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Presentation: Pain - rethinking our approach to pain and the role of opioid therapy

Codeine up-scheduling workshop, Melbourne, 28 November 2017

16 January 2018

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  • Presented by: Dr Malcolm Hogg, Royal Melbourne Hospital and Head of Pain Services, Melbourne Health
  • Presented at: TGA workshop: Codeine up-scheduling, 28 November 2017
  • Presentation summary: This presentation provides an overview of current approaches to pain management.


Pain - rethinking our approach to pain and the role of opioid therapy

Malcolm Hogg
Royal Melbourne Hospital and Head of Pain Services
Melbourne Health

TGA workshop: Codeine up-scheduling, 28 November 2017

Look, I'm delighted to introduce Malcolm Hogg who's here at Royal Melbourne Hospital as a staff specialist in anaesthesia and pain management. I mean so often those disciplines of anesthesia and pain management quite logically go together, but of course, pain management extends much more broadly into the community rather than while you're in theatre.

Dr. Hogg supervises a coordinated range of services, so both acute services and interventional pain management in a hospital situation, as well as outpatient services, and therefore, Malcolm's experience, both in working with cancer and non-cancer pain, I think, is tremendously useful as well as the broader allied health pain management programs. Malcolm is also a very active researcher in trying to understand people who transition, I guess sadly, from acute pain to developing chronic disabling pain, and sometimes opiates can actually be a cause. rather than a remedy for that. Also important that Malcolm is past president of the Australian Pain Society, and on the board of Pain Australia, coordinating the Waiting in Pain Project, a systematic investigation into provision of persistent pain services in Australia.  I think the services are for persistent pain, not their services being persistent.

Anyway, it's fantastic to have Malcolm and he's going to specifically focus on the role of opioids at large, and I'll probably touch on I imagine the Schedule 8 opioids, the strong opioids as well as the role of weaker opioids like codeine, and particularly looking at their role in chronic non-cancer pain, as well as where they are used for acute pain or cancer pain. So, thanks again. Malcolm

Thank you, John, I'm conscious of time so I'm going to run through some of these slides, and some of it is sort of a science background, but I'm really pushing the concepts behind the theories and the evidence in the literature.

I do a number of things for pharmaceutical companies including Mundipharma, primary producer of strong opioids as well as some consultancy work. I haven't got there but I've been a 25-year member of Essendon Football Club but have not been on their pharmaceutical Advisory Committee. I think in some ways, one of the drugs that they were on has now been approved by the TGA in America for use in older people. So, Steven Dank may well just have a comeback.

So, the take home message is that pain is multi-dimensional, and that there's actually a neurological basis for this. So, we consume when we see chronic pain although GPs and pharmacists think, well there's all these psychosocial factors there of someone with pain, but that has got a neurological basis and I want to talk through that quite extensively, and how that should be incorporated into our assessment and management program.

Opioids are antinociceptive and we forget this. There's a real push at the moment from my colleagues and the faculty of pain medicine and RACGP etc say opioids have no role in chronic pain. They should be clarified. Opioids are antinociceptive and we need to learn to use them better. And there's a side effect or a potential of misuse and dependence which is also an issue in the community. So, we need a better broader understanding of how we're going to use opioids to maximize their benefit and minimize the risk, both at a society level and a personal level. And we need to recognize that acute surgical management is highly dependent on opiates.

Some of the major advances in healthcare, including so  bypass surgery, cutting open your sternum requires high dose opiates in order for your heart to tolerate that. And so, it's been very useful in an anaesthetic sense to understand that, but transitioning into chronic pain, it's much harder to get that sort of benefit or maintain that benefit, and therefore optimal use of opioids in the pain setting requires a lot of effort. And possibly this is where we've fallen down is that we haven't quite recognized them. We set and forget and let them go and certain groups have got into trouble or there's being been society harm.

So, that's sort of the take-home message. I'm going to lead on to a few comments about what resources are available and some comments about a local monitoring system in Victoria which is going to be trialled in 2018.

