Pain Medication and Exercise: How Analgesic Medications Impair Healthy Muscle Function With Bahar Shahidi PT, DPT, PhD

Welcome back to the Healing Pain Podcast with Bahar Shahidi

We’re talking about analgesic medications and how they can have both a positive and a negative impact on how your muscles function. Analgesic medications are simply medicines that are used to alleviate pain. You may have seen them marketed as painkillers or pain relievers. Technically the term analgesic refers to any medication that provides pain relief without putting you to sleep or causing you to lose consciousness. There are many different types of medications that have pain, relieving properties. Some people tend to lump these all together, but they’re different groups or types of medications.

Some common names you might have heard of are non-steroidal anti-inflammatory medications, such as NSAIDs. These include things like Aleve and Advil. Another group is narcotic opioids, like oxycodone and morphine, and then another common group or non-opioid analgesics typically falls into that category are things like acetaminophen or Tylenol. In many cases, the effect of treatment of chronic pain may include one or more of the analgesic medications I previously mentioned.

However, the use of analgesic medications can be potentially challenging for physical therapists because they’re faced with a paradox. On the one hand, an analgesic medication may alleviate pain, which you may think makes it easier for people to move and function. Yet, on the other hand, these medications may negatively impact the physiology of your muscles, nervous system and other parts of your body. Here to talk to us about analgesic medication is Dr. Bahar Shahidi.

Bahar is a physical therapist and a researcher investigating how analgesics impact muscle physiology, pain as well as physical function. She is an assistant professor in the Department of Orthopedic Surgery at the University of California at San Diego. Her academic background includes a Bachelor’s in Chemistry, a Doctorate Degree in Physical Therapy and a PhD in Neurophysiology. Her research focuses on muscle physiology changes in the presence of chronic spinal pain.

In this episode, we discuss how analgesic medications impact clinical outcomes in people with chronic low back pain, exercise responsiveness, how to time the use of analgesic medication relative to physical therapy treatment, and balance medication use and exercise for optimizing patient outcomes. Let’s begin and meet Dr. Bahar Shahidi and learn about how analgesics impact muscle physiology.

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Pain Medication and Exercise: How Analgesic Medications Impair Healthy Muscle Function With Bahar Shahidi PT, DPT, PhD

Bahar, thanks for joining me on the show.

Thanks for having me.

You published a paper in the 2021 PTJ, the Journal of Physical Therapy and Rehabilitation. The title is Analgesic Medication Use During Exercise-Based Rehabilitation in Individuals With Low Back Pain: A Call to Action. I said, “If someone’s got a call to action, then we’re going to talk about it on the show.” Thanks so much for joining us. Talking about analgesic use during exercise, which is what we do as physical therapists primarily. You have some good data on it. There are also some gaping holes in the literature too.

There are more gaping holes than there is information, particularly in people who have any type of pathology, and that’s with or without pain. I think one of the main points that we wanted to bring up is that a lot of the data that’s out there on analgesic use is done in healthy people. Interestingly enough, because you would think that more information exists on analgesic use and people that have pain or some chronic pathology, particularly in the context of exercise.

HPP 240 | Analgesic Medications
Sometimes people already have expectations that a passive modality will work better for them than an active modality. These things influence the success of your outcomes when in conjunction with each other.

 

There is not a lot of information on how analgesic medications influence an exercise protocol and what you’re trying to accomplish with exercise-based rehabilitation. The call to action was to try to highlight and bring to the forefront this big issue that we, as physical therapists, are constantly trying to balance what we’re trying to do in terms of improving someone’s physiology, recovery, muscle stabilization and activation but we’re trying to battle with pain at the same time. What are tools that we can use to accomplish that? We probably need to know a little bit more about how those things interact.

It’s a great place to start. Obviously, there is a place for pharmacologic pain management and rehabilitation because sometimes things tend to swing away. Opioids were hot and still are, unfortunately, in certain populations and then things swing over to absolutely no opioids, but there’s a place for pharmacologic management here.

I think it’s important to recognize pharmacological management. A lot of people think of that as focusing on opioids as a primary group. That is probably fair in chronic pain populations. That’s certainly has a very high opioid use population. That’s oftentimes a group that we as PTC. I also think that some of the more over-the-counter, regular run-of-the-mill analgesics Tylenol, NSAIDs, ibuprofen, Motrin, Advil, all of those things we tend to think are regular, okay analgesics to use, but there are some implications for their use in what you can expect to see in exercise-based rehabilitation. Those also need to be considered and not ignored as a standard of care because right now, they are standard of care, and most patients will take them as needed. In addition to the opioids, that’s something that we probably need to pay a little bit more attention too as well.

