Activity Transcript

SEGMENT 1

Jo Nijs, PT, MT, PhD. Hello, I'm Jo Nijs from the University of Brussels and University of Gothenburg and University Hospital Brussels. And I will show you how you can differentiate between neuropathic, nociceptive, and nociplastic pain, and how this can improve your treatment, including pain medication. Of course, you can also have mixed types of pain. But in general, these are the 3 major types recognized by the International Association for the Study of Pain, the IASP, and the IASP also created the definition of the most recent type of pain recognized by the general pain science community, and that is nociplastic pain. Of course, the mechanism of central sensitization is the underlying mechanism which is presumed to be fairly responsible to a large extent for the nociplastic type of pain. But of course, remember that there is also peripheral and central sensitization involved in other pain states, including neuropathic pain.

I will guide you throughout the differential diagnosis between those 3 major types of pain using a case study from Ms Ni. And Ms Ni is 54 years of age. She's suffering from knee osteoarthritis for more than 10 years now.

So we do the differential diagnosis between those 3 major types of pain. And the first thing we need to do is to ask ourselves, "Okay, is she suffering from chronic pain?" Because you can only differentiate between those 3 major types of pain as soon as we're talking about chronic pain, that is pain of at least 3 months duration, which obviously applies to the case of Ms Ni. The second question we need to ask ourselves is, "What about the pain distribution? Is it regional or more widespread?" And then when we look at her pain drawing, we can obviously see that the pain is spreading beyond the knee area. She obviously meets this second criterion of spreading of pain beyond the presumed area of nociception.

And then the third criterion relates to differentiating between nociceptive and nonnociceptive pain. And then we ask ourselves, "Okay, does Ms Ni present with nociceptive pain? And if she does, is it entirely responsible for her pain and suffering? And here you see the results of the imaging findings. There is some limited knee osteoarthritis identified. The pathology identified can potentially cause some type of nociceptive input, but probably not enough to explain her full clinical picture. Because the pain and suffering is much more severe than suggested by the magnetic resonance imaging (MRI) findings. Of importance here is also that the most recent MRI outcome is nearly identical to the MRI findings from a couple of years ago when she was suffering from much less pain. So you see that there is not a clear association between her pain and suffering on the one hand and the MRI findings on the other hand. And this of course makes us conclude that there is something else going on besides just the nociceptive pain mechanism. Of course, there is obviously an osteoarthritis, but this is creating a continuous bottom-up input which is triggering changes in the central nervous system, including in the spinal cord and of course in the brain. And this of course creates changes which relates to central sensitization, which are then held responsible for the feeling of her pain, the large pain extent, the spreading of the pain beyond the area of presumed nociception. So we conclude that the third criterion is not met and we have to look at other possibilities for her pain.

So we proceed to the fourth criterion, which is identifying or excluding neuropathic pain as a possibility for explaining her pain experience. And the main thing of course of neuropathic pain is that there has to be a neurological lesion or a disease. In her situation, the situation of Ms Ni, there is no such damage to the peripheral or central nervous system, so we can exclude the possibility of neuropathic pain, as is most often the case in knee osteoarthritis. So then we have already excluded the possibility of pure nociceptive pain. We have excluded the possibility of neuropathic pain, but before we can conclude that we are dealing with nociplastic type of pain, we have to explore whether additional symptoms are also present to match the criteria for nociplastic pain, including the evoked pain hypersensitivity criterion, which is fairly easy to assess in the clinic by gently stroking the skin with a brush or cotton buds, but which we did with Ms Ni. And that turned out to be positive. We also palpated with approximately 4 kilograms of pressure, and that turned out to be painful as well. If you wonder how to do that, just use your thumb to increase the pressure, and as soon as your thumbnail becomes white, then you have approximately 4 kilograms of pressure. And only 1 of those symptoms should be positive. So we didn't proceed with Ms Ni to testing her sensitivity to cold or warm objects, such as heating a metal object to 40 degrees Celsius. Anyway, she fulfills the fifth criterion of evoked pain hypersensitivity, then proceeds to the sixth and the seventh, which is the final criterion about history of pain, hypersensitivity, and comorbidities.

