…but I thought a new knee would fix my pain!

Working in an orthopaedic surgery department is quite enlightening. Along with discussions about ceramic vs metal implants and cartilage regeneration (I work with a team of researchers looking at how to create replacement cartilage), the topic of what counts as a surgical success in knee surgery also comes up from time to time. Knee joint replacement isn’t as successful as hip joint replacement for a number of reasons including the complex nature of the joint, the way the joint capsule is disrupted during surgery, and the knee can apparently feel quite different from the original knee.

What this means is there can be quite a mismatch of expectations for people who believe very strongly that there should be no pain and they should have a completely normal knee joint after surgery. In fact, in the NZ National Joint Registry, the main reason recorded for knee joint revision is pain.

Naturally, the problem of pain after surgery is something surgeons and researchers are also interested in. Many studies have shown psychological factors such as catastrophising (thinking the worst) and low mood are associated with poorer outcomes (Riddle, Wade. Jiranek, & Kong, 2010; Roth, Tripp, Harrison, Sullivan & Carson, 2007; Shelby, Somers, Keefe, Pells, Dixon & Blumenthal, 2008).  The outcomes looked at so far include length of stay in hospital at the time of surgery, analgesia use during surgery, increased disability after surgery and revision rates.

Now, one solution to this problem could be simply not performing joint replacement surgery in people who are depressed and tend to think the worst. The problem is that two of the strongest predictors for looking for treatment are – you guessed it: low mood and catastrophising (and disability). Another solution is to provide intervention after surgery to target the people who tend to become fearful – perhaps an enhanced level of physiotherapy for this group, while the less vulnerable may even require less. Some studies have also looked at giving better education about what the surgery entails and the expected outcomes, and doing this before the person undergoes surgery, while another study has looked at providing a pain coping skills training course prior to surgery (Riddle, Wade, Jiranek & Kong, 2011). The outcomes from this last approach were promising, although it was a very small sample size, and the follow-up was for only two months.

There are a number of problems with implementing any of these approaches in clinical practice, at least in the system I’m most familiar with (NZ):

1. Many orthopaedic surgeons still discount the importance of psychological factors, and consider the information they provide completely adequate for presurgical preparation
2. It’s difficult to give someone different or special treatment based on psychological factors within a usual clinical setting without also inadvertently giving people a label that may change how they are responded to
3. Any additional intervention will have an up-front cost (not good for cost accountants!)
4. These treatments need specially trained clinicians who understand the measures being used, the rationale for treatment, and the type of treatment needed – and because these are psychological factors and surgery is conducted in a “physical” hospital, this is unfamiliar territory for many
5. Patients may not be very comfortable with a treatment that focuses on thoughts, emotions and pain

It seems to me, and from the results from a recent study looking at analgesic use after surgery, that an argument simply based on the cost of failing to go ahead with effective management of psychosocial factors would make sense. Here’s the detail:

Fuzier, Serres, Bourrel, Palmaro, Montastruc and Lapeyre-Mestre (2014) conducted a large study of patients in the Midi-Pyrenees region of France. They examined the medical records of all 1939 patients who had knee arthroplasty, and compared the drug use (what was dispensed) at four times – 12 months before surgery, 2 months before surgery, and 10 months before and after the knee surgery.  What they found was an increase in analgesic, antineuropathic and opioid drug use in the 12 months after surgery. The actual percentage of patients requiring more medication is astonishing: 47% of people needed more analgesia, 8.6% needed more antineuropathic medications, and 5.6% needed more opioids. That’s a whole lot of drugs!

These researchers also analysed a number of other variables associated with the medication changes, and made some more understandable findings:

• people having total knee replacement surgery were at a greater risk of using more medication than those having unicompartmental surgery (half a joint)
• people with high levels of preoperative pain along with “psychiatric vulnerability” were at greater risk of having increased neuropathic medications prescribed
• but older people were less likely to be prescribed additional medications

Unfortunately, this study didn’t identify the particular “psychiatric vulnerabilities” of the patients who participated – from the paper it looks like data was extracted from clinical records, so psychiatric disorders such as depression, anxiety and so on are the likely culprits. We don’t therefore know whether catastrophising contributed to the medication use – but given the results from at least 20 studies I have in my database, I think it’s probably likely.