So, this is my approach to pain. We've changed our approach to pain somewhat, so clinically, we think about who is the person, what are the mechanisms in this person's pain presentation, and what's the impact. So, in the acute setting, we might be looking for inflammation or tissue trauma, but in some situations, there'll be a nerve injury or there's a degree of sensitization upregulation of the pain system.

And who is the person is, who is the occurring to? So, what's their education status. We know that's an influencing factor in transition from acute to chronic pain. But also the experience and the psychological neurological response to acute tissue trauma depends, to some degree, on the person, including their genetics, their education status, their past history of pain.

And then psychological and physical sort of perspectives. If someone is highly anxious or has been traumatized as a child, they will have a higher pain experience and a higher pain response. Imagine a traumatized animal, get them from the RSPCA, they're hyper vigilant, they're hyper reactive, so when a new injury comes along, they have a higher pain experience so it's important to recognize that so that then becomes part of the assessment process.

What's the impact from a respiratory, cardiovascular perspective in the acute setting. But in chronic disease, it's about, have they lost their job? What's the social impact? What's their psychological impact of having chronic pain?

Then we like to know about the journey. What is the expected trajectory of someone's pain event? And the expected expectation is that people get better. And if they are getting better, then you can follow that path, but if they're not going as expected, we should be intervening and that might be with nerve drugs with earlier psychological intervention, or with a close supervision of their opioid prescribing. And that includes social response interactions. And some of this work comes in TAC WorkCover where people after trauma, their pain rates go down, and then after about 12 months, the rates of pain tend to go up and a different mechanism is coming into play here. Workcover, TAC claim, attribution and blame, injustice issues become really relevant, and the brain changes become more important at that phase. So, the actual tissue trauma and inflammation early is not the same cause of contributing to pain late, after say a work cover injury.

And then how do we manage it? We really should be managing it from a social, psychobiological perspective. And patient education is the key, not just patient but then also flowing on to other health care practitioners and their family, and potentially also the legal system. From there, we think about what's the principles behind the drugs. Opioids are really there for nociceptive pain, but because they fail over time, you need to have a nerve drug to go with it to stop the drug opioid failure. So, with an anti analgesic and I'll explain more shortly. Non-steroidals, biologicals and antioxidants are really there for where there's inflammation. We use regionals but also nerve drugs for where there's obvious sensitization or nerve injury. So, we're targeting the drug program to the presumed mechanisms of this person's pain. Non -pharmacological, physical rehabilitation, re-exposure, psychological assessment and management for those with high factors psychological aspects to their presentation or their trajectory. And then social. There may be someone who's being held back by lack of legal representation or waiting for settlement so we need to address that as part of their pain condition.

I'll move through this quickly but essentially, if we get a tissue injury here, we get three main centres or sections of the brain. We get a sensory component, we get a mood and motivational component, and we get an evaluation. So we sensory feel it, we have an emotion that goes with it and we have an understanding of what it means and how we should respond. And so the brain activity patterns can change within the same person over time, depending on the social context, and that's been shown in a lot of studies. And that's why it's a multi-dimensional experience and it's almost always unpleasant.

And that's why we've got this concept of three mechanisms, a third mechanism of nociception to tissue damage, neuropathic nerve damage and up regulation of the nervous system. So, this might mean that it's been up regulated because they were traumatized as a child, or there's been a long poorly controlled pain, and there's up regulation of the nervous system to explain their heightened pain experience. So, clinically, we see this as sensitivity to pinprick, sensitivity to ice or heat, and people can be varied based on their genetics or their pre-exposure, pre-injury condition, but then also after the event.

Once you've experienced pain, you should be activating brain mechanisms to inhibit it called descending inhibition. But there's some groups that have demonstrated that you can actually up regulate the pain. So, if you are experiencing putting your hand in a bucket of cold water, that will activate the pain system and activate descending inhibition. But if you say there's a bottle of Moet in the bottom there versus a crocodile, you'll have a different level of descending inhibition. You want the Moet but you don't want the crocodile.  So, you can change it within the context. In addition, it can be changed by psychological features and there's a lot of experiments showing catastrophizing, which is one of the biggest predictors of someone recovering from acute pain, and that this can increase or decrease your brain response to pain. So, in general, those that are catastrophizing will have high anxiety levels, don't modulate their pain very well and they can up regulate quicker. So, we try to consider a person's nociceptor spectrum prior to an operation, but also just in their post-operative period and leading into chronic pain as to how that's influencing their experience. So, there's a biological basis for the psychological features of someone with pain.