Regarding history of pain hypersensitivity, she has hypersensitivity to activities, body movement, and also to touch, and mechanical pressure because of course, wearing her shoes that used to fit very nicely is nowadays an issue. And she also has severe sleep problems. And if there is only 1 sign of pain hypersensitivity plus 1 comorbidity, then that's enough to fulfill these criteria. Then, you don't need to screen for the other comorbidities or pain hypersensitivity symptoms.

So we conclude that yes, she also fulfills the sixth and seventh criteria, and therefore we conclude that she has probable nociplastic pain. And this is present not only in a knee osteoarthritis, but also in other types of osteoarthritis and in many other typical chronic pain diagnoses. It's also very common in postcancer pain, in pediatric pain. It's available across all medical disciplines, and therefore, we created a central sensitization continuum. You can place your individual patient on this continuum. The goal of the treatment is to reposition it throughout the treatment progress more to the left part of this continuum, because patients do vary over time in the amount of severity of central sensitization. It's important to recognize this, the mechanism of central sensitization as the underlying driver or mechanism of nociplastic pain, because when it's present, it should guide your treatment because we know that central sensitization predicts poor outcome following surgical interventions. It also predicts poor outcome following nociceptive targeted procedural treatments or conservative management for chronic pain.

So in general, if there is nociplastic pain, you should target the central mechanisms rather than the peripheral mechanisms. In the case of nociceptive pain, you target peripheral mechanisms by providing peripherally acting drugs, such as nonsteroidal anti-inflammatory drugs, or any other kind of peripherally acting drugs. In the case of neuropathic and nociplastic pain, you use centrally acting drugs, such as serotonin and noradrenaline reuptake inhibitors or any other kind of centrally acting drugs; but, don't use opioid drugs for too long, especially not in the nociplastic type of pain because in general, patients with nociplastic pain, they have increased sensitivity also to drugs, so they respond with much more side effects also to centrally acting drugs, and therefore, in nociplastic pain, in general, the international guidelines state that we should target the chronic pain problem by using a conservative approach, by providing a multimodal lifestyle-targeted approach to managing the pain.

Of course, in this presentation, I only dealt with the differential diagnosis between nociceptive, neuropathic, and central sensitization or nociplastic pain, but be aware that you should of course comprehensively assess your patients. So also consider all the other factors listed on the left part of the slide because they are equally important for guiding your multimodal treatment for managing chronic pain. Thanks a lot for listening to me, and I wish you the best of luck with applying this in clinical practice.

SEGMENT 2

Vered Simovich, MD: Hello, I'm Vared Simovich, founder and former chairwoman of the Pain Management Society of the Israeli Family Physician's Association and Family Medicine expert at the Maccabi Health Services in Israel. Welcome to this segment titled, "What Do We Know About Opioids for Pain?" As we begin our journey in the pain pathway, we see that from the periphery, stimuli that begins at the periphery goes through the spinal cord and into the brain. Each and every station can react to the use of opioids in reducing pain.

So let's look at the patient and ask him if the pain is severe enough that it requires the use of opioids. We might do that by using a VAS scale, which is a visual analog scale of very simple and subjective, as pain is, to the measurement of pain. It goes from 0 to 10 or from 0 to 100, and any pain above 6 and more [on a scale from 0 to 10] can require the use of opioids. Have alternate treatments been tried and are they inadequate or intolerable? Did they cause side effects which meant the patient could not go on using them? And are the benefits of using the opioids expected to outweigh the risks? The patient at low risk has no history of substance use disorder, not now, and not in the past. They do not have a history of this in their family and have no major or untreated psychological disorders. The patients at moderate risk do have a history of a substance use disorder or a significant one in their family, and a past or current psychological disorder. And as we go to the high-risk patient, they have now active substance use disorder, an active addiction, or a major untreated psychological disorder. And in this patient, we should consider not using opioids as a treatment for pain.

