doi:10.1016/j.ijosm

International Journal of Osteopathic Medicine 8 (2005) 121e123

www.elsevier.com/locate/ijosm

Editorial

To what should we attribute the effects of OMT?

On the basis of a recent meta-analysis, Licciardoneet al.1 conclude that osteopathic manipulative treatment(OMT) reduces back pain to a greater extent than doesplacebo. The emphasis on demonstrating that a treat-ment is more effective than placebo is at the forefront ofevidence-based medicine. It is the ‘holy grail’ of studiesin chronic pain populations, yet is so very often elusive.While the pursuit of specific treatments for specificdiagnoses is vital in improving patient health outcomes,advances in the understanding of placebo responseswarrants a re-conceptualisation of how the placebophenomenon might relate to OMT.

Placebo responses, or non-specific responses as theyare also called, occur in people of different age, gender,race, personality and educational level. Placebo analge-sia is a term used to describe the phenomenon of painrelief following the application of non-specific or shamtreatments, when the patient believes that they havereceived an active or specific treatment. However,placebo responses are not limited to the modificationof pain. Other placebo responses include respiratorydepression,2 reduced heart rate and decreased b-adrenergic response,3 and increases in growth hormonesecretion.4

Even if a treatment is shown to be more effective thana placebo, it does not follow that the entire response canbe attributed to specific effects of the treatment. Ifa placebo was shown to reduce pain by 50%, and OMTwas shown to reduce pain by 60%, then the specificallyattributable effect of OMT is only 10%. However, towhat should we attribute the remaining 50% improve-ment in the OMT group? To attribute it to ‘placebo’,without further consideration of the mechanisms ofplacebo, is perhaps a little too superficial. While it is notusually considered ethical to offer a placebo in clinicalpractice, it is ethical to offer a treatment that might be5/6 placebo and 1/6 active treatment (using the abovehypothetical example). This distinction may be viewedas somewhat irrelevant, as irrespective of the mecha-nisms involved, the active treatment is either better thanplacebo, or it is not. However, the value in considering

.2005.09.002

which mechanisms might underlie the total treatmenteffect of OMT lies in the possibility of enhancing each ofthese mechanisms, and of the possibility of specificallyactivating these mechanisms. While it is encouraging tolearn that OMT produces pain relief in excess of placebotreatments, it would be useful to understand how OMTinteracts with non-specific placebo responses, andwhether there are specific placebogenic responses toOMT? It may be that OMT is a useful and specifictrigger of a non-specific mechanism of endogenousanalgesia. Alternatively, the non-specific placebo re-sponse may actually potentiate the action of OMT. Oneway to analyse this relationship experimentally would beto conduct a controlled trial of OMT for pain relief andrandomise patients to receive an injection of either salineor naloxone (an opioid antagonist). Naloxone has beenshown to block and reverse placebo mediated analgesia5

and would thus help to determine to what extent theeffects of OMT rely upon this mechanism.5

To further explore this issue, we can draw on somefascinating research. In 1995, Benedetti et al.6 demon-strated a remarkable aspect of the placebo response.Using what is referred to as an open-hidden design, theycompared intravenous injection of proglumide (acholecystokinin antagonist) with normal saline in thetreatment of post-operative pain. In the ‘open’ phase ofthe study, patients were randomised to receive aninjection of either proglumide or saline. In the ‘hidden’phase of the study, patients were randomised to receiveproglumide or saline via a computerised pump, and werenot aware that they were receiving an injection.

In the open phase, saline produced significant painrelief; however, proglumide proved to be significantlybetter than saline. On the basis of this RCT it could beconcluded that proglumide was an effective analgesic.However, in the hidden phase, proglumide and salinewere equivalent and the both were ineffective at pro-viding pain relief. This is a fundamental point toconsider. When the patient didn’t know that they werereceiving an injection, the specific drug was no betterthan placebo, and neither provided any pain relief.

122 Editorial / International Journal of Osteopathic Medicine 8 (2005) 121e123

However, when the patient did know that they werereceiving an injection, the specific drug provided betterpain relief than placebo. The essential ingredient,therefore, was the patients’ knowledge of the injection.This is not to say that patient knowledge alone wassufficient, for if this was the case saline would haveproduced the same result as proglumide in the ‘open’phase. However, what can be concluded is that in orderfor proglumide to perform better than saline, it wasnecessary for the patient to be aware that they werereceiving it. So, rather than proglumide having its ownspecific effect on pain pathways, there was a physiolog-ical interaction between the biochemical events triggeredby placebo response and the pharmocodynamic effectsof proglumide. There are other examples of thisphenomenon in post-operative pain. In one study,a ‘hidden’ injection of 6e8 mg of morphine was nomore effective than an ‘open’ injection of saline.5 Usinga ‘hidden’ injection of morphine, 12 mg was necessary inorder to achieve an analgesic effect greater than an‘open’ injection of saline.7,8 Obviously, such researchdesigns are impossible to apply to OMT, but onewonders if the same type of interaction is occurring withOMT?

