Chapter 10: Pain Management in Opioid Use Disorder (OUD)

Welcome to Last Minute Lecture.

This free chapter overview is designed to help students review and understand key concepts.

These summaries supplement, not replace the original textbook and may not be redistributed or resold.

For complete coverage, always consult the official text.

Welcome back to the Deep Dive.

Today, we're tackling something really tough, a real tightrope walk in clinical practice.

Yeah, what's up?

Managing significant pain in patients who are also dealing with opioid use disorder or OUD.

Yes, that is incredibly challenging.

It's scale, it's just huge.

We're talking millions of people diagnosed back in 2018 alone.

And here's the really difficult part.

The number one reason people start misusing opioids,

it's often seeking relief from pain.

Exactly, it puts clinicians in a bind right away.

First, we absolutely have to treat the pain, treat it effectively, but without adding to the stigma the patient already faces.

And second, there are these two kind of opposing forces happening physiologically.

These patients, they often build up a really high tolerance to opioids, so they need more medication for the same effect.

Right, tolerance.

But at the same time, they frequently develop increased pain sensitivity, we call it hyperalgesia.

Their nervous system basically starts amplifying pain signals.

Wow, so higher tolerance and more sensitivity to pain.

Precisely, it's a very difficult combination.

That really makes standard pain protocols almost useless, doesn't it?

It complicates things immensely.

So okay, our mission for this Deem Dive is pretty clear then.

We need to figure out how to properly screen and assess these patients.

Yeah, assessment is key.

And then, how do we build a treatment plan that actually relieves their pain, but also crucially prevents relapse?

A plan that does both.

And finally, how do we monitor these powerful drugs we use to make sure they're safe and working?

And the main tools we're looking at here, according to our sources, fall under medication -assisted treatment, AFTU.

Right.

We're focusing primarily on buprenorphine and methadone.

They're effective because they act on that Muth opioid receptor.

Okay.

And they do two things at once.

They provide pain relief, the analgesia, and they help reduce those intense physiological cravings that drive the addiction.

Got it, so tackling both the pain and the craving.

Exactly, and to really get why this is so complex, you have to understand the basics, like the link between using opioids long -term and how it changes pain signaling.

No deception.

Okay.

Chronic opioid use, it actually changes how the central nervous system processes pain.

It rewires things, essentially.

And that leads to that combination you mentioned.

Yes, that difficult mix of needing more drug, the tolerance, and feeling more pain, the hyperalgesia.

And it's not just physical pain signals, is it?

Addiction involves the brain's reward system pretty heavily.

Oh, absolutely.

It's deeply tied into the mesolimic pathway, the brain's reward circuit.

You get this powerful reinforcement cycle.

How does that work?

Well, initially, opioids trigger dopamine release, that feeling of pleasure or euphoria.

That's positive reinforcement.

Okay, the high.

Right, but then when the person starts to withdraw, they feel awful, intense distress, dysphoria.

So taking more opioids relieves that awful feeling.

That's negative reinforcement.

They're using just to feel normal, or rather to stop feeling terrible.

So it hooks them in two ways.

Exactly, and when this cycle is layered on top of real chronic physical pain, you can see how it drives using more and more more often.

Okay, that makes sense.

Let's shift to assessment then, before we even think about prescribing what's involved in a good workup.

It has to be detailed.

You need to screen for other issues, like depression or anxiety, which often go hand in hand with OUD and chronic pain.

Like comorbidities.

And a really thorough medication review, everything.

Prescriptions, OTC stuff, even herbal supplements.

You have to know what they're taking to avoid dangerous interactions.

Good point, herbal supplements too.

Definitely.

And of course you need to find out their MAT status.

Are they currently on it?

Have they been in the past?

And are there specific tools we should use?

Yes, we have structured tools to help assess risk and guide treatment.

For patients starting opioids for chronic pain, things like the Opioid Risk Tool, the ORT, it helps predict the chances of future problems.

We also lean heavily on objective monitoring.

The big one is the Prescription Drug Monitoring Program,

or PDMP.

The state database.

Exactly, it's electronic, tracks -controlled substance prescriptions.