Remember, pain patients that are on opioids are not touch and go. We need to invite them again and again to assess the benefits of the treatment for them. And I suggest now a 4A questionnaire that you can use in a very short and normal encounter at the doctor's office. Number 1, is there a measurable analgesia? Remember we use the VAS score at every meeting and if the patient said that the first pain was around 8, we need to see a gradual decrease by using opioid at least to 4 or less, if the patient is responding to the treatment. What changes are there in activities of daily living? Can the patient sleep better? Do they go to work? Do they help with the house chores or go out with friends and drink a beer or go to a movie? Things that they couldn't do before? If they do this, then the treatment is going well. Is the patient experiencing any side effects? Remember that the side effects are also show us that the patient is actually using the drug. And if they do suffer from side effects, it is our responsibility to help alleviate them. And are there any kind of aberrant drug-taking behaviors? Does the patient come very often to ask for more of these drugs? Does he go to other doctors and seek for it or does he tell you that he lost the prescription or his wife threw it down the toilet or anything else? Aberrant drug-taking behavior should raise a red flag for us as doctors as to the continuation of this treatment.

Let's talk about the most common terms in the use of opioids and let's begin with addiction because this is the thing that we fear more as doctors and also our patients fear it. And let's understand that addiction is a primary chronic neurobiological disease. It's a disease like any kind of other disease with genetic, psychological, and environmental factors that influence its development and manifestations. It is characterized by behavior that includes 1 or more of the following: impaired control over drug use, compulsive use, and continued use despite harm and craving. Addiction is estimated to have an overall prevalence of 3.3% in patient receiving them for chronic noncancer pain, while aberrant drug-related behavior is much more prevalent.

Dependence, unlike addiction, is a state of adaptation that manifests by the drug class-specific withdrawal symptoms that can be produced by abrupt succession of the drug, rapid dose reduction, decreased blood levels of the drug, and/or using an antagonist. It is a pharmacological reaction, nondependent on the user. We do not discontinue opioids abruptly.

Tolerance is a need for markedly increased amount of the opioids to achieve intoxication or desired effect. For example, pain reduction. And in this case, we should consider uprising the dose. Evidence suggests that analgesic tolerance occurs at a very low frequency. So we should not be so afraid of tolerance and dependence. We just should manage them very, very carefully and cleverly.

As you can see, we have many side effects, beginning with nausea and vomiting, feeling of sedation, itching, respiratory depression, which we fear so much, but it's not very common in the community setting of opioid treatment. Myoclonus and sweating. As you can see, tolerance to this side effect typically develops with long-term treatment. Unlike that, the peripheral side effects are a little bit more tricky. We can see gastrointestinal (GI) tract side effects, hypertension, and urinary retention. All of them are not alleviated by tolerance and especially the GI side effects.

We tend to think that only constipation is the main side effect caused by opioids, but in fact, they influence all of the GI tract from the beginning to the end. As we speak about opioid-induced constipation, it is a phenomena in up to 90%, some might say 100% of patients using opioids, and it affects deeply the quality of life. We develop no tolerance to the side effect. We do not speak about it very often with our patient because it is an embarrassing question for us and maybe for the patient in front of us. So we underrecognize it and undertreat it and often it is treated ineffectively. Because the drugs that we use like laxatives and stool softener are only a symptomatic relief and do not tackle the cause of opioid-induced constipation. They're often ineffective and may cause habituation by themselves. A drug that is composed of oxycodone and naloxone, has effective analgesia similar to that of oxycontin. It does improve the bowel function. The naloxone has a higher affinity to the mu receptors along the bowel, so it binds to these receptors causing the oxycodone to be able to continue to do its effect on the pain in pain reduction. It is of significant and clinically relevant importance in constipation with compared to using only oxycontin. It treats the cause of opioid-induced bowel dysfunction and prevents constipation unlike the laxatives.