What do we know about analgesics as far as having a positive or any impact or outcome on low back pain?

I think that if you look at the clinical guidelines from pharmacological management, which most people would argue even before PT, with this PT1st Movement where we’re trying to get people into physical therapy as early as possible. People are still getting pharmacological management before they’re getting PT in most cases. The data on the effectiveness of different analgesics in isolation before any other treatment is implemented poor in terms of efficacy.

The clinical practice guidelines for pharmacological management of low back pain are all over the board across the world. There’s a lot of geographic variabilities. In the United States, it used to be that Tylenol was the number one recommendation for the first line of action for pharmacological management. Now that’s swinging a little bit more towards NSAIDs, particularly in other countries, Australia, Europe, etc. Interestingly in the US, we’re the only ones that are teeter-tottering between a combination of muscle relaxants and NSAIDs. There isn’t a lot of data to support, which is confusing.

The point there being people don’t know what to do, and that’s probably why we see primary care shifting a little bit more towards opioid prescription. There isn’t a great consistency or efficacy in the first-line management recommendations across the world for what we’re supposed to do and what we’re supposed to prescribe. The efficacy is low, the variability is high, and there is absolutely no data on the combined efficacy of analgesic medications and rehabilitation. It just doesn’t exist. Pharmacological management and isolation, and then there’s rehabilitation and isolation, and there’s no crossover or data that implements or pays attention to both those things as an interaction. That’s a huge gap in the information, the literature, or in the way people are even thinking about the problem at the moment.

It’s not new, right?

Absolutely. For decades we’ve been working together with pharmacological management. It’s integrated into a patient’s care. We oftentimes pay attention when we ask, but we don’t document it either. As a pattern, I don’t think and observe that many people will document routine analgesic use unless there’s a concern of high opioid use and that is a separate risk factor for other things. PT will ask the question like, “Did you take your medication before you come? What’s your pain level?” As part of this whole pain as a vital sign type of question, people will ask, but they never document it.

HPP 240 | Analgesic Medications
The different classes of analgesics have different differential impacts on muscle growth.

 

That has left us with a little bit of a gap in even pattern generation as part of the anecdotal practice. You build these patterns as part of practice based on your observations, but if you don’t document it, you’re not paying attention to what those patterns could tell you over time. That’s part of a call to action, as well. These are things that we have in our back pocket and we oftentimes do ask the question, but we need to be more intentional about paying attention to what those answers lead to.

In your paper, there’s this great image like four squares and one square is on the regenerative capacity of the body or the musculoskeletal systems on the motor drive. One is on exercise tolerance and one is on force production. You’re starting to say, “Here are the areas that we should be aware of with regard to improve function.” Let’s start first with regenerative capacity and protein synthesis. We’re going to go through these one-by-one. How’s that impacted by analgesics?

The different classes of analgesics have differential impacts on muscle growth. The fundamental foundation of muscle growth is protein synthesis. If you look NSAIDs, which are one of the most commonly used analgesics in PT or during PT, you would think, again, no data, the use of NSAIDs has been shown to reduce protein synthesis in response to exercise. This is in healthy individuals. A lot of the science has been done in healthy people, not people that have muscle pathology, pain, or other types of issues, so we’re making some assumptions here.

In healthy people, NSAIDs reduce the protein synthesis capacity and muscle hypertrophy that results from that by up to 50%. That’s a big influence on your capacity for the muscle to adapt. Muscle hypertrophy is not the only goal. There’s a lot of neuromuscular re-education that’s happening, and that’s totally fair. If your goal is to improve stabilization in part due to muscle hypertrophy and somebody is concurrently taking NSAIDs, you can assume that their protein production and ability to mount that hypertrophic muscle response is going to be severely inhibited.

It also impacts endurance through reduced mitochondrial function, so it affects the mitochondrial machinery. It reduces its capacity to function and that’s through that cycle oxygenase mechanism. Finally, it reduces the muscle stem cell capacity to differentiate. Satellite cells are responsible for muscle cell differentiation. If you don’t have that or if that’s inhibited, then you’re not going to make the cells that you are trying to make in response to exercise and exercise-induced muscle damage, which is the stimulating factor for muscle growth.

These three factors, the protein synthesis, the mitochondrial machinery, and the impaired satellite cell activation and differentiation, are three areas where NSAIDs, in particular, are known in healthy muscle to impair muscle growth. The issue here is that nobody’s done these experiments in people that have pathological muscle or pain. The ability for someone without pain or pathology to mount a response is much different, particularly if they’re not limited by the amount of pain.

