Hello, and welcome to Understanding and Assessing Opioid Use Disorder in Patients with Chronic Pain. My name is Sarah Edmond, and I'm a research psychologist at VA Connecticut and assistant professor at Yale School of Medicine. We have a few housekeeping notes, as you can see here on the screen. All of the disclosures have been reviewed, and there are no relevant financial relationships with ineligible companies to disclose, and I have no disclosures. As far as our educational objectives for today, at the conclusion of this activity, participants should be able to discuss components of a neurobiological framework and explanatory model for patients with chronic pain and opioid use disorder, describe complexities involved in differentiating opioid use disorder from chronic pain, identify key features of opioid use disorder, and review how to perform an opioid use disorder evaluation in primary care. We have two cases to guide our discussion today. Our first case is a 35-year-old female with chronic daily migraine and diffuse myofascial pain. She's been prescribed opioids for five years following the birth of her daughter. This patient experiences severe depression and anxiety, chronic nausea, and has a history of adverse childhood experiences, specifically neglect. Additionally, obesity is a concern. As the primary caregiver for two children, she frequently has to place her children into daycare due to the severity of her migraines. She's on high-dose benzodiazepines prescribed by a psychiatrist, and the patient has a history of losing opioid prescriptions, obtaining opioids from multiple providers, reporting allergic reactions to non-opioid pain medications, missing appointments, and frequently asking for opioid dose increases. So keep her in mind as we go through this presentation, and now we'll also talk about our second case. Our second case is a 62-year-old male with chronic pain at multiple sites, including row back, bilateral knee, and bilateral hip pain, who you are now seeing as their primary care provider due to the retirement of their former primary care provider. His medical history includes polyarticular arthritis, bilateral knee replacements, light hip replacement, and PTSD. He's currently prescribed morphine short-acting 60 milligrams three times a day, oxycodone extended release 10 milligrams Q6 hours, and opioid therapy started in 2004 at 30 milligrams morphine-equivalent daily dose, now escalated up to 240 milligrams morphine-equivalent daily dose. Historically, he's taken his opioids as prescribed. He's had two early refills in the last six years. His urine drug screens and prescription drug monitoring program checks have been consistent with prescribed therapy. He's generally sedentary with intermittent high-intensity activity. He has daily moderate to severe pain interfering with his ADLs, mood, and relationships. And he also reports nightmares, snoring, and erectile dysfunction. Some thought questions for both cases as we go throughout the presentation. Does this patient have pain? Does this patient have an opioid use disorder? What factors place this patient at risk for an opioid use disorder? What can you do to help this patient? Hopefully, by the end of the lecture, you'll be able to answer all of these questions. Whatever its cause, when pain persists, it often causes secondary problems that, in turn, can facilitate distress and pain. Many of these relationships are bidirectional in nature. We know that pain often leads to sleep disturbance, secondary physical problems, anxiety, depression, exacerbation of PTSD symptoms. Autopain is also sometimes associated with cognitive distortions, increased stressors, and all of those can lead to declining function. Substance use and misuse is another element in the picture of persistent pain for some. As a chronic condition, opioid use disorder shares similar challenges as persistent pain, contributing to many of the same issues we just mentioned. Similarly, many of these problems can potentiate the use disorder itself. So these two chronic conditions have many of the same underpinnings and many of the same secondary challenges. As shown here, you can see that pain and opioid use disorder can also reinforce one another. So when they co-occur, you need to address both to successfully treat either one. When we do, we can more effectively treat both pain and OUD. And you can see here that not only do pain and OUD reinforce each other, but many of the secondary causes reinforce pain and OUD as well. So what is the underlying neurobiological mechanism that explains the complex interaction between pain and opioid use disorder? There's now quite a bit that we know about this process, which we'll discuss in the next several slides. Initially, pain research focused on how sensory systems change and signals get amplified. And while this is true for acute pain, as pain becomes persistent or chronic, the sensory changes become less important and the modifications in the emotions and reward processing systems start to be more involved. Here you see that displayed with some fMRI data. At three months after an initial injury, the