We can see that long-term effects are opioid tolerance, as we spoke about before. They can cause immune system depression, hormonal changes in the hypothalamic pituitary adrenal axis, which can be seen as decreased libido, aggression, amenorrhea, irregular menses, and galactorrhea. Hyperalgesia - bear in mind that using opioids for long term can cause the opposite effect and cause hyperalgesia and the patient should report it. And you should know that this is a side effect and consider discontinuation of the drug. Motoric and cognitive impairment - and as we speak about this impairment, we cannot ignore the effect on driving. People on chronic morphine use were affected in driving, with slower reaction times, making more mistakes, slower ability to process visual information, but all of this was seen as not statistically significant. So if someone is on opioids, we might tell him to avoid driving or not drive while he is beginning the treatment or while he's increasing the dose of the treatment that was already given to him. Try to avoid driving at these moments.

What kind of patient advice should we give general recommendation to people who are taking the drug? Well, the best way to dispose of them is of course, is to drop the medicine at a drug take-back site, location, or program immediately as soon as they finish the treatment. But furthermore, we should store opioids in a locked container. We should keep opioids in their original packages. Anyone that touches this know that it is an opioid. We should obviously keep them out of reach of children. We do not share our medication. The medication was prescribed for you and you alone. Safely dispose as we spoke before of unused pills and we take special care, try to avoid and or/use another specialist if it comes to use it in pregnant or breastfeeding women.

So what are our conclusions? Opioids can kill, but cars can also kill. Should we blame the cars for accident-related death? So I tell to all of you, when used properly by adequately trained doctors, with accurate diagnosis of pain condition in the right patient, opioids are effective and safe drugs to treat moderate to severe pain. Thank you all for listening to this segment on using opioids for pain treatment. Bye.

SEGMENT 3

Mehmet Ungan, MD, PhD: Hello. I'm Mehmet Ungan, a professor at the Ankara University School of Medicine and Department of Family Medicine in Ankara. And I am also a practicing family physician. I was the past president of the Turkish Association of Family Doctors, and past president of the World Organization of Family Doctors Europe. Welcome to this segment titled, "Using Nonsteroid Anti-Inflammatory Drugs Appropriately."

We all know that prior to initiation of any nonsteroid anti-inflammatory therapy, we have to screen for cardiovascular diseases, gastrointestinal diseases, and rare risk factors. In many meta-analyses, all nonsteroids including naproxen were associated with an increased risk of gastric ulcers, acute myocardial infarction (MI), and renal failure, and most increased the risk of heart failure. The real-world data also suggests a heightened cardiovascular risk with nonsteroid anti-inflammatory use.

So, it is recommended that patients with risk factors for renal impairment have preventive strategies in place that include using the lowest effective nonsteroid anti-inflammatory dose for the shortest possible time, as well as monitoring renal function, fluid retention, and electrolyte abnormalities. The concomitant use of nonsteroid anti-inflammatories and angiotensin-converting (ACE) enzymes, ACE inhibitors, should be avoided. The third trimester of the pregnancy is a condition for contraindication. Also, suspected history of nonsteroid anti-inflammatory hypersensitivity is an issue that we should be careful of.

One may think that there can be a direct effect of any pill in the stomach, but the nonsteroid anti-inflammatory drugs usually block the prostaglandin production and also block the barrier of the mucosa. Then that means that the gastric tissues are prone to the direct effect of the acid because the old preventive layer is lacking. So, this is the mechanism.

So, what happens? The majority of patients develop some gastric erosions after each dose of nonselective nonsteroids. So, 15 to 30% of the patients taking these drugs develop ulcers seen by endoscopy at one time or another and these are usually silent lesions. So, what does that "silent" mean? Just imagine how we are fearing of asthma, cervical cancer, Hodgkin diseases, HIV, leukemia, but you can see here that nonsteroid anti-inflammatories are also causing deaths. And this is a silent epidemic because we think that they are harmless.

The risk factors for development of [complications of] nonsteroid anti-inflammatories are, as I mentioned, gastrointestinal, cardiovascular, and renal. There are 2 blocks. One of them is the definite risk factors, and the other one is the additional possible risks. Definite risk factors are ulcer history, concomitant use of anticoagulants, advanced age, which is over 65 [years] or in some studies older than 60 [years], high-dose nonsteroid anti-inflammatory use, multiple use of nonsteroids, concomitant use of steroids, and concomitant use of hypertension medicines, diuretics, and renin-angiotensin inhibitors.

