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11 Articles in Volume 7, Issue #4
Cervical-Medullary Meningioma
CES in the Treatment of Depression
Deep Penetration Therapeutic Laser
Fibromyalgia Patient Insights
Invoking the Placebo Effect
Multidimensional Ultrasonography
Paradigm Shift in Cancer Pain Management
Prolotherapy for Low Back Pain
Sedation Levels for Intraspinal Injections
Self-Protection Against “Off-label” Lawsuits
Viewpoint: Methadone Successes and Cautions

Invoking the Placebo Effect

Meaning, Mechanisms, and Morality of the Placebo Effect in Pain Management

The modern physician has at his command powerful remedies… he cultivates nevertheless a… manner that contributes to his therapeutic effectiveness… a miraculous moment comes when the doctor becomes the treatment.” —René Dubos

In addressing the mechanisms by which spiritual experiences and spiritual practices affect pain, it becomes apparent that these events engage pathways that can both modulate pain and initiate a variety of physiological, and salutogenic processes.2 This supports the concept that particular external events—whether environmental, ritual, or interpersonal—engage one or more sensory systems, activate the peripheral and central nervous system, evoke cognitive substrates involved in different types of memory and emotion, and generate a change in the somatic state.3 This instigates both directed actions/behaviors and the phenomenon of the bodily response and external provocation, that are perceived as a ‘mind state.’ This is what Damasio has called the ‘feeling of what happens’ and is intrinsic to sentient experience.4

We possess a pain modulating system that is non-linear, adaptive, responsive to internal and external environments, and which can be environmentally and circumstantially conditioned.5 While such responses are common, if not universal (not only to humans, but perhaps many mammalian species), the extent to which these systems are responsive, and the fortitude and pattern of responses all appear to be individually variant. Individual responses are determined by genetic predisposition and epigenetic-phenotypic interactions with various environmental factors throughout one’s lifespan. Hence, we possess both the substrates for pain (as sensation, perception, and conscious event), as well as mechanisms by which pain (in all its dimensions) may be modulated or suppressed. The adaptability of these mechanisms allows not only reduction of pain, but also reduction of many of the correlated physiologic processes (e.g., inflammation, immunologic changes, etc.) that perpetuate potentially maladaptive cognitive responses and may impede repair and recovery.

Recent work by Wachholtz and Pargament has shown that spiritual experiences and practices increase pain tolerance, decrease anxiety, and reduce negative, cognitive and behavioral features associated with pain and distress.6 If we accept the philosopher Leon Kass’ definition of health as an integrated “wholeness,”7 then a role of spiritual experience and practices may be to facilitate salutogenic effects in the strictest sense: by preserving or enhancing the sense and, perhaps, the functional basis of “integration” that is “health,” and by decreasing the dis-integration incurred by pain—particularly chronic pain as illness.

Our growing recognition that such experiences and the effects they generate are relevant to the clinical encounter should not be wholly surprising, as the use of ritual to enhance susceptibility and promote readiness to healing experiences has been characteristic of shamanic practices throughout history.8 Creating a sense of expectation that a healing would occur thereby established the reciprocity of the encounter. In the Aesclepian tradition, it was believed that the attendance of the graces (notably Hygieia and Panacea) established and maintained the durable healing power of the Aesclepian ‘cure.’9 To be sure, the notion of a ritual evoked by the physician’s demeanor and actions was critical to Hippocratic medicine.10

The focus of the clinical encounter is the good of the patient, for it is the patient who seeks the physician’s professed skills to effect a healing. The satisfactory outcome of the clinical encounter may not entail cure, but must involve care. To paraphrase Hippocrates, the regard for the patient is the art, and such positive regard is therefore instrumental to the ends of medicine to render a right and good healing.11,12 Is it not rational to assume that the supposedly “mystical” nature of shamanic healing—when interpreted in light of our contemporary understanding of neural mechanisms of expectation and belief—may, in fact, still be an important element of the modern clinical encounter. Simply, if the patient seeks the physician with some expectation (i.e., “hope”) of healing that is based upon the physician’s profession (i.e., literal declaration of knowledge intent and skills), then it is clear that the moral obligation of the physician is to prudently act within reason to attempt to realize that which has been professed by maximizing the good for, and of, the patient.13 In this sense, the tenor of the clinical encounter should “please” the patient by meeting the expectation for a positive interaction with the physician and that, at very least, does not harm.