brain regions involved in pain shift away from the sensory systems and to the emotion and reward systems. So reward learning processes may contribute to persistence or amplification of pain. In order to understand that shift, it's helpful to revisit the neurobiology of reward and emotion, which is eloquently described by Dr. Koob in the Neurobiology of Addiction. As Dr. Koob says, addiction has color-coded things for you. There are three different stages of addiction that promote drug-seeking. Bloom is the binge intoxication stage, red is the withdraw negative affect stage, green is the craving stage, or the human stage as Koob calls it. So these are the systems that are involved in substance use. First, the blue part, the binge and intoxication step, involves the basal ganglia, affects motivation for a substance via dopamine and opioid peptides, and also plays a key role in pain relief seeking. The second system involved is the system of withdraw and negative affect stage, and this is in the nucleus accumbens and the amygdala. In this system, over time, we see loss of reward, dysphoria, pain, and anxiety. The third stage of addiction that promotes substance use is preoccupation and craving, seen in the basal leg, lateral amygdala, and hippocampus. In this stage, we see impaired executive functioning and decision-making, impulsivity, compulsivity, and sleep disturbance. So this is making substance use a more impulsive behavior as opposed to something where there is a decision about whether or not to use. So all of that was about substance use, but how does that relate to pain? The reward system we just described is very closely intertwined with pain because the reward system looks for how to improve our lives immediately, which includes looking for pain relief. The reward system is crucial for survival. If out of balance, it takes over, and you can wind up in a state where you're appearing impulsive or driven by immediate gratification and unable to tolerate distress. Both addictive substances and the search for pain relief can put a lot of dopamine into these circuits. Addictive substances increase activity in these neurons or prolong actions of neurotransmitters they release. Pain relief activates these neurons to drive habitual relief-seeking, and this is how we see a clear relationship between substance-seeking and pain relief. Now let's look at an example of how this may present in a patient with pain. Your back already hurts, your brain sees the couch, and predicts an opportunity for relief, sends a big dopamine signal to the nucleus accumbens area, and the nucleus accumbens area says, sounds great, go for it. And your back pain immediately feels better. Your brain recognizes that reward, and your reward circuits learn this and recognize the couch as a new context for pain relief. But in the same way with a substance use disorder, your next event lying down on the couch may not produce the same level of reward. So you seek something with a higher immediate reward, maybe taking pain medication that dumps dopamine into your system. So patients with pain and injury are going to start getting attracted to situations where they get relief. The longer you have pain, the more you will get attracted to things that give you quick relief, such as lying down, guarding, or taking medication. This means that after an injury is a really vulnerable time for people. People will start to orient towards things that give them quick relief, but not necessarily recovery. And this is unfortunately for many people an unconscious reinforcing process. So to summarize, coupled with complex social, psychological, and biological stressors, certain people can be primed for development of severe chronic complex pain and opioid use disorder. Those opioid use disorder and pain relief seeking behaviors activate and overstress the reward system. And repeated exposure to dopamine signals encourage this state. In both pain and OUD, when the reward system is overactivated, anti-reward neurotransmitters in the limbic system are enhanced, causing stress, negative affect, impulsivity, inducing compulsive behaviors to alleviate fearing lousy. In both OUD and chronic pain, the executive function of the prefrontal cortex is impaired. I'm able to exert control over ventral striatum and limbic systems, preventing activities that promote recovery. And the implication for chronic pain is that it is very closely tied to the dysregulated dopamine. So in bats, if you reduce dopamine receptors, rats will prefer opioids, have more rapid withdrawal from noxious stimuli, have more anxiety, and have greater consumption of sugar, meaning going after any reward they can find. Translating to humans, people with dysregulated dopamine systems are more likely to develop chronic pain. They are more likely to develop pain after an acute injury. And people who are activating the reward system, such as by using substances, may increase the risk of pain persisting after an initial injury. Some other implications. The brain, with an opioid use disorder, may amplify pain to justify a substance it craves. Alternating withdrawal and