Also, severe comorbid diseases such as diabetes, coronary artery disease, liver disease, and kidney diseases are the definite risk factors which we should keep in our minds. Helicobacter pylori, tobacco, alcohol, and a glomerular filtration rate less than 60 are additional possible risk factors.

Once you have a patient and you want to start on nonsteroid anti-inflammatory medication, you plan it. If you see that your patient has never used nonsteroid anti-inflammatory so far, consider possible risk factors. If the age is younger than 65 [years], no other risk factor, no need for primary prevention when you start. But if there are other risk factors like Helicobacter pylori, you have to eradicate before you start. Or if history of ulcer is present, anticoagulant concomitant use present, an age 65 [years], over 65 [years], steroid, high-dose nonsteroid anti-inflammatory use, aspirin use, comorbidity, then we have to have a primary prevention recommendation.

There are several aspects that define pain and its effect. I will not go forward too much, but pain severity, chronicity, and pain experience are 3 main items in primary care, especially that we consider. And you all know that these pain rating scales, the visual analog scales are in use in our primary care centers and family practice.

Self-diagnosis and treatment with over-the-counter (OTC) drug is another issue in our lives. What are the benefits of self-diagnosis and treatments with OTC drugs? Easy access to medication, quicker relief of symptoms, convenience, increased access and empowerment. Patients can take some control over their health care, but it is very important to be very careful to acknowledge them, to educate them before we medicate them. This is important.

And what are the risks of self-diagnosis and treatment with the OTC drugs? Potential delays in diagnosis and treatment of serious illness, overuse or inappropriate use of medications, lack of awareness of adverse events and how to manage them, lack of awareness of drug and drug interactions between OTC and prescribed medications, lack of awareness of effects of OTC drugs on chronic conditions. Those are the risks also of the OTC drugs.

So, there is an efficacy for pain, of course, and the nonsteroid anti-inflammatory drugs usually affect muscular pain, headache and backache, third motor extractions, such kind of problems, while acetaminophen is used for dental pains, soft tissue injuries, and osteoarthritis of the knee.

Let's see the safety warnings again. Gastrointestinal adverse events warning with ibuprofen, naproxen: inflammation, bleeding, ulceration, perforation, cardiovascular adverse events, thromboembolism, myocardial infarction, stroke, and elevated blood pressure. What are the contraindications? Definitely, peptic ulcer disease, hypertension, and chronic kidney disease.

So, before we leave this video, let's say, I can tell you that we have to advise to our patients using nonsteroid anti-inflammatories frequently. We have to empower the patients as they are close to the over the counter from pharmacies, which may also be harmful while expecting to be usable. So, they have to talk with us and we have to talk with them before using it. And we have to advise them to avoid using medicines of their spouse or neighbors or friends without consulting to their own general practitioner (GP). And if nonsteroids are not suitable, we may suggest alternatives, such as paracetamol.

Some nonsteroids can react unpredictably with other medicines. This can affect how well either medicine works and increase the risk of side effects. It is particularly important to get medical advice before taking a nonsteroid anti-inflammatory, if one already taking another medicine. What can those medicines be? Another nonsteroid anti-inflammatory, low-dose aspirin use for preventive purposes, and some medicines which are preventing the blood clots. And some antipsychotic medicines, anti-psychiatric medicines, lithium, selective serotonin reuptake inhibitors (SSRIs), and many other medicines can interact with each other.

Of course, 1 very important thing is any unusual new symptom is a red flag when you use nonsteroid anti-inflammatories. We have to tell it to our patients. If we are or our outpatients are bothered about side effects, then we have to stop it and ask a specialist colleague to evaluate the condition. Thank you for listening to me.

SEGMENT 4

Daniel Ciampi de Andrade MD, PhD: Hello, everyone. My name is Daniel Ciampi de Andrade. I'm glad to be here, with Medscape Educational Global, covering the topic on pain medication in patients with . . . in special populations of patients.