That’s the balance point because we’re trying to battle this other influencing factor. We’re trying to battle the fact that somebody might not be able to reach the levels of force production that they need to elicit a hypertrophic muscle response or get that physiological adaptation stimulus. If we can’t get them there, then they’re never going to adapt anyway. We want them to be on analgesics to help them get to that level of force that they need to be this induced physiological adaptation.

Once they reached that, they’re going to be inhibited anyway. It’s a little bit of a Catch-22. We probably need more information on what the balance point is there, or maybe there’s a different combination of analgesic medications that don’t have that same inhibitory influence. Tylenol is a great example. It doesn’t have the same inhibitory effects as NSAIDs do or at least it doesn’t do that at the same magnitude, but it also doesn’t provide the same level of analgesic effect.

Opioids, on the other hand, don’t have an effect or inhibition on those peripheral muscle adaptation components, but they do affect you cortically. They are central nervous system depressants. They’re reducing your ability to hype- up your motor drive, which is already inhabited by pain. People don’t want to use as much force during their exercises because they’re inhibited by pain. Opioids then further inhibit because of their central nervous system depression type mechanism.

Opioids don’t impact muscle cell physiology the same way NSAIDs do, although it’s interesting though, long-term opioid use has been implicated in hormonal changes, both male and female hormones. I would imagine somewhere down that pathway, and as you mentioned, all this needs to be investigated further, but there’s probably some implication there for long-term muscle physiology, but a different pathway potentially.

We don’t know what the direct influences are there.

At the NSAID part, as you’re talking, I’m getting these flashes of post-operative patients who are extremely atrophied after surgery, specifically a total knee replacement. Athletes who injured themselves and oftentimes, they turn to NSAIDs as the first line of treatment. That’s a population that we’re extremely interested in maintaining the normal regenerative capacity so that they can function and be in a sport. You mentioned exercise tolerance. Are there medications that help with exercise tolerance that were beneficial for physical rehabilitation?

I don’t think that there’s data that supports that. There isn’t any information about the interaction between analgesic medications in the context of exercise-based rehabilitation. The best data that’s out there is probably associated with the elite athletic population. As part of this whole sports performance push, they’re trying to mitigate any of the negative influences of their overused in many situations. It’s not necessarily that they have pathology or pain. They’re highly functional and constantly pushing their physiology.

That’s probably the best place to look at data about analgesics in that context. The data there is that kind of leads a little bit towards the concept of timing of medication use, not necessarily which ones you’re using, but when you’re using them. I think most athletes are a little bit narrower in what analgesic medications they’re taking. Most athletes take NSAIDs in that type of scenario. The timing of medication relative to NSAIDs is important.

HPP 240 | Analgesic Medications
The three factors – the protein synthesis, the mitochondrial machinery and the impaired satellite cell activation and differentiation – are known to impair muscle growth.

 

Again, very little information here to go off of, but the information we do have about timing is if you take the NSAID before you start exercising, you are subject to those protein, mitochondrial, and satellite cell differentiation, inhibition processes. If you take it after you exercise, those same processes don’t seem to be present but it also doesn’t do its job of preventing delayed onset muscle soreness or providing you with the analgesic effect you’re looking at.

If you take it before, then it works better in terms of the actual analgesic effect. If you take it after, you’re not using it for what you wanted to use in any way in terms of the analgesic component. I don’t think that there’s a great solution other than not using an NSAID and potentially trying to go more for something that doesn’t have as large of a magnitude of that inhibitory effect as Tylenol.

Although I do think what you said might be a good piece of information for informed consent when people decide, “Here’s my personal choice on how I choose to use this medication either. I’m going to take it before I exercise or after exercise. I’m aware of what the potential side effects might be for my athletic performance and body, basically.” I’ve never heard any professional talk about that.

I don’t think people think like that. They may think like that more in the world of athletics and performance because they’re trying for that top 5% of optimization. I think of general physical therapists unless they’re working with that population if you’re dealing with low back and chronic pain, you’re not even there. You’re not even looking at the top 5% for optimization. You’re looking at any type of effect or leg-up that will help your patient tolerate what you need to do in order to gain them the stability, improved function, activities of daily living, and even the confidence to participate in the levels of activity that are going to be beneficial for them to manage their condition.

Do some of that apply to how we would approach us in our treatment sessions as well as physical therapists? Are the same principles apply there?