intoxication can physiologically drive pain, so you get sympathetic and psychomotor activation that can worsen pain. Opioid use may mask pain and then permit recurrent injury or overuse. And opioid use impairs adherence to other pain treatment plans. So as you can see, there are lots of different neurobiological processes going on in the brain that can interfere with the effective treatment of pain. Shifting gears, which of our patients with chronic pain are at most risk for developing an opioid use disorder? We know there are certain risk factors for developing opioid use disorder. Risk rates of opioid use disorder in people with chronic pain range from 8% to 12%, while problematic use ranges between 21% and 36%. The most commonly cited risk factors in the general population include younger age, higher doses of opioids, lifetime history of a substance use disorder, and mental health difficulties, including difficulties with emotion regulation and negative thinking styles related to pain. We also know there are certain patients who are more likely to be prescribed opioids, which includes people with a greater number of pain diagnoses and those with mental health and substance use disorders. So in a way, you're getting an adverse selection, meaning those who are receiving opioids are also already at an increased risk for problems like opioid use disorder. Clinicians want to help patients in pain, and they often have very few tools other than a prescription pad at their disposal. And systems-level factors can reduce access to care. Patients with mental health and substance use disorders and multiple pain problems may be more distressed, reporting more pain and more psychological symptoms. Writing an opioid prescription can be an easier alternative to other modalities that may be inaccessible or take a long time for effect. And a shortage of integrated behavioral health services in primary care and general medical settings leads to fragmented care and suboptimal care for patients with co-occurring pain, mental health, and substance use disorders. So how do we determine whether a person with pain has developed an opioid use disorder? As you can imagine, based on what we've discussed so far, it is not always clear. A lot of patients who are prescribed long-term opioid therapy who begin to develop some problems we've talked about exist in this gray zone. In this figure, you see the spectrum. On one end, physical dependence on opioids, which is a normal sequelae of being on continuous opioids. And for some folks, there are no other behaviors that raise concern. On the other end, clear opioid use disorder with compulsive use and loss of control occurs. The gray zone, however, includes some behaviors that might be indicative of problematic use or concern, but there's not necessarily clear loss of control, and that's where we get this gray zone. This can be very complex to discuss with patients, and patients may or may not agree with a clinician's conceptualization of what's going on. So here, you see two different presentations. Dependence on opioids developing through pain treatment, being using prescribed opioids, versus dependence developing through non-prescribed use of opioids. And for both presentations, a patient with an opioid use disorder will often present with social disruption, loss of control, and continued use despite harm. However, a patient with chronic pain will say that those symptoms are more related to their pain. For example, where something functioned due to pain that results in social disruption, or taking more opioids than prescribed as a response to a pain flare. As a result, patients who develop an opioid use disorder via prescribed opioids may be less receptive to an OUD diagnosis than patients who develop an opioid use disorder using non-prescribed opioids. This difficulty in attributing symptoms can be challenging for both clinicians and patients, and whether OUD is present or not, there are still similar complex underlying neurobiological processes. So in determining whether OUD is the best way to conceptualize the problems of a patient with chronic pain exhibiting opioid concerns, I think they can be helpful to reflect on the hallmark signs of a use disorder, which you can remember with the four Cs. Loss of control, compulsive use, continued use despite harms, and craving. If a person exhibits all four Cs, it is very likely that they would meet criteria for opioid use disorder. To formally diagnose opioid use disorder, the DSM-5 has 11 criteria, and if a person meets at least two of those criteria, they can be diagnosed with a mild opioid use disorder. However, if a person is prescribed opioids, two of those 11 criteria, tolerance and withdraw, cannot be counted because they're considered normal supply of continuous long-term opioid use. One problem with this exclusion is that it seems to infer that tolerance and withdrawal are not problematic if they happen while taking medication as prescribed. And while they might not be indicative of a use disorder, it is not the case that there are no adverse consequences from developing tolerance and withdrawal. Some