The first group we are covering is the older or frail patients. This, we know that chronic pain is more frequent with advancing age, and we try to use nonpharmacological approaches, but sometimes pharmacological treatment is necessary, and these patients may be at a high risk of fall. We have to remember that fall is a very common cause of death and impairments in the elderly. And when prescribing drugs that may have central-acting effects, we have to always remember to tell patients some general advices to prevent falls. Some basic and very simple things. For example, turning on the light at night or leaving a light close to the floor when they wake up at night with prostate hyperplasia in a case of a man.

This may help prevent falls, and also never leave clothes on the floor, or try to remove as much as possible objects and everything from the floor, for example. And always remember that patients, with age, they have more diseases, and the risk of polypharmacy, the risk of having several drugs prescribed for the same patient, exists.

Sometimes patients may visit other doctors, and sometimes they may even be taken the same drug with different names. So it's always a good practice to ask patients exactly what they're taking, what they're actually taking, because sometimes a drug is prescribed but not taken. And when possible, we may try to use 1 drug to treat 2 symptoms. There are several examples of situations of drugs, for example. Gabapentinoids, for example, they may help neuropathic pain, but they are also anxiolytic, and they're also drugs that may increase the deep wave-less sleep, it may improve sleep quality. So that's 1 strategy, for example.

Always, patients with advancing age, they are in high risk of renal and hepatic impairment. We will cover these topics in a little while. And remember, cognitive dysfunction is more common. Cognitive dysfunction may impact the way patients understand what we are talking to them. So it's always good practice if you have a nurse, a physician assistant, or if you have time, try to create a table with the drugs, and make sure that the patient receive the actual drug the right way. Patients with cognitive impairment, they may have a hard time understanding what we tell them and the way to take the drug. So it increases the risk of side effects. So some tips, ask for a caregiver. Some patients they cannot come along to the consultation, so either a joint family member, ask for someone to come with them, it can be a friend. Remember less is more. As I mentioned, try to use sometimes one medication to treat 2, sometimes 3 conditions or symptoms. And as always, that's a general advice in geriatrics, go slow, starts slow and goes slow. You don't need to start with very strong dosages.

Liver impairments can be a problem. We have to remember that we have to know the drugs. Some drugs may be hepatotoxic. In the pain field, we have to remember very simple over-the-counter drugs may affect the liver, such as paracetamol or acetaminophen, for example. And some drugs may have an impact in special populations.

In some countries, we run polymorphisms of the cytochrome P450 genotypes, but sometimes we cannot do this. And we have to remember that one drug may have very different effects in different people. Some people will never respond to tramadol, for example, or to codeine, 10% of White people, because they will not metabolize these drugs. Sometimes it's a problem with absorption. Sometimes it's the way the drug is metabolized.

And remember that some drugs are not metabolized in the liver, and some are not metabolized at all. So when we have liver impairment, these would be the ideal drugs. It doesn't mean that the patient will not have side effects, because if the drug . . . the patient with liver dysfunction, he may have a higher chance of having delirium and cognitive attentional oscillations. So if we give smaller dosages, at least we know we are not aggravating the liver problem. For example, gabapentinoids, which are not metabolized, for example.

Some tips, adjust the dosage, watch for drugs that are falsely innocent. Some patients are already taking over-the-counter drugs, they don't tell the doctor. And when you prescribe something else, it may interact and worsen a liver impairment, because the patient is actually taking 2, 3 drugs that will affect the liver.

And just watch for hidden enemies. Alcohol is a classic example. Patients may not report that they're drinking alcohol more than they should. And also benzodiazepines, which is also a pandemic, but we haven't talked about it that much as much as opioids. And just remember, drugs that are not metabolized by the liver, it doesn't mean the patients will not have side effects, so we still need to worry about the dosage.

Okay, another topic is patients with renal impairment. And here there's a very important distinction. One thing is, when we're talking about drugs that need to be adjusted based on the renal function, but it doesn't mean the drug is nephrotoxic. It's not the same thing. So some drugs are just nephrotoxic, you should never prescribed when patients are in renal insufficiency. And you should always pay attention, even in normal people, when prescribed these drugs, for example, NSAIDs. But some drugs are simply in need of an adjustment, because they are, in part, directly or some metabolite excreted by the kidneys. So you need to adjust to the renal function.

