New Research into Chronic Tendon Pain

: On today's episode, new research into chronic tendon pain. Welcome to the podcast that gives you the most up to date, evidence based information on PHT rehab. My name is Brodie. I am an online physio, but I've also managed to overcome my own battle with PHT in the past. And now I've made it my mission to give you all the resources you need to overcome this condition yourself. So with that, let's dive into today's episode. Welcome back everyone. We have some new insights into chronic tendon pain, some new research, new papers I've just come across in the last couple of weeks. Luckily, the lead author was grateful enough to send me the PDF. And so I could start scouring through it. It seems very interesting. The title of the paper is, is chronic pain caused by neuropathy? Exciting breakthroughs may direct potential treatment. And so, uh, you know, usually when it comes to chronic tendon pain or just tendon pain in general, we seem to think that there's a lot of pain medias that go on from overuse. Um, sometimes from degenerative portions, you know, a lot of clients ask me like, what is actually happening? Why is my tendon sore? If it is strong, if I'm load managing it well, if it's been going on for a long time, like if there's no, you know, if there's no swelling. where's the pain actually coming from? It's very hard to uncover. A lot of people like don't know, it's very hard to pinpoint. And there's a lot of mechanisms going on. And so it's very hard for me to answer to the best of my ability. Or how I try to explain it is that there's some degenerative portions of attendant, particularly if it's gone through several months of mismanagement or poor load management, it starts to disorganize itself in a way. We've learned at uni that the tendon, if it starts to go through a chronic state of disorganization or, you know, disease, we could say, what we usually resort as a tendinopathy or tendinosis, tendinitis, you know, all those terms get thrown around, tends to increase its amount of blood vessels that get in there. Also the fibers themselves of the tendon become, you know, disorganized, they start to become a little bit more jumbled a little bit more. Instead of like an organized tendon that is very stable, very long, thin bound. fibers that are very straight and very organized. You know, this other one, there's certain images of the fibers themselves starting to splay out and sort of wrapping around one another and becoming entwined and entangled, along with a lot more blood vessels and a lot more of that, what we then call degenerative portions of the tendon. The pain itself is a bit more perplexing than that, because I've spoken to researchers in the past who have said that you can have a very degenerative tendon yet have no pain. And you know, someone can go out and play sport in their 40s and rupture their Achilles. Unbeknownst to them, they've had, it's been very degenerative that Achilles tendon. And that's why it's prone to snapping. A healthy tendon doesn't snap, but yet they've had no prior warning or no pain prior to that. And so sometimes, or some researchers I've spoken to have suggested that maybe the pain is from the healthy portions of the tendon that surround the degenerative portion of the tendon, which undergoes some sort of reaction, some sort of chemicals going on some sort of upregulation of pain mediators that then lead to pain. Very complex stuff. Anyway, that was sort of my prior knowledge until reading this paper. And I will admit it does get a little bit. complex. It's some sections of this paper actually go over my head talking about all the pain mediators, but I've tried to take my best snapshot of this paper and sort of boil it down into ways that I understand then hopefully ways that you understand. And then what if there are any exciting breakthroughs and things you need to know. So like I say, the title of the paper was is chronic tendon pain caused by neuropathy? Now what is neuropathy? I, as I'm leaning into more and more these days, asked chat GBT about how would I explain neuropathy. And it came back with neuropathy is a condition where the nerves in the body get damaged. Imagine your nerves are like electrical wires that carry signals between the brain and the rest of the body. These signals help to feel things, move your muscles and keep everything working properly. when someone has neuropathy, it's like those wires are frayed or broken. This can cause strange sensations like tingling, numbness or pain. And it can also make it harder to move or control parts of the body. It's a bit like having a faulty connection in a machine where these messages aren't getting through clearly or at all. So the nerves themselves are becoming dysfunctional. And maybe this is the source of the pain. Maybe it's not much to do with inflammation, not much to do with disorganization or overload. Maybe that might, you know, be some underlying causes, but the pain itself might be from these dysfunctional nerves, we could call it. And that's what the pain, oh, that's what the paper explores anyway. So I want to go through this paper, starting with the introduction, we can call it. sets up the stage quite well. It says that a tendinopathy accounts for 30 to 50% of sporting injuries and around 30% of musculoskeletal pain consults in the general practice setting, leading to a significant impact in quality of life and economic burden on the healthcare system worldwide. Classically, pain