It helps us spot potential red flags,

filling prescriptions too early, getting large amounts using multiple doctors or pharmacies.

That sounds really useful, but I think there was a catch with it, something it might miss.

Yes, absolutely.

A really important caveat,

methadone that's dispensed from those federally regulated opioid treatment programs,

the methadone clinics,

that dosing information might not show up in the PDMP report.

So the record might look clean, even if they're getting methadone daily from a clinic.

Precisely.

Clinicians have to be aware of that potential gap.

You might need to coordinate directly with the clinic.

Okay, good to know.

And what about urine drug screens?

When do they come in?

They're another key part of monitoring, but you need to understand the different types.

Go on.

The initial screen is usually an immunoassay.

It's fast, it's cheap, but it's known for false positives and false negatives.

For instance, we know ketchupine, an antipsychotic, can sometimes trigger a false positive for fentanyl.

Wow, okay, so not perfectly reliable.

Not for definitive answers.

If you get an unexpected result on that initial screen or something just doesn't add up with the clinical picture, you absolutely must get it confirmed.

Confirmed how?

With the gold standard test.

Gas chromatography, mass spectrometry, GCMS.

GCMS.

It's much more precise.

It identifies the specific chemical compounds present so you know exactly what the patient has taken.

No ambiguity.

Okay, so screen first, but confirm with GCMS if anything looks off.

Makes sense.

Now, when we actually start drug therapy for pain in someone with OUD,

what are we trying to achieve?

What are the goals?

There are really five main goals we're targeting.

One, obviously reduce the pain, treat the underlying injury if there is one.

Two, reduce those cravings.

Three, prevent relapse back into misuse.

Makes sense.

Four, manage any side effects from the medications, and five, ultimately improve their overall quality of life and function.

And we mentioned buprenorphine and methadone are the main players.

What about naltrexone?

Right, naltrexone is different.

It's a pure opioid antagonist.

It blocks the effects of opioids.

So it wouldn't help with pain.

Exactly, it works against active pain management, so it's generally not used when the primary goal is treating ongoing significant pain alongside OUD.

Got it.

Let's dive into buprenorphine then.

You said it's a cornerstone.

Why is it so important?

Its mechanism of action is key.

It's a partial agonist at the mu opioid receptor.

Partial agonist, what does that mean practically?

It means it activates the receptor, but not fully.

This leads to its biggest safety feature, the sealing effect.

Sealing effect.

Yeah, unlike full agonists like morphine or methadone, once you reach a certain dose of buprenorphine, taking more does not produce significantly more euphoria or, crucially, more respiratory depression.

Ah, so there's a built -in safety limit on the breathing suppression risk.

Exactly, and makes it much safer in terms of overdose risk compared to full agonists.

That's definitely reassuring.

But, if it has a sealing, how well does it actually work for really bad pain, like after surgery?

It can be effective, but it's, well, it's complex.

Buprenorphine might also act at another receptor, the opioid receptor like one, or ORL one, and that action might help counteract that hyperalgesia, the increased pain sensitivity we talked about, so it can help normalize pain perception.

Interesting, but you said initiating it is complex.

Extremely, you have to be incredibly careful, because buprenorphine has a very high binding affinity for the mu receptor.

It binds really tightly.

Okay, so it sticks well.

Why is that a problem?

If the patient has recently used a full opioid, like heroin or fentanyl, or even prescribed oxycodone, and still has significant levels in their system,

buprenorphine will basically kick those full opioids off the receptors and bind itself there instead.

Because it's only a partial agonist, this sudden shift causes immediate and often severe withdrawal symptoms.

We call it precipitated withdrawal.

Ouch, that sounds terrible.

How do we avoid that?

We have to wait until the patient is showing clear objective signs of opioid withdrawal before giving the first dose.

We use a standardized tool for this.

What's the tool?

It's called the Clinical Opiate Withdrawal Scale, or CIWS.

It helps us objectively measure things like pulse rate, sweating, pupil size, anxiety levels, muscle aches.

You need a certain score on the CIWS scale to confirm they're sufficiently in withdrawal before safely starting buprenorphine.

Okay, CIWS scale, crucial step.