And this is also seen in risk factor analyses. So, looking at social aspects that affect the trajectory but are associated with higher rates of chronic pain. And things like catastrophizing which has a genetic component, but adverse childhood experiences, parental style appears to change your risk of having chronic pain is twice as common than a control group if you've got abnormal parental bonding styles and behaviour.

Compensation and solicitation. So, workers' comp TAC but  anywhere between two, and some studies are up to five times the rate of chronic pain, if it's an injury where it was a work cover. You know, your boss pushed you down the stairs versus you fell down the stairs at home. Different outcomes based on the meaning of the event. And that leads into the perceived injustice which is a real interesting issue that's coming through here and making a big play on people twelve months to three years after injury.

Opioids also have an influence on the pain system, and so people who are exposed to an opioid can become sensitive to pain, and we will refer to this as opioid-induced hyperalgesia. It is a dose related phenomena so the high doses of opioids sensitises your pain system over a period of time. In addition, you lose your ability to suppress pain so you're opioid tolerant. So, this is really the two basic reasons why someone with a pain condition responds to opioids, responds to opioids not as effective, I need a higher dose doctor. I get a higher dose. So, that's good, that's good, that's good, I need a higher dose doctor. And so, you get dose escalation and they still have pain. And I think this is one of the driving features of why chronic opioids and chronic pain don't work particularly well.

I'll come back to that. Interesting. I'll leave this but essentially, people who meditate or have strong mindfulness components to their life have less pain unpleasantness and they have a different brain activation. So, if you've got a Buddhist coming for surgery, I say I don't need to give you much opioid because they can down regulate, and they've learned to down regulate and interestingly, their sensory experience goes up. They can feel that but it doesn't bother them. And that's because they've trained their brain to that point and it's one of the basis for why mindfulness is becoming very popular as a pain treatment because it's changing the brain and activating brain descending inhibition structures to a greater extent than placebo and in a different mechanism to placebo.

I'm going to move past this but that's something that is an interesting concept, so that for someone with acute pain who's in this trajectory period, we're now thinking, what are your risk factors? And what are your protective factors? And we want to treat your risk factors and boost your protective factors. So, education, social support, active coping, acceptance, higher self-efficacy, internal locus of control, lots of education, positivity can help people recover descending inhibition, promotes recovery from injury. But if you're highly distressed, you've been traumatized previously, you've just had more trauma, you've got fear avoidance, you're catastrophizing, it's an external locus of control, you've got someone else to blame for this, that's all negative, and that will up regulate your pain experience. And they're associated with poor outcomes and poor transition into chronic pain.

I'll move through this. There's a lot of data now about overdoing tests and particularly SCT and MRIs of the spine. We now do a lot more of these things called bone scan SPECT views looking for actual activation. So then this comes on to what are the other options there to treat chronic pain? If you don't want to use an opioid or if you want to limit your opioids.

Interventions. There's a huge industry now out there based around influencing that nociceptive pain physiology with needles, steroids, platelet-rich plasma, ablation of the nerves. Interestingly, vertebroplasty is about to come back into vogue as well. There was a number of studies of the negative, there's just been a recent acute study positive. So, they're starting to think, okay we should be putting cement into people with osteo product spine fractures. So there are a range of interventional approaches. The basic evidence base for them is not strong; it's probably weaker than opioids but it's an option.

What is strong is coming down the straight is explaining pain, and this comes out of Lorimer Moseley and in David Butler. Strong evidence base now that if you give the knowledge base to the patient, they will understand the neurophysiology. They can reinterpret it and they can re-evaluate the threat value of their sensation and their experience. That will help them transition into a recovery phase, so this is really a basis for a lot of the subsequent allied health based programs. It is actually a neuro physiological strategy that's aiming to improve the brain response so that you get less up regulation and greater down regulation of the pain experience.