experts have outlined the ways that OUD may present in the context of prescription opioid use, and there's a lot of different terminology that is used here since it's very much a gray zone and not well-defined. On this slide, you see some potential features of a prescription opioid use disorder. Inconsistent healthcare use patterns, such as missed appointments or lack of engagement with non-medication treatments, signs or symptoms of substance use, such as intoxication, overdose, or physical exam findings, emotional problems or psychiatric issues, use of other substances, such as alcohol, problematic medication behavior, such as escalating doses or requesting early refills, family concerns about use, functional declines, loss of parental or employment roles, and extreme difficulty even with a slow opioid taper. So when a patient presents with a consistent pattern of these behaviors, or if those behaviors are quite severe, then prescription opioid use disorder may be present. To think about the behaviors we're looking for in a different way, you can look at this yellow to red flag spectrum of different types of behaviors. The yellow flags are things that may or may not raise concern for opioid use disorder, and as you move down the list, the red flags are things that are much more likely to be associated with opioid use disorder. People who report that they've lost their medications or they've been stolen on a repeated basis may be having significant misuse problems or a use disorder. On the other hand, people who request an increased dose of opioids may have inadequate treatment of their pain for a number of different reasons. So what is the best way to handle this in primary care? Having pain, taking opioids, and having a substance use disorder can all be very stigmatizing. So one approach is to normalize the evaluation of an opioid use disorder as part of universal precautions. Discuss this evaluation during informed consent before you start prescribing an opioid and validate the fear and stigma that patients report to you. Saying things like, I ask all of my patients these questions, or I have all of my patients do urine drug testing and pill counts. I want to make sure that none of my patients are being harmed by this medication, so we do these things to make sure your treatment is both safe and effective. To do an initial evaluation of opioid use disorder for a patient with chronic pain, you have to start with also evaluating their pain. Here you can see we've outlined some of the pain-focused parts of the evaluation. Evaluate the chronic pain condition and pain-related function. Is there already a diagnosis, or is a diagnosis possible? Would further evaluation prove beneficial? What is the response to pain medication? In the absence of functional improvements, the patient may be experiencing therapeutic failure of opioids. If there is no functional benefit, then there is a lack of opioid benefit. So why would opioids be continued? You can review past treatment trials. Are there non-opioid medications that could be optimized? Other non-medication options that could be trialed? What were the results of previous non-opioid treatment trials? If there is resistance to any non-opioid treatment options, where is that resistance coming from? Next, you will want to consider some of the risk factors for OUD we previously discussed, as well as other biopsychosocial contributors to both pain and opioid use disorder. What side effects are present? What is the patient's relationship with health care providers? Are there concerning behaviors? What is the prescription history? Have there been lost or stolen medications, frequent ED visits, or concerning reports from family members? What is the patient's history of substance use, as well as their current substance use? And what other psychosocial factors are contributing to the patient's presentation, such as mental health concerns, thought patterns, or stressors? You may consider measures of depression, anxiety, pain-related worry, or pain self-efficacy to help clarify the psychosocial factors contributing to the pain. Oftentimes, it's not immediately clear whether OUD is present and ongoing monitoring is necessary. Diagnostically, you may consider urine drug tests, pill counts, and the use of a prescription drug monitoring system. Urine drug testing can also include the evaluation of alcohol use, and we do have a lecture about urine drug testing that I encourage you to review. You can also use review of other medical records, case consultation, and, when possible, using a multidisciplinary approach. There are several published questionnaires and tools that can help with the assessment of opioid-related concerns. However, none of them can definitively diagnose opioid use disorder. I'll mention two here. The Prescribed Opioids Difficulty Scale, or PODS, identifies common difficulties that a patient ascribed to chronic opioid therapy and can provide a framework for a patient-centered clinical dialogue about opioid medications. It's a useful tool for understanding difficulties that, again, cannot diagnose OUD. The Opioid Risk Tool, or