So in this lecture, we're going to talk about chronic pain. But before we get to chronic pain, let's talk for a minute about acute pain. So acute pain everybody has experienced it, right? It's basically getting chopped down on the soccer field, getting kick in the shin, it's a stubbed toe, it's a slap in the face, maybe a sore throat from a cold or a virus, it's touching a hot pan. We've all experienced these things. When you touch a hot pan what happens is that there's a neural signal that's created when you touch the hot pan that travels up your spinal cord to your brain and creates the experience of pain. That signaling is very important because that signal of pain, basically your brain can then say okay, I have to move my hand or am going to get injured. So it's a protective mechanism that basically allows you to hopefully not get severely injured. So acute pain lasts for a short amount of time, most often seconds to minutes, sometimes days, sometimes weeks. But the thing here is that we usually recover from acute pain. The cold goes away, the sore throat goes away, the headache goes away and you're you're broken ankle heals. What is chronic pain? The definition here is pain that lasts for a much longer period of time. Here, we're talking about pain lasting at least three to six months or longer. Oftentimes, chronic pain patients are experiencing pain over years. Again, what's discouraging here is that for chronic pain oftentimes it's not treated successfully. That chronic nature is it makes it very difficult. It also is very difficult for patients and healthcare providers to try and understand why is this chronic pain not going away. There's not always an obvious source and as I mentioned before, oftentimes there's not a treatment that is effective. So this critical question you see at the bottom of my screen here is why do some people develop chronic pain following injury, while others don't? Some people get injured, the injury heals, and they're perfectly fine and some people get injured, injury heels and they develop chronic pain that last for years. So examples of chronic pain and the probably the most prevalent examples are lower back pain, but also neck pain, jaw pain, joint pain, headaches, arthritis and cancer pain. They're all different types of pain. These are some common examples I list here. Even though there are different examples of pain, these oftentimes are viewed in terms of the type of pain. There are three or four groupings that makes sense in terms of the biology and those are called nociceptive, inflammatory, neuropathic, and dysfunctional. So immediate stimulus driven pain that is nociceptive in nature is triggered by an encounter with some stimulus, whether it's heat or it could be acid or chemistry or it could be pressure. But that is how the pain signal is triggered. Illnesses like arthritis or cancer can produce persistent nociceptive pain, so there is persistent signaling. Again though as I mentioned before, nociceptive pain is normally adaptive. There's an important reason why we're supposed to experience pain when we touch a hot object. It's also important to note that when people don't have that adaptive response bad things happen. For example, people who are born with congenital insensitivity to pain can die because they don't feel the injury in time to change the outcome. The same thing is true for diabetics. This pain signaling mechanism, this nociceptive pain, is normally adaptive and it's important. There are three other types of pain and we'll talk about inflammatory, dysfunctional, and neuropathic. These types of pain are summarized in this figure here which was taken from a paper in Nature Neuroscience from 2002. It's an old paper but I think a nice graphical depiction of what we're talking about here. The other reason I like this graphic is that in terms of listing some of the mechanisms in terms of the signaling what you can easily do, if you are interested in doing a deeper dive here you can Google for example TRPV1 and CBD, and maybe begin to see some connections between cannabinoids in some of these signaling mechanisms. But in any case, these are the mechanisms that signal the pain. That signal basically travels along nerves through the spinal cord up to the brain that creates the experience that we all have when we encounter something painful. Inflammatory pain. Inflammatory pain takes place after tissue injury and after inflammation occurs. So basically, there's a change in the system that involves inflammation and responsiveness such that even normally benign stimuli or mild stimuli can cause or produce pain. In addition, response to the painful stimuli are typically more pronounced and prolonged. Inflammatory pain usually disappears after initial injury is resolved. However, in chronic conditions the pain can persist after the inflammation is no longer active. Again, in chronic sense that inflammatory pain can continue. In some ways it's like a form of pain hypersensitivity. When we look at the animal literature, there's definitely a link there between pathological pain and immune system function in the central nervous system and periphery. So again, this type of pain involves immune system functioning and inflammation. Peripheral inflammation can also impact neuro immune signaling, both in the CNS and in the periphery. This is important. Neuropathic pain is basically pain associated with nerve damage. We have peripheral neuropathic pain. We have central neuropathic pain. It can occur in the absence of any identifiable pain stimuli. Where does it come from? Well basically, it comes from damage to nerves