associated with tendinopathy has been divided as, has been defined as a collagen-related degenerative inflammatory disorder. fancy terms there. So collagen related, I guess, the collagen fibers of the tendon. Degenerative inflammatory disorder. So there's some sort of degeneration causing some sort of inflammation leading to the disorder. While degenerative and neo vascularization, that's the blood vessels that I was talking about and the degeneration being the fibers becoming disorganized. While degeneration and neo vascularization, have been historically associated with tendon pain, recent translational research has shown that chronic tendon pain may be primarily characterized by pathological nerve sprouting and neuronal ingrowth from the tendon envelope into the tendon proper. This is where, like in the paper itself, there's a whole bunch of, there's an image about all the layers of the tendon itself, but... They're talking about nerve sprouting and neuronal ingrowth, meaning like the nerves seem to be, the nerves can be sprouting, like growing new nerves and sprouting into different layers of the tendon. Cause I have an image in front of me, the tendon itself has several, several layers, like an onion, the big layer on the outside is your parotinon. And this is one that usually creates the envelope tendon, it houses everything else within it, it contains a lot of the nerve and blood vessel supply. But then everything else that gets lower and lower and lower all these layers of the onion don't really have much nerve innovation don't really have much blood vessels in them. But you know, as we go deeper and deeper and deeper. As we get into the pathology, it seems like these nerves are not only sprouting and growing new nerves, but it seems like they're somewhat penetrating the envelope and getting deeper and deeper into these layers. The paper continues, these have been hypothesized to cause receptor signal with evidence supporting their involvement in chronic tendon pain. These findings suggest that the biology of tendon pain is more intricate than previously understood. Now, as they go through all of these hypotheses that sort of stuff. If you're familiar with any papers, they sort of create little references. And when it talked about pain mediators, and this potential hypothesis of nerve sprouting, and neuronal in growth, they do leave some references. So I actually went and checked out those references. And I found a paper, let me go find it. The title of the paper was is neurogenic inflammation involved in tendinopathy a systematic review. So just in tendinopathy clients is the inflammation of the nerves or the sensitivity of the nerves driving this pathology. And so I got a bit of a summary here what the paper found. Like I say, it was a systematic review. So collecting a whole bunch of previous papers about this subject and trying to correlate it and come up with something, a bit of a consensus. is associated in tendinopathies. They say that the study reviewed evidence showing that a specific type of inflammation called neurogenic inflammation is involved in chronic tendon injuries. This means the nerves of the tendon may play a greater role in causing pain and inflammation than previously thought. Markers of nerve activity. Researchers found that certain markers associated with nerve activity were more active in tendon and injured tendons compared to healthy ones. This suggests that the nervous system is actively contributing to the problem in chronic tendon injuries. They talk about the sympathetic nervous system and its involvement. So the sympathetic is like your fight or flight response. It's the parasympathetic, which is the opposite, is your rest, digest, relaxation type of thing. And so they said that... The study also highlighted the involvement of the sympathetic nervous system in tendinopathy. Markers linked to this system were found to be upregulated, which could be contributing to the persistence of pain and difficulty in healing. So those who have an upregulated sympathetic nervous system, which might be stress, which might be decreased sleep, which might be general inflammatory markers, can lead to persistent pain and difficulty healing. Why this is important. we need to, when it comes to understanding pain, if nerves and neurogenic inflammation are key players in tendinopathy, treatments can target the specific pathways, which might be more effective at reducing pain and promoting healing in people with chronic tendon problems. So starting to emerge like, we're not just talking about getting the tendon stronger. We're not just talking about activity modification. We're now talking about involvements of the nerves, reducing your sympathetic nervous system, reducing some factors that might correlate to neurogenic inflammation, inflammation of the nerves or yet the primary role of the nerves, which I'll get to shortly, but more and more papers that I'm uncovering are starting to find these associations and sort of link this whole breakthrough. So back to the previous paper. They continue by saying, in a healthy tendon, the innervation of tendons originates from the surrounding cutaneous and deep peritendinous nerve trunks. The nerve fibers cross from the myotendinous junction and penetrate through the endotendon, endotenon septa. I don't know why I include that and highlighted that. It's very complicated, but essentially meaning that they originate in sort of the outer layers and they sort