Now, I remember reading something about interactions specifically with metabolism,

CYP enzymes.

Yes, that's really important clinically.

Buprenorphine is highly bound to proteins in the blood, and it's mainly metabolized by the CYP3A4 enzyme system in the liver.

CYP3A4, okay.

This means other drugs or even supplements that affect CYP3A4 activity can change buprenorphine levels.

Can you give an example?

Sure.

Think about St.

John's wort.

It's a common herbal supplement people take for mood.

Right.

St.

John's wort is a potent inducer of CYP3A4.

It speeds up the enzyme.

So it would chew up the buprenorphine faster.

Exactly.

It decreases the concentration and effectiveness of buprenorphine.

This could lead to withdrawal symptoms, increased cravings, breakthrough pain, and potentially relapse.

So asking about supplements is vital.

Wow, okay.

That's a great clinical pearl.

Now let's talk dosing.

Is the dose for OUD maintenance the same as the dose for pain?

This is another critical difference.

For OUD maintenance, buprenorphine is typically dosed once a day.

That works well for controlling cravings and preventing withdrawal over 24 hours.

Okay, once daily for OUD.

But it's pain relieving effect, the analgesia, it wears off much faster.

It only lasts about six to eight hours.

Only six to eight hours for pain relief.

Right.

So if you're using buprenorphine to treat both OUD and significant pain,

that once daily dose isn't enough for pain control throughout the day.

So what do you do?

You have to divide the total daily dose and give it more frequently.

Typically two or three times a day, say every six to eight hours, to maintain consistent analgesia.

That's a big change for the patient and the prescriber to manage.

It is, and it requires clear communication.

And buprenorphine comes in lots of forms, right?

Films, patches, even implants.

Yes, a variety of formulations.

Sublingual films or tablets, buccal films that dissolve in the cheek, transdermal patches, even long acting injections and implants.

Are they interchangeable?

Like can you easily switch from a film to a patch at the same dose?

Absolutely not.

This is crucial.

The bioavailability of how much drug actually gets absorbed into the bloodstream varies wildly between formulations.

How different are we talking?

Well, the sources mentioned buccal films might be around 55 % bioavailable.

The common sublingual formulations, like suboxone film, maybe 35%.

And the transdermal patch, only about 15%.

Wow, huge differences.

Huge.

And there aren't reliable, standardized conversion charts.

So switching formulations is risky, if not done very carefully, often requiring dose adjustments and close monitoring.

You could easily underdose or overdose someone.

Okay, not interchangeable, got it.

What about the naloxone that's often combined with buprenorphine, like in suboxone, what's its purpose?

The naloxone is purely there as an abuse deterrent.

How does it deter abuse?

When you take the combination product correctly, letting it dissolve under the tongue or in the cheek,

the buprenorphine is well absorbed, but the naloxone absorption is very poor.

It basically doesn't have an effect.

But if someone tries to misuse the product by dissolving and injecting it, then the naloxone is fully absorbed and naloxone is an opioid blocker.

It would counteract the buprenorphine's effects and could potentially precipitate withdrawal, making injection unpleasant and pointless.

Clever, so it only becomes active if misused by injection.

Correct, and remember the prescribing rules quickly.

Right, different rules, depending on why you're prescribing it.

Yes, if it's purely for pain relief, for analgesia, any prescriber with DEA registration can write for it.

Okay.

But if it's being used to treat OUD, the prescriber needs a special waiver, often called a data waiver or X waiver, linked to their DEA number.

And there used to be limits on the number of patients they could treat, though those have changed recently.

Okay, good distinction.

Let's switch gears now from buprenorphine, the partial agonist with the ceiling effect, to methadone.

All right, methadone.

This one's a full opioid agonist, right?

Very potent for pain, which explains why it's a schedule two drug.

Exactly, methadone is a real powerhouse for pain control.

And its mechanism is interesting too.

It's a full methyl agonist, yes, but it also does something else.

What's that?

It acts as an antagonist at the NMDA receptor, N -methyldeaspartate.

NMDA antagonist.

What does that do?

That NMDA action is thought to help stabilize the nervous system,

maybe reduce the development of tolerance over time compared to other full opioids.