ORT, is another validated tool that predicts risk of future opioid misuse based on some of the risk factors we've reviewed earlier. So how do we go about diagnosing OUD? There is not one test or questionnaire that can confirm prescription opioid use disorder. An initial PCP evaluation provides more of a basis for a risk and benefit determination, but someone with low benefit or high risk does not necessarily have OUD. This initial evaluation will place the focus not only on concerning behaviors but also on pain and pain care and can help the clinician highlight the concerning behaviors while also discussing optimal pain treatment. It is important to underscore that a person can have both pain and OUD. It is not an either-or. Given the long history of under-treatment of pain in the healthcare system, our default stance should be to believe that a person reporting pain does, in fact, have pain and that their pain needs to be treated, irrespective of what other conditions they may also have. However, treating pain with opioids in the setting of opioid use disorder is risky. If, based on your initial evaluation, you're not sure whether a person has OUD or not, or you don't feel comfortable making that diagnosis, it may be valuable to consider referral to a specialist to further evaluate. Ultimately, the diagnosis of opioid use disorder is made using the DSM-5 criteria, and the gold standard for determining if people meet those criteria is a clinical interview. As we've discussed, it's often the case that people fall into this gray zone, or it is unclear if opioid use disorder is present, and the lack of diagnostic clarity represents significant challenges for both patients and clinicians. To address the scenario where harms outweigh benefits, but tapering does not go well, some have proposed creating a new diagnostic entity. There is not widespread consensus on this topic, but it is an emerging area of research to continue watching. Ultimately, the question you are asking is, is this treatment beneficial? What are the risks and benefits of this treatment? So it can be helpful to orient around an assessment of the treatment rather than a judgment of the person. Whether OUD is present or not, if the harms of continued opioid use appear to outweigh the benefits, you should work with the patient via a patient-centered conversation to taper the opioids and continue to treat the pain with non-opioid treatments and other modalities of treatments. Importantly, abrupt discontinuation, rapid tapering, or a tapering without patient consent are all associated with severe adverse outcomes and are not recommended. Approaching this process in a supportive patient-centered manner is recommended. If OUD is present, a change in treatment plan is likely necessary, but it's important to connect a person to evidence-based opioid use disorder treatment. For patients with pain in OUD, there are two good treatment choices, methadone and buprenorphine. Methadone is a full agonist opioid that typically provides analgesia for four to six hours. Currently, it is only legally dispensed through a federally qualified opioid treatment program for treatment for OUD. Buprenorphine is a partial agonist that typically provides analgesia for four to six hours, but it can be dosed BID or TID for improved pain management. Buprenorphine is increasingly used as an alternative to full agonist opioids and can be used for both pain and OUD. Office-based prescribing of buprenorphine can be done with a standard DEA registration number that includes Schedule III authority. Finally, although maltrexone is also an approved medication for OUD, there isn't really data to support its use for pain, which is why it's not included on this slide. So returning to our case, recall that our first case, we had a 35-year-old female with migraines and diffuse myofascial pain. The patient had been prescribed opioids for five years, had experiences of severe depression and anxiety and chronic nausea, had a history of adverse childhood experiences, and was struggling to provide care for her children. She was also prescribed a high-dose benzodiazepine. She had a history of losing opioid prescriptions, obtaining opioids from multiple providers, and reported allergic reactions to non-opioid pain medications, missing appointments, and frequently asking for dose increases, which are several of the yellow and red five behaviors we reviewed earlier. So does she have pain? Yes. She has multiple pain-related diagnoses. Does she have an opioid use disorder? Also yes. She has trouble with will obligations and has given up or reduced activities regarding taking care of her children and also has evidence of compulsive and potentially hazardous use. What factors placed her at risk for development of an opioid use disorder? Including young age at opioid initiation, concomitant use of benzodiazepines, depression and anxiety, which increase vulnerability for substance use, and negative childhood impacts that may have impacted brain development and coping strategies. She also had a history of medication non-adherence, including Ross prescriptions and possibly