of penetrate into the endotenone, which is 123, the third layer in this onion. So we're not down into the collagen fibers yet. It's they do go a little bit deeper. That's, I guess that's sort of how far the nerves seep into. They say the innovation is mainly found in the tendon chiefs, which is like the outer layer, I guess only a few break and penetrate that far down. but tendon homeostasis is maintained by the tendon envelope. This is like the outer layer that I was describing. This histological finding implies that the tendon envelope is the major regulator of tendon pain, kind of like a gateway, kind of like a, I don't know, wrapped around in some sort of protective layer. In chronically pathologic tendons, excessive and protracted sensory nerve sprouting in the tendon proper has been identified. This robust inward direction Neurogenesis has been associated with the release of pain mediators such as substance P and glutamate. I told you that there's a lot of complexity to this study. But this level of physiology isn't really my forte. But essentially, what they're saying is, it seems like, as I highlighted before, in chronically, in the pathology of the tendon pain, if it becomes more prolonged, there seems to be more sensory nerve sprouting and seems to be, I guess, penetrating deeper and having with that a lot of a lot more pain mediators being released. And this got me on the, they mentioned the glutamate and they mentioned substance P. I don't know much about that. So I went digging again, they referenced more papers here. They said that substance P and glutamate were believed to play a significant role in the immune system and peripheral nerve ending activation via certain receptors. And so I'm like, okay, well, how significant is this substance P? Because it goes on to say, moreover substance P may stimulate peripheral nerves and lead to neurogenic inflammation. So one of these mediators is believed to be Once there are more sprouting of the nerves, we now have this substance that is now making all of those nerves more sensitive, it seems to be, or, you know, leading to pain and inflammation in that particular site. They say the activation of neuroimmune pathways and neurogenic inflammation can contribute to developing and maintaining chronic tendon pain. So it seems like this substance P is very important. And so, I went digging a bit further and I found a second paper, which was titled, Sustained Exposure of Substance P Causes Tendinopathy. That's the title of the paper. And they found several things along with ways we can kind of help. So I thought I'd go through those. First of all, they said, when it comes to substance P and tendinopathy, they say that the study found that long-term exposure of a molecule called substance P can lead to tendinopathy, a condition where tendons become painful, inflamed and weakened. Substance P is a neuropeptide, which means it's a small protein-like molecule involved in the communication between nerves. And I guess in the presence of this leads to a lot of inflammation and a lot of pain. They say when it comes to the tendon cell changes, when tendon cells are exposed to substance P over time, they show increased proliferation. However, this came with the downside. The cells started producing more immature and disorganized collagen, which weakens the tendon structure. So obviously long-term exposure to the substance P not only contributes to pain, inflammation, but also disorganization of those collagen fibers. Continuous exposure to substance P led to increased inflammation in tendon cells. This was indicated by a significant rise in the marker called IL-6, which is linked to inflammation. Inflammation can further contribute to tendon damage and pain. So then I asked the question, how is someone exposed to substance P over long periods of time? I asked Chet GBD as I am sort of gravitating towards these days. So long-term exposure to elevated levels of substance P can occur in various ways. Number one, chronic stress. Prolonged psychological or physical stress can lead to increased levels of substance P in the body. Stressful conditions cause the body to release substance P as part of the stress response, contributing to inflammation and pain, particularly in the muscles and tendons. So chronic stress. I think we've done some pain science episodes in the past linking. chronic stress to chronic pain, linking to, you know, recovery of long term chronic pain by helping and assisting with chronic stress. And so now we're sort of coming up with down on the biological level why these connections are at play. So chronic stress was number one. Number two was just persistent inflammation conditions that cause chronic inflammation such as autoimmune diseases, rheumatoid arthritis. or chronic infections can also lead to this high level of substance P. Number three would be repetitive strain injuries. If you're constantly causing micro injuries to the body and not getting adequate recovery, this can also be a link. The next one was diet and lifestyle. Some research suggests that a diet high in processed foods, sugars and unhealthy fats may promote inflammation and stress in the body. indirectly leading to higher levels of substance P. Additionally, lack of sleep, poor mental health, and a sedentary lifestyle can contribute to chronic stress and inflammation, elevating substance P levels. This is like, well, I'll get to the last one. The last one they say is environmental exposures. Continuous