Medications are not cheap. While they’re quick to prescribe, dispense and take, they cost not only in fiscal terms (which is a serious consideration, nevertheless), but also in side effects – and more importantly, in loss of personal locus of control. What I mean by this is that these are people who haven’t been given the opportunity to develop pain self management skills. They will continue to catastrophise, and perhaps even more so after surgery because their fears have been confirmed. Maybe it’s cheaper and more humane to bite the bullet and begin giving people appropriate psychosocial treatment before, during and after surgery.

Fuzier, R., Serres, I., Bourrel, R., Palmaro, A., Montastruc, J., & Lapeyre-Mestre, M. (2014). Analgesic drug consumption increases after knee arthroplasty: A pharmacoepidemiological study investigating postoperative pain PAIN®, 155 (7), 1339-1345 DOI: 10.1016/j.pain.2014.04.010

Riddle, D. L., Keefe, F. J., Nay, W. T., McKee, D., Attarian, D. E., & Jensen, M. P. (2011). Pain coping skills training for patients with elevated pain catastrophizing who are scheduled for knee arthroplasty: a quasi-experimental study. Archives of Physical Medicine & Rehabilitation, 92(6), 859-865.

Riddle, D. L., Wade, J. B., Jiranek, W. A., & Kong, X. (2010). Preoperative pain catastrophizing predicts pain outcome after knee arthroplasty. Clinical Orthopaedics & Related Research, 468(3), 798-806.

Roth, M. L., Tripp, D. A., Harrison, M. H., Sullivan, M., & Carson, P. (2007). Demographic and psychosocial predictors of acute perioperative pain for total knee arthroplasty. Pain Research & Management, 12(3), 185-194.

Shelby, Rebecca A., Somers, Tamara J., Keefe, Francis J., Pells, Jennifer J., Dixon, Kim E., & Blumenthal, James A. (2008). Domain specific self-efficacy mediates the impact of pain catastrophizing on pain and disability in overweight and obese osteoarthritis patients. Journal of Pain, 9(10), 912-919.

Pain and rheumatology: an overview of the problem

One of the most common reasons to visit a doctor is musculoskeletal pain. And one of the first symptoms of a rheumatological disorder is pain – so it’s great to find this succinct overview of pain in rheumatological disorders. I think one of the saddest findings I’ve read recently (I blogged about it a while ago) is that people who see a rheumatologist may have their disease process managed – but their pain problem may remain untouched. There is a misconception that pain is simply ‘a response to inflammation’ or ‘joint derangement’ – but it’s never really that simple!

This paper by Montecucco, Cavagna, & Caporali identifies five groups of pain disorder in rhematological diseases: acute pain, like gout, related to local tissue damage with nociceptive activation; chronic pain, which may be triggered by tissue damage or disease, but is often perpetuated by other factors such as central nervous system involvement – the three remaining groups of pain disorder are all subsumed under this chronic pain heading; inflammatory pain, such as rheumatoid and some osteoarthritis, involves increases in pain especially over night, with reduction after activity, and often with morning stiffness; mechanical pain, which is often a feature of osteoarthritis where the joint mechanics are altered – this pain is often worse during the day and relieved somewhat with rest, and although there may be some stiffness in the morning it usually lasts about 10 minutes or so; and the final type of pain is neuropathic pain, not often thought to be a feature of rheumatological problems, but involves disease or trauma to the somatosensory system – it could be peripheral, or it could be in the CNS and it may also be in response to heightened sensitisation secondary to the initial disease.