And this is how we try to do it. We might start with someone with back pain. They come in, say I've got my scan here, I've got shocking discs, it's all somatic, it's all structural, and we have to transition their thinking from being one of a structural issue to one of a neurophysiological issue. And so, yes, we might talk about bone structures but it leads to this is the electrical pathway. You're getting pain and you're responding and you're up regulating. You're causing ongoing response. This is all influenced by your sleep, it's rolling into one, you're now distressed and disabled. We need to wind that back. So, patient education becomes really important.

Opioids, I'm going to run through, but essentially, less effective in chronic pain. In those that are prospective studies, we talk about a third do well, a third get side-effects and can't tolerate it, and a third don't get enough benefit. And the pain reduction is 30% versus in acute pain, it's 70%. If you ever see patients on high dose opioids, you need to be considering why, and there's some strong studies out of America showing association with anxiety states, psychological distress, PTSD, really strong affiliation between PTSD and pain, and that probably combined neuronal networks, and that they're using their opioid to suppress their trauma. And so, if you've got psychological distress and anxiety, your opioid dosing is double and sometimes triple what other patients would have in the same cohort.

There's substance use disorder or undiagnosed or previous substance use disorder, and then potentially cancer and palliative treatment. So, I'll comment on this and this is really from a science perspective. There is some support in the literature for opioids for chronic pain, non-cancer pain. So, there are some prospective studies. The problems are, we don't have a lot of long studies, we don't have studies on high doses. There is no difference with abuse deterrent formulations sort of coming into play now on this sort of meta-analysis. This has been reported in the lay press but it hasn't been through a peer-reviewed journal as yet, and it's saying a larger group of people put on opioids to 12 months, no difference for those non-opioid treatment. But it did go down. No difference with the pain interference, maybe they actually have a better pain response with those with non-opioid. I have not seen this published, it's just early days, but it's starting to get some press.

There's a whole range of opioids obviously and it's interesting to know that heroin goes to morphine as does codeine. So, there's three  delivery modules for morphine: codeine, heroin or morphine itself. It's just how quickly does it get into the brain, and what's the process to get it, and how much gets there? Fentanyl, Oxycodone now have abuse deterrent formulations. People say it's stronger than morphine but in actual fact when you put it into the brain, it's weaker. But it gets into the brain quicker and it's a bit more lipid-soluble, and it has the market share. 70% of the opioids on the market are Oxycodone. And so, we see people misusing Oxycodone. Is that due to the market share or is it due to Oxycodone? I don't think anyone quite knows.

To Pentadol, they tell us that it's less likely to be misused. I don't think we have enough experience yet and we definitely saw people with Tramadol misuse.

Buprenorphine. We've seen people with misuse of people morphine but it's come straight back into vogue from a pain point of view because of its safety profile and it has a built-in anti hyperalgesia effect, so you don't get that tolerance and dose escalation over time, and we've started to use it in acute pain intravenously, for people in moderate degree pain, giving them IV Buprenorphine and it would appear to be just as effective from a pain relief perspective, but safer from a respiratory perspective.

Matthew Fry's going to talk about that a bit more, I suspect. And so, I think this is definitely an option for treating the patient who are on high-dose codeine who are going to be brought to our attention that have been taking moderate dose opioid.

It is also safe in the older person and renal disease. I suspect it may contribute to falls, risks and cognitive dysfunction very early but there's compliance benefit.

We've talked already about the issues of codeine and this was the NNT issues that Malcolm Dobbin highlighted. There's one comment that hasn't come up and that is that codeine has a real propensity to activate the glial cells in the brain, and appears to be really sensitive in causing the hyperalgesia. And there's some studies in acute surgical episodes where people on low-dose codeine double the requirement for opioids post-surgery. And you think, well that doesn't make sense because they're on such a small dose. Why are they needing so much extra? Whereas people come in on morphine or other opioids and we tend to be able to match how much they're on and they use that plus a bit more post-op. But codeine, it's double and sometimes triple, and we suspect it's through activation of neuro inflammatory systems.