It might also help with certain types of neuropathic pain.

Interesting.

And methadone also has those two different ways it gets dispensed, right?

Yes, depending on the indication.

If it's prescribed for pain, it usually comes as tablets and the patient fills the prescription at a regular retail pharmacy.

Okay, standard pharmacy for pain.

But if it's for OUD maintenance treatment, it's typically a liquid formulation, dosed once daily and dispensed only through those federally regulated opioid treatment programs, the methadone clinics.

Patients usually have to go there daily, at least initially.

Very different systems.

Now, since methadone is a full agonist and doesn't have that safety ceiling like buprenorphine, what's the biggest risk we need to monitor for?

Respiratory depression is always a risk with any full agonist, especially if the dose is too high or increased too quickly.

But the unique and perhaps most critical monitoring requirement for methadone relates to the heart.

The heart?

Yes, methadone has a notoriously long and highly variable half -life.

It can range anywhere from eight hours to maybe 59 hours or even longer in some people.

Wow, that's a huge range.

It is.

And it's metabolized by several different CYP enzymes, making interactions common.

But the big cardiac issue is that methadone carries a black box warning because it can prolong the QTC interval on an electrocardiogram, EKG.

QTC prolongation.

Why is that dangerous?

A significantly prolonged QTC interval increases the risk of a potentially fatal cardiac arrhythmia called torsades to point.

Torsades.

Okay, that sounds serious.

It is very serious.

So EKG monitoring is absolutely mandatory.

How often?

You need a baseline EKG before starting and then another one within 30 days after initiation or significant dose increases and then at least annually after that.

Baseline 30 days annually.

Got it.

You also need to monitor electrolytes, specifically potassium and magnesium because low levels can worsen the QTC prolongation risk.

They need to be in the normal range.

And what if the QTC gets too long?

Is there a cutoff?

Yes.

If the QTC interval goes above 500 milliseconds, that's generally considered a hard stop.

You typically need to reduce the dose or discontinue the methadone altogether or at least consult with cardiology.

Okay, QTC over 500 meters is the danger zone.

That's critical to remember.

And just like duprenorphine, is the dosing schedule for pain different from OUD maintenance?

Yes, same principle applies.

Even though the OUD maintenance dose is given once daily because of the long half -life for preventing withdrawal.

The pain relieving effect, the analgesia doesn't last nearly as long, maybe six to eight hours, similar to buprenorphine's analgesic duration.

So again, you need to split the dose for pain control.

Correct.

For effective pain management, the total daily methadone dose needs to be divided and given maybe three or even four times a day.

And one more complexity with methadone.

Converting patients between methadone and other opioids is really tricky.

Cross -tolerance isn't complete or predictable.

It requires very careful calculations and close monitoring.

Right, sounds like methadone is very effective that comes with significant complexities and risks.

That's a good summary.

High efficacy, but high risk if not managed properly.

So given all these challenges with buprenorphine and methadone, if a patient with OUD has only mild or moderate pain, what should be our first approach?

Are we just reaching for Tylenol?

Non -opioid strategies are absolutely the first line.

And yes, simple analgesics like acetaminophen Tylenol and NSAIDs like ibuprofen or naproxen are excellent starting points.

Why are they preferred?

Because they work through different mechanisms.

They don't touch those more opioid receptors so they don't carry the risk of triggering cravings or contributing to misuse patterns.

Okay, makes sense.

Avoided the mu receptor if possible.

What about for chronic pain?

For chronic pain, we rely heavily on what we call coanalgesics or adjunctive agents.

These are medications from other classes that can help manage pain, especially neuropathic or centralized pain.

Like what?

Things like certain antidepressants, TCAs or SNRIs, some anti -convulsants like gabapentin or pregabalin, and sometimes skeletal muscle relaxers, although cautiously.

These can help calm down an overactive nervous system.

Okay, adjunctive agents are key.

Now I remember the source material specifically warned against one particular medication that sometimes gets used for pain, sort of opioid -like.

Ah, you're probably thinking of tramadol.

That's the one.

Why is it generally avoided here?

Tramadol is generally not recommended for patients with OED, even though it's often considered a weaker opioid, it does have activity at the mu opioid receptor.