The authors briefly discuss fibromylagia – I posted about this recently also, discussing a paper that suggests perhaps FM doesn’t belong with rheumatologists at all, because it’s becoming apparent that it is a disorder of the central nervous system involved increased sensitivity to nociceptive input, probably associated with reduced functioning of the descending inhibitory pathways. Their suggestion is that it is ‘not clearly classifiable as inflammatory or mechanical’, but they’re not prepared to include it in the neuropathic group because the pain experience is slightly different.
Neuropathic pain is thought to be more commonly perceived as burning, tingling, hyperalgesia especially to hot or cold, and often involving allodynia.

The paper goes on to review the epidemiology of rheumatic pain. I don’t think there would be many who would argue that chronic pain associated with these problems is common and this paper indicates there is research to suggest it is an increasing burden even in developing countries such as Vietnam, Peru and China. Despite this increasing prevalence, the underlying disorders vary from country to country.

The burden of pain is also discussed – rheumatic diseases are probably the most prevalent cause of functional limitation that does not reduce life expectancy. While pain doesn’t kill, people live a long time with poor function, lowered quality of life, and use a wide range of support services including health care in this time.

I was struck by the estimates of the economic cost of pain in these disorders – 1 – 2.5% of GNP in USA, UK, France and Australia. OA is thought to cost the USA more than $60 billion per year.

The final quite brief section in this paper draws attention to the different ways in which people express their pain – I couldn’t agree more. Psychosocial factors are integral to the pain experience, so it makes sense to include psychosocial management along with disease management. Would that this happened where I work – sadly, though, the rheumatology clinics don’t routinely have pain management using any approach let alone a cognitive behavioural one! And this despite many studies showing the effectiveness multi and interdisciplinary pain management using a cognitive behavioural approach on the lives of people with these painful conditions.

This paper is a very brief summary of pain in rhematological disorders, but as an overview it does what it oughta. I like the many references, and they’re all quite recent, so if you’re wanting to get your head around pain in these problems, it is a worthwhile paper to get hold of.

Montecucco, C., Cavagna, L., & Caporali, R. (2009). Pain and rheumatology: An overview of the problem European Journal of Pain Supplements DOI: 10.1016/j.eujps.2009.07.006

‘Placebo’ response in osteoarthritis – what does it mean in practice?

One of the most maligned but to me most fascinating aspect of health care is the human response to placebo.

Placebo is an inert substance – or at least, a substance that is objectively without specific activity for the condition being treated. Dan Moerman has written about the so-called ‘placebo response’ and suggests that it should be called the ‘meaning response’ because humans attribute meaning to the interaction between a health care provider and a patient, and he argues that it is this meaning that influences the response in the patient. This definition is helpful for moving the source of ‘action’ in a placebo away from the inert substance and on to the interaction between the treatment provider and the person in whom the response occurs.

There are loads of reasons for researchers to be bothered by the meaning response – all of these randomised controlled trials in which one arm of the research uses placebo are confounded by the numbers of people who respond positively despite receiving the placebo dose (oh and yes, they can also respond negatively – the ‘nocebo’ effect that might include ‘side effects’ like nausea or headache). The gold standard in research is to compare the results of giving nothing with the results from giving an active ‘something’ – so to have the ‘nothing’ produce an effect is pretty awkward.

This paper by Doherty and Dieppe reviews the evidence for placebo response in randomised controlled trials in treatments for osteoarthritis. The authors specifically looked for trials with no treatment control groups, and to identify possible determinants of the size of any such effects. They reviewed 198 trials that met the inclusion criteria – 16,364 patients who had received placebo and 1,167 patients who had received active treatments of many types including pharmacological, nonpharmacological and invasive treatments.

The good news? Well, receiving placebo had a positive response for pain reduction (effect size of 0.51 (95%CI 0.46 to 0.55). Oh darn, that wasn’t what was being tested? If the patients received nothing (ie the research didn’t include a placebo group, but instead had a non-treatment comparison group), the effect size was almost zero (ES 0.03, 95% CI -0.13 to 0.18). So giving nothing at all meant nothing changed. The effect size was even higher in head-to-head comparisons between placebo and no treatment (ES 0.77, 95% CI 0.65 to 0.89). So giving something that doesn’t have an active ingredient works better than giving nothing at all. Curious.