The best understood physiological mechanism ex-plaining placebo analgesia is that of the endogenousopioid system. The best understood psychologicalmechanisms for placebo analgesia are expectation andPavlovian conditioning, which are known to activateopioid mediated pathways.4 For example, if someonereceives OMT and their pain is relieved, they develop anexpectation of what will happen the next time theyreceive OMT e and further they have become positivelyconditioned to respond to OMT. We can thereforeconsider the likelihood that the effectiveness of a treat-ment is a combination of both specific and non-specificmechanisms; and rather than trying to enhance only thespecific mechanisms, we should also consider how wemight purposely enhance the non-specific mechanisms.

The following conceptual equation demonstrates thateffectiveness is the result of the specific (S ) effects ofa treatment in addition to the non-specific (NS) effectsof the treatment.

EffectivenesszSCNS ð1Þ

The effectiveness of a treatment is expected toincrease if the specific effects or non-specific effects ofthe treatment are increased. It also follows that if thespecific and/or non-specific effects of a treatment arereduced, then the effectiveness of the treatment will bereduced.

Based on an understanding of the major psycholog-ical mechanisms of placebo analgesia,4 another simplis-tic conceptual equation can be constructed to describethe relationship between expectation (E ) and conditioning

(C ) in determining the ‘magnitude’ of the non-specific(NS) effect, or placebo response.

NSzðpE� nEÞCðpC� nCÞCx ð2Þ

where pE is positive expectation; nE is negativeexpectation; pC is positive conditioning; nC is negativeconditioning; and x is a factor that is representative ofother important variables that affect the placebo re-sponse (e.g. belief, motivation).

In Eq. (2), the greater the value of positiveexpectation (pE) and positive conditioning (pC), thegreater will be the value of NS. Any amount of negativeexpectation (nE) or negative conditioning (nC) willobviously diminish the value of NS.

It is interesting to consider how the specific effects ofa treatment might interact with the non-specific effectsof that treatment. For instance, since Licciardone et al.1

report OMT to be more effective than placebo in thetreatment of low back pain, this knowledge will increasethe positive expectation of osteopaths, which may inturn increase the positive expectation of the patient. Anincrease in positive expectation will increase the non-specific effects, which in turn will increase the overalleffectiveness of OMT. The irony is this: the more specifica treatment becomes, the more practitioners are likely toenhance, via positive expectation, the non-specificelements of that treatment. This phenomenon mayexplain why patients, who have received OMT in thepast, may have a greater response to OMT than thosewho have had no prior experience with OMT, as wasdemonstrated in a recent study.9

Of course, these simplistic conceptual equations arenot literal, and are likely to be false analogies. Forexample, there may be a ceiling effect on non-specificresponses, meaning that once a certain value of NS isachieved, no further increases in expectation or condi-tioning will result in higher values of NS. Also,expectation and conditioning have more than a simplelinear and additive relationship.

Whether OMT is shown to produce similar or greatereffects than that of placebo treatments, the fact remainsthat these non-specific responses are an importantfeature of the self-regulatory mechanisms of humanpsychophysiology. Rather than viewing OMT as some-thing that should be separate and distinct from non-specific placebo effects, perhaps the effectiveness ofOMT depends to some extent upon an interactionbetween OMT and placebo responses?

References

1. Licciardone JC, Brimhall AK, King LN. Osteopathic manipulative

treatment for low back pain: a systematic review and meta-analysis

of randomised controlled trials. BMC Musculoskel Dis 2005;6.

doi:10.1186/1471-2474-6-43.

123Editorial / International Journal of Osteopathic Medicine 8 (2005) 121e123

2. Benedetti F, Amanzio M, Baldi S, Casadio C, Maggi G. Inducing

placebo respiratory depressant responses in humans via opioid

receptors. Eur J Neurosci 1999;11:625–31.

3. Pollo A, Rainero I, Vighetti S, Benedetti F. Placebo analgesia and

the heart. Pain 2003;102:125–33.

4. Benedetti F. Conscious expectation and unconscious conditioning

in analgesic, motor, and hormonal placebo/nocebo responses.

J Neurosci 2003;23:4315–23.

5. Finniss DG, Benedetti F. Mechanisms of the placebo response and

their impact on clinical trials and clinical practice. Pain 2005;114:

3–6.

6. Benedetti F, Amanzio M, Maggi G. Potentiation of placebo

analgesia by proglumide. Lancet 1995;346:1231.

7. Levine J, Gordon N. Influence of the method of drug administra-

tion on analgesic response. Nature 1984;312:755–6.

8. Levine JD, Gordon NC, Smith R, Fields HL. Analgesic responses

to morphine and placebo in individuals with postoperative pain.

Pain 1981;10:379–89.

9. McReynolds TM, Sheridan BJ. Intramuscular ketorolac versus

osteopathic manipulative treatment in the management of acute

neck pain in the emergency department: a randomized clinical trial.

J Am Osteopath Assoc 2005;105:57–68.

Nicholas LucasUniversity of Western Sydney,

School of Exercise and Health Sciences,Locked Bag 1797, Penrith South, DC NSW,

Sydney 1797, AustraliaE-mail address: n.p.lucas@uws.edu.au