Enough to be a problem.

Enough that it can potentially trigger cravings, reinforce drug -seeking behavior, and lead to misuse in this vulnerable population.

So the risk usually outweighs any potential benefit.

Okay, SkiR clear of tramadol.

What about using actual full opioids like oxycodone or morphine for these patients?

Is that ever okay?

It's generally reserved for very specific situations like severe acute pain,

think major surgery or trauma, or maybe cancer -related pain.

And even then with precautions.

Absolutely.

It has to be in a very controlled setting, ideally using abuse deterrent formulations if available.

And you have to anticipate that because of their existing tolerance, these patients will likely need higher doses and possibly shorter dosing intervals than someone without OUD.

Close monitoring is paramount.

Reserved for rare, severe cases with lots of oversight.

Now beyond medications, what else is in our toolkit?

The non -drug approaches.

Oh, non -pharmacologic strategies are essential.

You really need a multimodal approach for any chance of success.

What kinds of things work?

Cognitive behavioral therapy, CBT, is often very effective.

It helps patients change how they think about their pain, develop better coping strategies, and address those maladaptive thoughts that can worsen suffering.

Changing the thinking patterns, okay.

And then there are other physical and complementary therapies.

Things like acupuncture, massage therapy, meditation or mindfulness practices, and 10 -NS units transcutaneous electrical nerve stimulation.

So a whole range of options to combine with medication.

Definitely, it's rarely just about the pills.

Okay, let's talk about a really tricky scenario, surgery.

What happens when a patient who is stable on buprenorphine needs an operation and will have significant post -op pain?

Yeah, that's one of the most complex clinical situations.

And honestly, there aren't universally agreed upon guidelines.

Buprenorphine's high affinity for the mu receptor creates that blockade, making it hard for standard post -op opioids to work effectively.

So what are the options?

The sources suggested a few approaches.

Right, the chapter outlines sort of three main potential strategies.

Okay, what's the first one?

Option one is to continue the patient's regular buprenorphine maintenance dose right through the surgery.

Then for the acute post -op pain, you use a short -acting high affinity full opioid, something like fentanyl or hydromorphone.

And you just give higher doses?

Essentially, yes.

You have to titrate to effect, expecting that you'll need higher than usual doses to overcome buprenorphine's blockade at the receptor and achieve pain relief.

It requires very careful monitoring.

Okay, continue buprenorphine, add high affinity opioid.

What's option two?

Option two leverages buprenorphine's own analgesic properties.

You take the patient's total daily maintenance dose of buprenorphine, but instead of giving it once a day, you divide it and administer it every six to eight hours.

Ah, using the buprenorphine itself for the pain by dosing it more frequently.

Exactly, trying to maximize its shorter analgesic effect.

This might work for moderate pain levels.

Yeah, and the third option.

The third option, which is probably more common for planned surgeries, involves temporarily stopping or significantly reducing the buprenorphine dose a few days before the procedure.

Stopping buprenorphine, then what?

Then you initiate standard full opioid agonists for perioperative pain management.

The challenge here is intense monitoring, especially for respiratory depression, as the buprenorphine clears the system and the receptors become fully available to the new opioids.

And you have to plan carefully for restarting the buprenorphine after the acute pain phase.

Wow, okay, three very different strategies, each with its own challenges.

Needs careful consideration for each patient.

Absolutely, it requires coordination between the surgeon, anesthesia, and the patient's OUD treatment provider.

Let's touch quickly on special populations.

What about kids or adolescents?

Well, the formal safety and efficacy data for buprenorphine in those under 16 or methadone under 18 is limited.

They weren't studied extensively in those age groups initially, but for adolescents with severe OUD, expert consensus and guidelines generally do recommend considering that, often buprenorphine, because the risks of untreated OUD are so high, it's a risk benefit calculation.

Okay, what about older adults, geriatric patients?

Extra caution needed there, start low, go slow is the mantra.

Older adults often have reduced liver, kidney, and heart function, making them more sensitive to medication effects and side effects.

And more likely to be on other medications too, right?

Exactly, the risk of drug interactions is much higher, so careful dose selection, slow titration, and very close monitoring are essential.