The authors go on to identify significant independent effects for the outcome of pain relief – these include that the higher the treatment effect size, the higher the placebo effect; the higher the pain was initially, the greater the effect size in the placebo group; the larger the study, the higher the placebo effect; and finally, how the treatment was delivered made a difference as well – repeated needling had the highest placebo effect.

The scary thing for me is knowing that there is a systematic bias, demonstrated by a skewed distribution of the effect size, suggesting that ‘trials with smaller placebo effects are more likely to be published, perhaps because it is easeir to demonstrate the superiority of a treatment when this occurs’. But this effect size is influenced by the size of the study – so be aware!

Back to what this means in practice. We need to review what may be going on when a person receives a placebo (and, for that matter, an active treatment). There is a good deal of research on the factors that are known to influence the ‘meaning response’ in people. Dan Moerman’s book ‘Meaning, Medicine and the ‘Placebo Effect’ reads well, and describes some of the known factors – such as mode of delivery (injections are more likely to produce a greater effect than a pill); colour of pill (pink pills are responded to as stimulating, while blue pills are responded to as sedating); number of pills (more pills = greater effect); and the bits I’m most interested in, response expectancy, conditioning and the relationship between the person and the treatment provider.

Response expectancy is the expectation a person holds about what the treatment will do. Being told what a treatment is meant to achieve influences outcome – so we know that if we infuse our instructions about going for a walk with the idea that not only does it help with mobility and fitness, but it makes you feel good – then participants are more likely to report feeling good after a walk than those who didn’t get that instruction. Simply knowing that a treatment is being given has an effect – whether that treatment is placebo or not.

In conditioning, the response is associated with an aspect of the treatment – for example, in this paper, the authors describe people being given a green liquid to drink along with an immunosuppressant. After four doses given this way over a week, the participants were then given four doses of a placebo and the green liquid over a week – and lo and behold, the same immunosuppression response occurred.

Where the treatment occurs is also highly significant. Pleasant surroundings seems to improve recovery, a quiet tranquil setting aids relaxation, a messy office does not inspire confidence (hence I don’t see people in my office!).

And the final ingredient is the relationship between the person receiving the treatment and the person giving the treatment. From the words used, the attention given, the ‘therapeutic ritual’, even the amount of time spent with the person – these all influence the response in the patient.

What does it mean?

Doherty and Dieppe suggest that because placebo affects ‘the illness’ rather than ‘the disease’ (ie pain rather than x-rays), the value of it is primarily for patient symptoms and distress.  I’m not surprised – these are the targets of many interventions for painful conditions such as low back pain, headache and so on.  They, somewhat surprisingly, suggest that ‘we should be more aware of the power of the placebo response to relieve pain and suffering in people with OA, and that we should learn how to use it better’. My surprise is that it’s not the placebo that we want to use – after all, placebo is inert – it’s the meaning response we want to influence in patients, so they can maximise the positive benefits from the interactions they have with us as treatment providers.

The recommendations Doherty and Dieppe suggest don’t sound over the top – being calm, unhurried, focusing on the patient, having a comfortable environment, explaining what is going on in terms the patient understands – isn’t this basic human compassion? This is, as Doherty and Dieppe acknowledge, a treatment.  (Isn’t this so true of so-called complementary health consultations? Maybe that’s why they have such a profound effect on some people).   Perhaps if we valued time and caring (and made sure these were never compromised irrespective of the demands to ‘increase throughput’), our patients might benefit as much as we would?

Doherty, M., & Dieppe, P. (2009). The “placebo” response in osteoarthritis and its implications for clinical practice Osteoarthritis and Cartilage DOI: 10.1016/j.joca.2009.03.023