So, scientists will say, the codeine drug, not the morphine is an issue of about toxicity and brain toxicity addiction risks. I'm not sure if you're going to comment on it but the Victorian group who are going on to opioids have made a comment the other day that it's highly addictive. And I took I took umbrage at that. I think there is an addiction risk with opioids, and that is with all opioids. And for heroin, it may be 20%; Matthew what do you think? 20% maybe. So, if you go out there and shoot up heroin, you've probably got a one in five chance of developing a heroin habit. But for pharmaceutical opioids, it's probably in the order of three to four to five percent if you've got a few risk factors. But if you actually got no risk factors, the risk of addiction is low. And in these studies for acute pain, no history of abuse estimated …you're looking at about 0.5%, one in 200 chance, if you've got acute pain. But if you've got risk factors of genetics, alcohol abuse, psychiatric history abuse, history of past addiction, you're getting up to five to ten percent risk factor. You're not at the 20% risk of heroine with prescription medications. I think that's very important, so it's not everyone on them is going to get addicted. And that means that people who are taking codeine, they're not all addicted. They may be dependent but they may not be addicted.

This is the faculty pain medicine app. This is what we do. We treat with nerve drugs. Clonidine we use a lot because it counteracts some of the opioid tolerance and helps with dose reduction. It treats it as an anti-anxiety agent. And very strong about engaging psychological management. That's the app. The app has some total opiate calculator; it's really useful, and within it is the guideline pain management, 2015.

These are the other drugs I'll move through. Possibly we under use this which is Lignocaine patch. It's not on PBS but very helpful for shingles pain, it will reduce your opioid exposure. It's on the veterans PBS list but not the non-veterans group.

Allied health. So, in addition to that education, we're really arguing about trying to work around these unhelpful cognitions and behaviors. Work out whether they're ready to change their thinking for chronic pain and optimize their physical psychosocial function. And there's quite a lot of evidence base now for different allied health based coordinated pain programs in improving outcomes, both functional and reduce pain, and that there's all these acronyms for techniques. So, CBT, flexibility mindfulness. To me it's all about understanding their pain experience and then working them out of that position.

And this is based on New South Wales data. Electronic persistent pain outcome measures. If you see someone who's highly distressed, has high catastrophizing, they're going to need more work. And they're going to need a hundred hours, but if some one's not so disabled, not so distressed but they're still on an opioid and they've got good education, good prognostic factors, they may only need two to eight hours or a medium of twenty hours to get them toned up, to get them thinking right and they show progress. So, we should be targeting programs which are either individual low, medium, or high intensity based on their questionnaire studies.

It's combining and there's some benefit of having a group, having a physio and motor planning, plus psychological support, plus getting the family on board to stop the reinforcement, because you need three or four different angles to treat patients once they've become highly disabled.

There's a whole range of websites. This is the Better Health channel. This is the New South Wales one, and there's now internet-based pain programs, and there's two, both out of New South Wales. One is at Macquarie Uni and one is at St. Vincent's. And you can do a lot of these allied health based programs online. And this is really where rural medicine is going to go ahead if they can ever get the NBN going.

Chronic Pain Australia and APMA are the two big consumer groups. There's some help lines, there's some take stories, quite helpful, can reinforce it a bit but for a lot of people who are highly distressed, they need to know that there's other people there.

And from a GP pharmacy perspective, the faculty pain medicine have done a whole heap of work on modules, and found  better pain management. There's 12 modules on a whole heap of different things. An interactive, really strong from an education point of view. They're covered for CPT in most of the colleges, and they cover pretty well all these areas.

Pain Australia is mentioned, has a fact sheet on codeine, and a whole lot of fact sheets for both patients and clinicians.

These are the state resources and then there's pain clinics. So, when we talk about waiting in pain, everyone says, a lot of country GPs say, what's that point so I don't even refer them. But the studies we've done so far and there's an update to this project is that you're looking around three or four months for most services. Problem is if it's really chronic and being bumped, but if you triage it appropriately, if you say I'm distressed or do a telephone call, you can often implement changes before they get access to the pain clinic.