And pregnancy,

can women on MAT continue during pregnancy?

Yes, both methadone and buprenorphine, specifically the formulations without naloxone are considered the standard of care for pregnant women with OUD.

Untreated OUD poses significant risks to both the mother and the fetus.

Are they safe for the baby?

Both medications do cross the placenta, and the baby can be born physically dependent, experiencing neonatal abstinence syndrome, or NAS.

However, treatment with methadone or buprenorphine stabilizes the mother, reduces illicit drug use, and improves prenatal care access, which generally leads to better outcomes than untreated addiction.

Is one preferred over the other in pregnancy?

Some studies suggest that buprenorphine might be associated with less severe NAS compared to methadone, potentially requiring shorter hospital stays for the infant.

But both are considered safe and effective options.

Good to know, and do doses need changing during pregnancy?

Often, yes.

Pregnancy causes significant physiological changes, including changes in how drugs are metabolized and distributed.

Many women require dose increases, sometimes substantial ones, especially in the third trimester, to maintain effectiveness.

Okay, dose adjustments likely needed.

Finally, with such a complex treatment plan involving MAT, pain control, maybe adjunctive meds, how do we track if it's actually working?

How do we monitor progress?

We need a systematic way to check in.

The chapter mentions a useful framework, often called the 5As of analgesia monitoring.

The 5As, okay, what are they?

First is analgesia.

Simply, how well is the pain controlled?

Using pain scales, asking about relief.

Makes sense, a number one.

Second is adverse reactions.

Are they experiencing side effects?

Common things like constipation, nausea, sedation, need monitoring and management.

Okay, side effects, that's two.

Third is aberrant behaviors.

Are there any signs of medication misuse?

Things like asking for early refills, losing prescriptions, using illicit substances, getting drugs from others.

Watching for misuse signals, three.

Fourth is activity or activities of daily living.

Has the patient's function improved?

Are they able to do more work, socialize, take care of themselves?

That's a key goal.

Function, number four.

And fifth is effect.

How is the pain and the treatment impacting their mood and mental health?

Assessing for depression, anxiety, overall well -being.

Mood and mental state, got it.

Analgesia, adverse reactions, aberrant behaviors, activity, effect.

The five A's, that's a really helpful framework.

It provides a structured way to evaluate the overall effectiveness and safety of the pain plan beyond just the pain score.

So pulling this all together, what's the big clinical takeaway for someone managing pain in an OUD patient?

I think the most crucial point is that non -opioid medications and strategies are always your first line for mild to moderate pain.

You want to avoid opioids if possible.

But when you do need to use the MAD agents themselves, buprenorphine or methadone for concurrent pain management,

remember that the standard once daily OUD maintenance dosing is not enough for pain control.

The key dosing point.

Yes, you absolutely must divide the total daily dose and give it two, three, maybe even four times a day to cover that shorter duration of analgesic effect.

Critical difference.

And this all hinges on really intensive patient education.

What specifically do patients need to know?

They need crystal clear instructions on how to take the medication correctly, especially if the dosing schedule is complex.

They need to know what side effects to watch for and report.

And crucially, given the ongoing risks, every patient receiving opioid therapy, including Matt, should be strongly encouraged to have naloxone, the opioid reversal agent available in their household.

Naloxone rescue kits.

Exactly.

And not just had it, but make sure family members or housemates know where it is and how to use it in an emergency.

That education piece is vital.

Absolutely vital.

This has been incredibly helpful in navigating such a complex area.

Here's a final thought maybe for you, the listener, to reflect on as you integrate all this.

Thinking about buprenorphine with its partial agonism and ceiling effect safety versus methadone, the full agonist with its potency, but also that QTC risk.

Can you picture a specific clinical scenario?

Maybe an older patient, lots of heart issues, but severe chronic pain.

What factors in that scenario would really push you towards recommending one agent over the other, trying to balance that tightrope of pain control,

managing risks and preventing relapse?

That's the kind of critical thinking these situations demand every day.

An essential question.

Definitely something that you want.

Thanks so much for diving deep with us today.

My pleasure.

We'll catch you on the next deep dive.