exposure to environmental toxins, such as pollution or chemicals, can cause low grade, chronic low grade inflammation in the body. which might lead to increased substance P production over time. So like I say, this is not just about strengthening the tendon and load modifications, we're now looking at lifestyle modifications to help down regulate substance P so that you are in a healthier state, an inflammatory state for healing. Okay, let's go back to the original paper. because now it starts to talk about treatment, which doesn't sound like there's not a lot of evidence behind it, but they are running on certain hypotheses and based on these, or what their current findings are, these may have potential treatment benefits. But I was almost thinking, do I keep this in because I know a lot of you are listening will look at these treatments and be like, this is the answer and go search for it. Which is why I sort of started off with those environmental changes that you can make to down regulate substance pay if you feel like this is resonating with you. A lot of those changes you can make yourself through diet, lifestyle changes, stress management, all those sorts of things. Instead of being quite fearful that these next upcoming procedures that I'm about to suggest are the only cause, well, you know. them. These are only potential there's not a lot of evidence to support their use, but don't want people to be too fearful either. I'm being like, this is the only way I can negotiate this chronic tendon pain. So bear that in mind. I was thinking maybe don't include it because it's going to enlist it a lot of like worry, anxiety and fear and those sorts of things. But I feel like I'm doing you and I guess myself a disservice if I ignore the, what the paper is continuing with just because I feel like it's going to be anxiety provoking. But nonetheless, I feel like I deserve and you deserve me to include this. So we continue. It says the identification of a neural mechanism in chronic pain rises a possibility of developing a procedure to disrupt neural outflow. So if it's a neural issue, a lot of these nerves are being formed. and they're being very sensitive. This is how, this is the direction of treatment that maybe should be taken. They say we believe the treatment can target pathologic parotenon nerves and should be expanded and explored in greater detail. Some studies have demonstrated that disrupting unmyelinated sensory nerve propagation in intertendons have demonstrated pain improvement. I didn't know what that meant. So they had one reference and It was leading to a paper that said, the title of the paper was shockwave therapy, shockwave application to the distal femur of rabbits diminishes the number of neurons immuno reactive for substance P in dorsal root ganglia L5. Crazy. But it seems like some shockwave application to rabbits reduced the amount of substance P in the body. think. I couldn't find that complete paper, but just going off the title. They continue to say furthermore, the surgical techniques aim to disrupt the pathological nerve in growth by denovate the origin through loosening or releasing the parotinone from the fibrous tendon proper, and as believed to be a crucial role in alleviating pain. Seems like there's some sort of what they've called surgical technique to remove or detach or separate the nerve from the parotinon. Didn't know much about that, but that's what they said. They then talk about radio frequency ablation and says it may be one method of denovating structural compromise of the tendon itself. So this radio frequency ablation may be an option. They then say that injectable medication may be an option for treatment, but identifying or creating a substance which will selectively affect immature neural tissue without disrupting the integrity of the tendon may be challenging. So if you inject something, it's very hard to dissociate between what they want to improve and what they don't want to improve, that might influence the healthy parts of the tendon, vice versa, all that sort of stuff. The use of ultrasound guidance in the percutaneous ultrasound guided tenotomy, also with the abbreviation of PUT, also enables accurate real-time targeting of the diseased tendons, leading to precise treatment. and minimizing the risk of damage to surrounding healthy tissue. So if you're interested in learning more about percutaneous ultrasound guided tononomy, you can look that up. I have had some people undergo this with various success, but you know, that's why we need to be very careful about selecting these sort of things. They also mentioned the Tenex, 10X device. and say this is a novel therapy, which involves the application of a specialized dual chambered needle that derives high frequency sound waves to fenestrate the parotenone and the affected tendon. These high frequency ultrasound waves create micro vibrations that induce tissue separation. This fenestration of the parotenone, the major regulator of pain, could potentially induce separation of the tendon proper from their source of pain and contribute to denervation itself by disrupting nerve ingrowth. Classically the PUT primary targets the which was the I'll say it again the precutaneous ultrasound guided tonotomy. It was primarily targets the pathological tendon and is thought to promote tissue healing and regeneration. However, the rapid improvement seen in many patients may argue against this mechanism, meaning that people are seeing