I think so. It’s going to take us a while to get there but I would imagine the way that we would use this information in practice is, number one, just like we normally do with any type of patient. You look at where they are on the spectrum of function and what your goals are in terms of how active and how much performance-based you’re looking at there? How complex is that patient? Based on that, you’re providing them the education and information about the impact of the medications that they’re taking or their options for medications are.

It’s not within our scope of practice to be able to try to recommend specific medications and how much, but we probably can give them some information on timing. I think that’s definitely something that we can impact. We can give them some education on what the different types of medication can do so that they’re more informed. They can ask in conjunction with their providers, pharmacologists and whoever else is involved in their management. You can work together to try to bring these issues to the forefront so that they’re like, “This isn’t for my pain. This is also for my function.” I’m trying to triangulate all of these things together with the patient to make sure that they are empowered to have those discussions with the people that can help manage them.

That brings me back many years when I first worked in a hospital in-patient rehabilitation and back then, many of the patients had patient-controlled analgesia so they can push their own button, which would give them a small dose of some type of opioid. Many of us, as PTs, were encouraged like before you ambulate the patient before they get out of bed, encourage them to press that button basically. As I see some of this information here, not only was I probably upon in some opioid game that was happening way back when.

I also look at this, and I’m like, “If I had this little diagram you have in your paper if I had this in front of me, I might be able to help make a better decision for myself and the patient with regard to what they particularly need.” If I notice someone has having regenerative capacity, then I could say, “Doctor, you prescribed NSAID for this person. I think this person might be better on Tylenol.” This is important information for the physician as well.

If you think about it, the physicians already use this information in different types of settings. I’m going to use the world of the spine because that’s the world that I spend the most time in postoperative spinal fusions. They’re not prescribing NSAIDs because they know it affects bone healing if you think it affects bone healing and don’t think it affects any of the other tissues, and that’s a very myopic view. These guys know and are familiar with that concept, but they are not used to applying it to other tissues. They’re bone guys. They’re putting bones back together and focused on their hammer and nail. Our focus is on a different set of hammers and nails. If we thought about it from a broader perspective, NSAID is a broad anti-inflammatory and affecting multiple tissues in multiple systems.

It makes sense to think that if you’re influencing regeneration capacity in one tissue, you should be influencing regeneration capacity and the other, and the expectation that they’re going to send the patient post-op to you. You’re going to be able to regenerate their muscle when they’re not allowed to take an NSAID because their bone needs to regenerate. Some of those things end up working together because of the post-op protocols there. Those guys think about it relative to a different tissue type.

Have people reached out to you with regards to this call to action and said, “It has been interesting and great information.” I know you have probably some works that you’re going to roll out in the future around this topic.

HPP 240 | Analgesic Medications
The ability for someone without pain or pathology to mount a response is much different, particularly if the amount of pain does not limit them.

 

This call to action was like the opening volley for a five-year NIH-funded project that is trying to fill some of these data gaps that we bring up in the paper. One of those things being, “We don’t have any information on what the medication behaviors are for people once they are in an exercise-based rehabilitation program.” We know what they’re doing outside of that, but how does being involved in PT influence their medication, taking patterns, and what are the components that influence that?

It’s not just PT. It’s all of these other factors that we know also influence exercise, fear-avoidance behaviors, anxiety, depression, expectations and beliefs on what they think is going to be the most beneficial for them in the long-term whether they already have some expectation that a passive modality like medication is going to work better for them than an active modality like exercise. These are all things that influence the interaction and what your outcomes are going to be when those two things are working in conjunction with each other.

Collecting data on that is the first step. Once we understand what the profiles and influencing factors are, we can then be a little bit more intentional about paying attention to, if this person, in the absence of all of these other complicating factors, is taking their medication before or after. What is their influence on exercise performance? What is their influence on their ability for muscle hypertrophy in response to a longer 10, 12-week exercise resistance strengthening program? Those are the types of questions that we’re trying to answer after we have a little bit more of an understanding of what the profiles look like for patients that are taking medications in an exercise-based rehabilitation setting.

I’d imagine studying low back pain is probably the easiest to study. You typically have a lot of data around lower back pain or it’s easier to collect data around those groups. Although, as you’re talking, I’m looking at things like regenerative capacity and protein synthesis, I can’t help but think, “There are autoimmune diseases which are inflammatory processes. There’s active inflammation there.” You think you want to lower inflammation, but at the same time, we may be causing joint destruction to happen in those populations. There’s nutrition that comes in that has an impact on all the cellular mechanisms. Even if you’re not taking a medication that could be negatively impacted, you still have to have the proper nutrition to have all this strung along.