and that damage can result from infection. It can result from tumors or trauma or metabolic disease, spinal cord injuries is a big one, a stroke, MS and we'll talk more about some of these in future modules. What does it feel like? What do people experience? Well, oftentimes it's a burning sensation, it's a pins and needles sensation. Sometimes you will experience pain just by clothes touching your skin, it's like putting on a shirt. Normally, something that would not be painful, but in the context of neuropathic pain, in the context of nerve damage can be very painful. The mystery here as I mentioned before is the persistence. Why does the pain persist? That's a difficult question for healthcare providers to answer. Patients find it very discouraging to think about. But it is this important question about why some people recover from acute pain while for others it turns into chronic pain. There has been a lot of research on this topic and there are some important variables that can either exacerbate this or potentially make it better. We're going to spend a few slides talking about that. This slide show shows you the different factors that can influence the experience of pain. Here we have our pain experience and our pain signal up here. But these over here are things that influence that pain experience. The way we think about the pain is important. The emotions that go along with the pain are important. Our social environment or social factors are important and our behavior. All of these things can influence either exacerbate or mitigate the pain experience. How does it work with emotions? Well, pain itself is an emotional experience. Obviously, people are experiencing emotions that go along with this chronic pain and things like fear, depression, and anger often accompany pain. Negative emotions are another source of inflammation to the brain. The brain is receiving information both about the pain itself, but also about these emotions. We know that the stronger the negative emotion, the greater the perceived level of pain. That is how emotions work especially negative emotions. With cognitions its a similar kind of thing. These negative cognitions, negative thoughts like: "This is horrible", "I'll never get better", "I cant survive this pain" or "My life is ruined". All of these thoughts strengthen the pain signal and make pain worse, make the experience of pain worse. Besides amplifying the signal, negative thoughts also can diminish a person's self efficacy. That is that the degree to which they're confident that things can get better. Of course, that's important because you need some self-efficacy in order to effectively manage your pain. This is very important. Also, the social environment's also important. There isn't interpersonal contexts to this. We have people around us, family, and friends and their responses can make things better or worse. If they're overprotective, over solicitous, or maybe they just ignore everything, or they're negative or punishing, all these things can make pain worse. Some common responses to pain. Sometimes family and friends can be overbearing. Sometimes they're overbearing since they're really trying to help which is nice. But if it reduces a person's sense of control and self efficacy that actually can make it more difficult to manage pain. Discouraging a chronic pain patient from exercise or activity because you're trying to help them or protect them, that can make things worse over the long run too. Criticizing, abandoning, spending less time, ignoring people with pain can also cause feelings of depression and loneliness. The interpersonal interactions are very important in terms of the experience of pain. In terms of behavior, some kinds of behavior can make pain worse. It's natural of course to favor a part of your body that is hurt, but over the long run that can be counterproductive. The injured part of the body can become weaker if it's favored and more prone to injury down the line. People with pain may also avoid situations they fear may make their pain worse. Avoidance has physical as well as psychological and social costs. Pain may also make it difficult to sleep, and we know that lack of sleep can worsen the experience of pain. Also, misusing or abusing alcohol and drugs, especially opioids poses both pretty severe health risks, but also in the long run can make pain worse. These are all behaviors then that can influence the experience of pain. Chronic pain carries with it a significant burden. This comes from a paper this graphic. It's cited down here at the bottom of the screen. You can imagine people who have chronic debilitating pain. There certainly are socioeconomic consequences. There are issues in terms of healthcare costs and lost productivity. There's the emotional side of things. There's the social consequences in terms of problems with marriage and family relations, and of course it can certainly take a toll on activities. It can disrupt sleep and work and leisure activities and so forth. Definitely, the chronic pain carries with it a substantial burden. To summarize chronic pain is pain that last for months or years. It's complicated at both the biological level but also at psychological level. The etiology that is the cause of the chronic pain varies from person to person. Oftentimes, it's very difficult to understand why it's chronic and where it's coming from. Of course, there are a number of impacts, negative consequences at the social, emotional, and behavioral levels can be very debilitating and can carry a substantial socioeconomic burden not just for the patient but also their family.