compulsive use of medication, as well as possible frequent bouts of opioid withdrawal from overuse of opioids causing negative affect, motivation, and craving. So what can we do to help this patient? Identifying underlying biopsychosocial factors that are contributing to pain, support a multidisciplinary approach to treatment, identify neural processes that may be contributing to behavior, guide the patient towards activities and treatment modalities that increase natural reward, such as limiting substance use and social reinforcement, problem solving, effective emotional coping, small goal achievement, and quality of life activities, offer safe and effective treatment for pain and opioid use disorder, and coordinate care with her psychiatrist to optimize her mental health treatment. Our patient undergoes a full opioid use disorder assessment and is determined to have a moderate opioid use disorder based on failure to fulfill roles, continued use despite harms, time spent procuring medication, and craving. She's reluctant and scared to consider alternative treatments or seek opioid use disorder treatment. But she's appreciative of the honest assessment of her condition. She said she'd like to think about the idea. Two weeks later, she makes an appointment to see you and seeks OUD treatment. Three months after stabilizing and starting on buprenorphine naloxone, along with cognitive behavioral therapy, she says, thank you so much for helping me. I am myself again. I'm finally enjoying life with my kids, and I'm starting to think about starting a small business. In this case, I want to highlight that a supportive, patient-centered, honest feedback to this patient was an integral part of getting her into evidence-based treatment for opioid use disorder. If we think back to case two, we had our 62-year-old male with multiple sites of pain on high-dose opioids escalated by his prescriber over the course of 20 years. And he presented with very few yellow or red flag behaviors. He had two early refills over the course of six years and no other aberrancies. However, he has very poor function and moderate to severe pain interfering in multiple areas of his life. So does this patient have pain? Yes, clearly. Does this patient have an opioid use disorder? No, not from our assessment. While he is unable to fulfill well obligations and does report interpersonal problems, he attributes this to pain, and there's limited evidence to the contrary. The DSM-5 criteria of withdrawal or physical dependence and tolerance do not apply since he's prescribed opioids. And his dose was escalated by his prescriber. There was no self-escalation and limited evidence of misuse behaviors. So it would be difficult to conclude that he had any loss of control, one of the four Cs. But does this person have opioid dependence or complex persistent opioid dependence? Perhaps. What are the benefits of continued opioid therapy for this patient? The patient believes that there is benefit present, but there's limited data to support this. What are the harms of continued opioid therapy? He has poor pain-related function, side effects, and he's at an increased risk for respiratory problems. So what can you do to help this patient? You can offer evidence-based non-opioid pain treatments and work closely with the patient to modify the opioid treatment regimen. In this case, the patient undergoes a full opioid use disorder assessment and does not meet criteria for opioid use disorder. You discussed that while opioid use disorder is not present, the harms of continued opioid use appear to outweigh the benefits. We suggest an opioid taper or a rotation to buprenorphine, as well as other enhancements to their pain care plan. The patient is reluctant to consider a change and is afraid of worsening pain, but ultimately chooses a rotation to buprenorphine and accepts a referral to physical therapy. He also accepts a referral to the sleep clinic to evaluate his snoring. Three months after stabilizing on buprenorphine and attending physical therapy, the patient reports that he's more active and that his pain has not gotten any worse. So, in conclusion, chronic pain and opioid use disorder share many common features that can motivate a person's behaviors. Diagnosing opioid use disorder during pain treatment can be complex and requires a thorough evaluation. Typical substance use disorder risk factors probably apply to prescription opioid use disorder as well. And we know that higher risk groups are those who are younger, using substances, using higher doses of opioids, or having mental health comorbidities. Opioid use disorder has a high risk for mortality if untreated, so we need to treat or refer individuals with OUD to treatment, where we also treat their pain. Our references are listed here, along with some information about the PCSS MOUD mentoring program and discussion forum, as well as additional information about PCSS. Thank you so much for attending, and have a great day.

Opioid Use Disorder

Chronic Pain

Neurobiological Framework

Patient Evaluation

Opioid Risk Tool

Non-opioid Treatments

Patient-centered Approach