And that would be our promotion, that's the themes we're saying both to federal government and also state government. We need linkages between pain services and rural community health centres because we're going to be very reliant on the community care for that large volume of patients and the highly distressed disabled group get funnelled up into tertiary level care.

Now, I just want to finish with two minutes, one minute on the Victorian Government initiative, and I'm also on the advisory group or the external advisory committee for this. And essentially, they've just signed a contract with the provider, and they're going to go separately to the Tasmanian program, and the one that has previously been supported at federal level where there will be a database, and there'll be three access points to this database.

The first access point will be the GPs logging in to check. The second access point will be the pharmacist dispensing, and they will be saying I'm dispensing and it's now going into the system. And then the third will be the DHS will have access to that information, and they will collate information. So, then the patient comes back, the GP looks in and says, I can see you've had the script here, here and here. And then the pharmacy can say, oh I have a script here, here and here. Just like the road rules, you don't have to follow them so you can still dispense. You can still prescribe, but eventually there'll be someone doing a random breath test or something like that, or there'll be someone identified in this. And so, over time, we think this will be changed behaviour.

So, we improve the clinical care model that, I'm prescribing an opioid. Why am I prescribing it? Do you have pain? What's the benefit of the opioid? What's the functional benefit of it and reinforce it so it will lead to improved practice.

All Schedule 8 drugs, which will include and eventually will include codeine, as S4.

So, the combined drugs, codeine S4, all benzos, Zolpidem. Zopiclone and Quetiapine will be monitored with this system. You're looking at mid 2018. Not Tramadol at this point. They have done an extensive literature review looking at safety, and we used to say, what about Pregabilan and Gabapentin? There wasn't much in the literature on safety. Yes, there's misuse, and there's pockets of misuse, particularly in the prison sector, but but there's not a safety issue, whereas there is safety issues with Quetiapine and Zolpidem.

So, that's my comment and I will be talking later about rural settings. I think we're going to change and do Matthew's actually next if that's alright. So, I'd be happy to take any questions.

Any questions on this? Yes, one up the back there.

[Inaudible] Is that something you're suggesting patients do or GPs?

I think GPs do and I think pharmacists can work with their local prescriber to say, I've got a problem here. I need to communicate well with the prescriber, and if this person is misusing, I need support. We've got a hotline for drug and alcohol, we don't have one for pain, and I'm advocating that at a state level and potentially at a federal level that we get some funding to link in these services with the catchments that they provide.

Yeah. I don't know what the chances are. Well I don't know what it's getting to at this point, but I think if this if these changes come in and flush out this major problem, then they will respond to that. And that's the idea of the monitoring system thety are going to be sitting there, monitoring what's going on and going here we go, we've got a problem in this area. We're going to go out and do some education. We're going to strengthen our service delivery model in this area. They're going to strengthen to some degree drug and alcohol pathways, not quite so much pain, but eventually I think they will do pain.

Well I think they should be able to. They've all got nurses, they all respond, they respond to acute issues. You've just got to be a strong advocate for your patient and I think you can do it. The other thing is, we respond to emergency departments, so if you if you're getting nowhere, you send them into an emergency department. Say this person's on the wait list to see the pain clinic, I'm having trouble controlling their opiates.

Any other comments?

[Question is inaudible]

They will respond, so they will respond if there's an issue. They're going to add extra drugs to this as they come on board, but at this point in time, they've done an extensive literature review, and I'm happy to show you that document, and I can pull out the bit on Tramadol. In addition, Tramadol is going down in market share and ? is going up.

It's weak. It's really a week opiod.


Good. Actually, I'll be back for the rural bit. One more.

[Inaudible question]

Potentially, we have links with our pre-admission clinic. Most of the services will keep them on methadone or they'll split their dosing or drop their dosing a little bit to allow them to have opioid in theatre and then reduce it back down to their methadone. For some people, if they've been stable on a certain dose, they'll end up coming out on a slightly higher dose with the view to come back down again. It's all case-by-case. But you'll see you'll see much more ? use. Gabapentin, Clonidine, non-steroidals to treat someone who's already on methadone.

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