improvements too quickly for that to be a potential. Okay. Denervation of the parotinone by PUT, induced demyelination might be an intriguing explanation for PUT related relief. Histoanalysis may confirm our supposition and encourage more widespread application of PUT for the treatment of chronic tendon pain. End paper. That was a bit of a ride and I struggled to get through. I'll be honest. But the lead author of this paper is, like I say, they sent me the PDF, which was great. And they said that they are releasing two more papers in the next six months. And I'll love to get them on the podcast to have a deeper chat and maybe answer some of your questions along the way. Um, but new insights. I didn't learn this at uni. Uh, I haven't really dealt much into this yet, but I have some key takeaways here. Um, like I say, this was complex. This was a lot of this went over my head. Um, tried my best to, you know, disseminate a lot of the jargon, but sometimes unavoidable at this stage, but key takeaways, um, what I think, uh, the novel understanding of these pain mechanisms. I think one of the main takeaways which I found in this paper was the paper highlights the chronic tendon pain might be primarily neuropathic caused by a pathological nerve sprouting and neural ingrowth rather than just being a degenerative inflammatory disorder. This new understanding opens the door to more targeted and potentially more effective treatments. I think this can be reassuring in a way because a lot of people when they are in pain and they do their treatments, they're not seeing a lot of improvements yet. They feel like they're doing more damage, they feel like there's a tear that has to be corrected, they feel like they need surgery because they're not getting any better. But I would say in a lot of ways, this is reassuring to know that look, just because there's pain in a chronic tendon, tendinopathy, doesn't mean you're doing more damage, doesn't mean you're doing like a disservice, doesn't mean... it's not effective, it just means that the nerves themselves are more sensitive than usual, and we need to explore like a bit more of a holistic approach at decreasing this substance P, decreasing the inflammation, inflammatory state, and trying to settle things down. Hopefully you find that same reassurance. Some other takeaways that I found in these papers, the monitor. how to monitor and manage the inflammation. So reducing inflammation is essentially like helpful in managing this tendinopathy. Anti-inflammatory treatments, whether through medication, physical therapy or dietary changes, might help mitigate the effects of substance P and other inflammatory agents to your tendons. The emerging treatments, like I said before, this percutaneous ultrasound guided tonotomy is just high frequency sound waves and is a intervention. that shows promising stuff for targeting the neuropathic components of the chronic tendon pain. These treatments focus on disrupting the pathological nerve pathways and could lead to significant pain relief. Potential for pain relief as well, disrupting the nerve ingrowth and neural outflow, which are now believed to be the central, now believed to be central to chronic tendon pain may offer substantial pain relief. This is This is a promising development for those who have not found relief through traditional treatments. I'll keep you guys updated. Like I say, there's more papers that are due to come out in this particular topic. Maybe this has helped create some relevance or some tangible connections to decreasing or actively doing something to reduce your amount of stress, that being like physical stress or psychological stress. Maybe that's helping explore some inflammatory diets. I've spoken to Rowena Field in the past who's doing research on anti-inflammatory diets and chronic pain relief. I've done some interviews with her on the Run Smarter podcast before and she said she's had people with years of plantar fasciitis go on a low or an anti-inflammatory diet that usually being low carb. But seeing success, all of a sudden they're having less pain, pain that's hasn't been that low in years, just with the change of diet. And so starting to see some connections there. And maybe after listening to this episode and recognizing those connections, it might help make it more real and help maybe see, take different approaches on top of the load management, getting stronger, building up stronger tendons, safe load management, maybe some of these things. diet, lifestyle, environmental changes might just help bring all that change. Like I say, I'll keep you updated. I keep my finger on the pulse when it comes to these research papers and I do have the contact email of the lead author now. So we'll be in close contact and hopefully we can start uncovering more. And as I'm learning, you're learning as well. And I hope you enjoyed. Something like this, like I say, it is a bit more scientific and a little bit more technical, but hopefully you found it useful. If you are looking for more PhD resources, then check out my website link in the show notes. There, you will find my free PhD five-day course, other online content, and ways you can personally connect with me, including a free 20-minute injury chat to discuss your current rehab and any tweaks you might need to make. Well done for taking an active role in your rehab by listening to content like this. together we can start ticking off all of your rehab goals and finally overcome your PHT.