated with pain. So, using a comprehensive, multimodal, holistic approach to pain when we utilize physical therapy, when we utilize psychological the like cognitive behavioral therapies and biofeedback, optimizing the medications, optimizing the physical level, the deconditioning and the biomechanics of spine, and then utilizing injections judiciously when they're absolutely needed, and then sometimes going to more advanced technologies like neuromodulation can actually help these patients lead up, I wouldn't say a completely normal life, but at least a life that can be as close to normal as possible, where they could do the routine activities and all those things.

It also depends upon your approach as a patient as well, how much invested you are into your pain treatment, how much you want to get better. And obviously everybody wants to get better. Everybody wants to lead as much of a normal life as possible. But then trying to incorporate all these different techniques to get the pain under control are helpful rather than just relying on one thing or the other.

One more thing I want to highlight is social support, presence of family members close by, if that is at all possible, plays a long role in the management of pain. Studies have shown that patients who have a strong social support network, whether it's through their own family or through the friends or even the online networks that are available to offer social support among the chronic pain patients, all these things go a long way in management of pain.

Host Amber Smith: Dr. Sharma, thank you so much for making time for this interview.

Vandana Sharma, MD: Thank you. Thank you for having me here, and it was a pleasure talking to you, Amber.

Host Amber Smith: My guest has been Dr. Vandana Sharma. She directs the pain medicine services at Upstate. I'm Amber Smith for Upstate's "HealthLink on Air."

Here's some expert advice from ophthalmologist Dr. Mark Breazzano from Upstate Medical University. Does eating carrots keep eyes healthy?

Mark Breazzano, MD: Carrots can help keep eyes healthy. However, it is in moderation, like many other vegetables that are part of a nutritious and balanced diet. Some of it has been overhyped, a little bit. And some of the history of that actually dates back to World War II, where the British Air Force actually had radar technology that was helpful against the German Air Force. And unbeknownst to the Germans, they were actually able to fight them off and keep Britain safe. And, as part of this effort in keeping the morale high for the Allies, they attributed it to the "cat-eye vision" that the British pilots had -- and they had easy access to carrots and planting carrots. So instead of eating things like ice cream and of that sort, they were actually eating lots of carrots and putting carrots, frozen carrots, even, in pies. And they were relatively easier to grow. And so there was sort of this -- for lack of a better term -- a propaganda type of effort to increase the amount of carrot production and consumption. And so that translated into this myth of getting ultra vision from carrots.

But in reality, carrots produce beta carotene, and beta carotene is a provitamin carotenoid, basically a molecule that needs to be converted to vitamin A that our body can use. The bio availability, as the term is called, or the ability to do that conversion, actually lowers the more that you eat. And so you can eat as much as you want, but it's not going to help produce any more visual success for your eye. So as long as you're getting enough of the daily recommended allotment of vitamin A, and you have been doing that for a while, and you have no issues with your gastrointestinal tract that you're aware of, over time, you should be more than fine with a few carrots a day and not overthinking it too much.

Host Amber Smith: You've been listening to ophthalmologist Dr. Mark Breazzano from Upstate Medical University.

And now, Deirdre Neilen, editor of Upstate's Medical University's literary and visual arts journal, The Healing Muse, with this week's selection.

Deirdre Neilen, PhD: Harmony Button has had her work published in "Best American Notable Essays of 2015." She gifted us with a gorgeous short poem celebrating the birth of a new family. Here is "Rich":

King-size sheets on a queen-size bed.

Corn silk scalp and milky head.

Late night night light salt lamp glow.

Daytime naps and days of slow

walks and long talks and rich snacks

in bed: Honeycrisp apples and almond-

dappled crumbs of toast we offer the dog

as we count and log the minutes of sleep and

ounces of milk. This is how we show our

love from before and our love's new debut:

clean sheets, warm sleep, a precious few

moments of skin on skin with not baby -- him,

my new old body back to thin and fits

against his torso for so long as we can until

our mouths that clutch unlatch

from one and open to another

as if the world were made of milk

and we three were, all of us, afloat

and drowning in it.

Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York.

Next week on "HealthLink on Air," how social workers are helping to break the cycle of street violence.

If you missed any of today's show, or for more information on a variety of health, science and medical topics, visit our website at healthlinkonair.org. Upstate's "HealthLink on Air" is produced by Jim Howe, with sound engineering by Bill Broeckel. This is your host, Amber Smith, thanking you for listening.