And remember, these calculations, they're based on pharmacokinetics. They may not work, so you may also monitor. You need to monitor. Even if you do all the calculations and if you calculate the clearance of creatinine and adjust the dosage, it may still be needed to decrease a little bit the dosage, or sometimes increase a little bit. Just remember that pharmacokinetics is not pharmacodynamics, so what we calculate in the ideal world when we treat patients and we have different types of metabolism, it may be slightly different. So we have to be watchful and follow up these patients.

Some tips, we have to check the last renal function of patients before we prescribe these drugs, and order new ones and monitor. We have to remember that some drugs are less impacted by renal function. And always check the dosage and adjust continuously. It doesn't mean that just because you calculated the adjustment that the patient will be fine. You have to monitor.

Pregnant and breastfeeding patients. Well, think about nonpharmacological options first, because it's always an issue. But at the same time, if you need to treat patients that have very strong pain, don't hesitate to treat them. So we have to find the balance between both strategies. Remember 1 thing, all pregnancies carries some risk. The risk of malformations in general, it's 1% to 2% of all the pregnancies. So we have to tell the patients this, because sometimes you're given a drug that increases the risk by 10% or 15%, but the risk is already 2%. And sometimes increasing the risk of by 10 or 15%, you're moving the 2% risk, which is a baseline risk, to 3 or 2.5. So it doesn't mean that the risk will go to 15%, it's just an increase of an already-existing, but slow or low risk.

We have to check the classification of the drugs, that's super important, of course. And always involve the patient. Explain that all pregnancies carry a baseline risk. And the patient has a disease, otherwise he wouldn't be with you, so you have to explain that sometimes the disease itself may carry a risk. If the patient doesn't take drug treatments for pain, for example, but then they go to the emergency room every week to take opioids, they're taking the worst, maybe not taking the best drug anyway. Sometimes the patient will need a treatment anyway. And share the decision-making process. It's always nice to talk to the obstetrician and share the decision with the obstetrician, for example. And sometimes the pediatrician.

Coming to kids. First message, kids have pain. Second message, yes, they do have pain. It's very often forgotten that kids may have chronic pain. Headaches and migraine in kids are very common. Extremely common. Even though it lasts just a little bit, it doesn't last as long as in adults, so sometimes pain goes away, and we think the kids were not really in pain, but they do have pain. We have to assess pain directly if they're 5 years old or older, older than 5 years of age. Otherwise, we need to rely on the report from caregivers, parents, or from behavior. But we need to assess pain looking at the kid. For headaches, we have a lot of guidelines related to, specifically migraines, related to treatment of kids. It will be interesting to take a look at those guidelines. And education is fundamental. Kids can learn. And you can teach the parents and teach the kids how to avoid situations where they will endure pain, that may cause pain.

So as summary, remember, no patient has chronic pain. Chronic pain only exists in prevalence studies. Patients have a specific pain syndrome, and this pain syndrome has a name. Migraine, low back pain, nonspecific low back pain, fibromyalgia, cancer-related pain, nociceptive pain, osteoarthritis-related pain, whatever. Not all treatments are pharmacological, but if treatments are needed, and pharmacological treatment is needed, don't wait too long. Remember to avoid the general complications of centrally acting drugs or polypharmacy related, especially in the elder folks, renal liver impairment.

And obstipation. Obstipation in patients can be worse than pain. There's a lot of classical studies from the '90s showing that patients with cancer and chronic pain related to cancer, they sometimes prefer to be with pain. And no obstipation caused by opioids, so it's important to think in advance, and sometimes prescribe medications or interventions or strategies to try to compensate for potential side effects before they occur, because they are so common. And monitor patients close and listen to them. Remember, a good patient-doctor relationship is the first step in functional improvement. And functional improvement is our main aim. Treating pain is a way to have functional improvement. It's a means, not an end. Thank you.

This transcript has not been copyedited.