That’s another component. We have a separate clinical trial that’s looking in this patient population the addition of a protein supplement through the program. Analgesic medication is one thing but to make sure that their progress or lack thereof in terms of what is happening with their muscle physiology is not limited by lack of appropriate nutrition. We’re also in parallel looking at that as an intervention to see if we can mitigate potentially. Maybe that’s a combination we can look at.

You can take analgesic medications, but you also have to mitigate some of the inhibitory effects by supplementing with something like protein. It’s a reasonable concept, but we have to collect the data and see that project a little bit farther along to understand what the implications are going to be. Those are the types of things that we are looking at in the future to try to understand. We can pick and choose how to pair these things together to make sure that based on the patient’s goals and how far along they are in the spectrum of function and performance, we can get it right. This is the concept of applying precision medicine to physical therapy in some ways.

I love that precision medicine. That’s where we should be. We do know that protein needs to go up when people exercise, and essentially, every patient who’s coming to us, as a physical therapist, probably having increased protein needs. As you mentioned, that could be a branch-chain amino acid supplement or encouraging someone to increase their protein intake a little bit.

A little bit of nutrition education can potentially go a long way and that’s part of this potential conversation as well in terms of muscle adaptation and all of the things that are required to make that wheel go round, particularly in the context of aging too. Many of our patients are older. I’m going to, again, talk about this from the spine perspective but most people that have chronic low back pain are over 50. We know that at the very least over 60, there are significant reductions in protein synthesis, even in even the process of healthy aging in response to exercise. There’s some information about aging in the use of analgesic medication but there’s not a lot.

It does seem interestingly enough that in the aging population, the inhibitory effects of NSAIDs are not as profound. It could be because the aging population isn’t able to get to that threshold anyway so the analgesic medications don’t have that much influence. There are some groups that are looking specifically at aging and the impact of analgesic medications on the aging populations. It’s one more step to understand and one more variable to understand. This is a very complex problem like most of our patients.

It’s fascinating research and I’m looking forward to you releasing some more of it because it’s information that all of us physical therapists and other practitioners who work with people who have chronic pain. It’s vitally important information. Bahar, how can people follow you and learn more about your research as it rolls out?

I think the best place to follow me is on ResearchGate because I’m always updating the publications from this project on that platform. There’s a specific project line on ResearchGate that people can keep track of and any updates usually go in that place. You can find that under my name, Bahar Shahidi.

Make sure to bookmark Bahar Shahidi in ResearchGate. You can follow Bahar’s work as more information starts to roll out on how analgesic medication impacts exercise-based rehabilitation and not only individuals with low back pain, potentially others as we see more research. I want to thank Bahar for being on the show. Make sure to share this with your friends and colleagues who are interested in analgesic medication and exercise for rehab. Make sure to hop on to the Integrative Pain Science Institute and join the mailing list so each week I can send you the latest update, like this awesome episode with Bahar.

Thank you very much.

We’ll see you next episode.

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About Bahar Shahidi

HPP 240 | Analgesic MedicationsBahar Shahidi, PT, DPT, PhD is an assistant professor in the Department of Orthopaedic Surgery at University of California San Diego. Her academic background includes a B.S. in chemistry from UC Berkeley, a doctorate in physical therapy (DPT) from University of Colorado Denver, a PhD in neurophysiology from University of Colorado Denver, and a post-doctoral fellowship in skeletal muscle physiology at the University of California, San Diego. Her research background includes understanding biological, neurophysiological and psychosocial contributions to the development and maintenance of spine disorders with a focus on pain processing and motor control. Her current research focus is on muscle physiological changes in the presence of chronic spine pain. These projects apply biological, physiological, and imaging-based tools to understand the mechanisms and clinical implications of muscle degeneration, atrophy, and fatty infiltration of the spine musculature with the overarching goal of identifying successful patient-specific treatment strategies in individuals with degenerative spine conditions such as scoliosis and chronic low back pain. She is currently funded by the National Institutes of Health (R01-HD088437-01A1, R03-HD094598A, R21-109852A) and the Foundation for Physical Therapy Research (Magistro Family Award).

Dr. Shahidi also has 9 years of clinical experience as an outpatient orthopedic physical therapist specializing in chronic spine conditions. Additionally, she has extensive teaching experience both clinically and academically, serving as a primary instructor or assistant instructor for the Physical Therapy program at the University of Colorado Denver; Orthopaedic Surgery Resident program, School of Medicine, and School of Pharmacy at UCSD; and Physical Therapy program at San Diego State University.

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