It is in this light that I offer a re-examination of the concept of placebo. Literally translated from the Latin, “placebo” means “I shall please.” Given the aforementioned premises of the clinical encounter, is that not essential to the act of medicine, at least in the context of care, hope and expectation arising from, and within, the physician-patient interaction? The notion of placebo as an ‘inert agent’—while relatively viable in the research literature to refer to a sham treatment—should be reconsidered, both in terms of the apparently non-specific effects that such ‘inert’ treatments produce, and the relevance of such ‘placebo effects’ to clinical practice. Taken in accordance with the literal definition of placebo ‘to please,’ it is important not to misregard placebo as a mere placation. This is etymologically incorrect, conceptually inaccurate, and ethically unacceptable. Rather, placebo effects are those processes—or events that engage resultant processes—that are facilitative to healing.13 In this way, placebo effects might be better considered as patient-specific biopsychosocial effects. Unfortunately, however, the ambiguous terms placebo and placebo effect—retaining a considerable burden of ‘folk’ meaning and reflecting a connotation of sham treatment—still persist. It is this folk interpretation that has led to definitional ambiguity and ethical consternation regarding the use of placebo effect in medical practice. Not unlike the notion of ‘spirituality’ (as confused with religion or religiosity), such definitional ambiguity can sustain both philosophical and pragmatic problems.14 Also, like spirituality, a mechanistic understanding may be critical to increasing the relevance and resonance of such processes to medicine.

Possible Mechanisms of Placebo Effect(s)

While there appear to be a number of mechanisms involved in placebo effects that may be differentially engaged by particular environmentally interactive cues, most appear to involve expectational and integrative cognitive networks that engage limbic, paralimbic, and midbrain/centrifugal neuraxes.15 Specifically, early phase placebo effects engage the frontal and prefrontal lobes—brain regions that contribute to network processing of expectation16—and decreased activity of the anterior insula, thalamus, and anterior cingulate gyrus—regions involved in both pain sensation and the perception of noxiousness.17 Hrobjartsson and Gotzsche suggest that the engagement of these mechanisms reveals a direct sensory, not just perceptual or judgemental modulation of pain.18 The engagement of the periaqueductual grey (PAG) and resultant centrifugal analgesia in placebo effect supports this contention.19 Additionally, late stage reduction of cingulate and amygdalar activity in placebo analgesia demonstrates that these mechanisms are progressive and relatively durable.20

Conversely, negative (i.e., nocebo) effects that activate nociceptive sensory and/or cognitive pathways and diminish endogenous pain modulation have been observed in response to negatively valent environmental interactions, including expectational failure.21 It may be that repeated clinical failure or expectational dissonance may incur nocebo effects that heighten the linearly-disruptive mechanisms of persistent pain, and further induce therapeutic refractoriness. It is obvious that an understanding of these mechanisms and their potential to affect patient responses and therapeutic outcomes is important, both to the general practice of pain management and to the pragmatic and ethical specifics of the clinical encounter itself.

Ethical Considerations

The fundamental ethical issue is how placebo effects might be elicited and engaged in the pain patient. While there is certainly ‘discretionary space’ that the physician must carefully establish to afford some latitude in how much information should be provided to a particular patient, outright deception is contrary to the veracity that establishes trust within the physician-patient relationship.22,23 The asymmetry of knowledge and power between physician and patient reinforces the fact that the physician, as steward of knowledge, must utilize both objective knowledge of fact, and subjective knowledge of the patient to best provide care that is right and good.24 Beneficent actions must be grounded by prudent selection and use of such knowledge. The moral obligation is to provide therapeutically competent care that focuses upon the patient’s best interest. Further, the therapeutic obligation must adhere to the moral ends of medicine as humanitarian practice. In this way, moral and therapeutic intentions and actions are reciprocal and somewhat inseparable.

Conclusions

Understanding that there are endogenous mechanisms that can facilitate pain modulation, healing responses, and enhance medical intervention(s) to improve therapeutic outcomes affords considerable insight into this potentially powerful clinical effect. But insight does not always give rise to good judgment. The power of any knowledge lies not in its potential, but in the prudent judgments and acts that allow its use as a tool that is both consistent with, and pursuant to, the morally sound ends of medicine. How then can, and should, placebo and placebo effects be utilized within pain management? Simply, I urge a re-focus not upon placebo as an inert agent that induces some positive effect(s), but upon the actions of the clinician as an agent to evoke placebo effects that are contributory to more positive clinical outcomes. Without doubt, there will be times when diagnosis and/or effective treatment remain enigmatic and elusive, and when the pain patient may frustrate the expert knowledge of the physician. That is the nature of pain medicine. No two pains are alike, for no two brains are alike, and this understanding is fundamental to the realities of practical pain care. The practice of pain management may be difficult and laden with compound responsibilities. But I have argued previously—and reiterate here—that while the choice to be a pain physician is discretionary, choosing to be a pain physician obligates acceptance of the facts of pain, the realities of the practice, and the moral responsibilities inherent to it. Pain, on the other hand, is not discretionary and the vulnerabilities and expectations it incurs are profound.25 It is in this context that Mark Boswell and I have described placebo as “… not a sham intervention… but as a consequence of the clinical encounter itself.”26

Understanding the patient is just as important as understanding the processes of pain, for such processes ultimately produce subjective effects within the lifeworld and objective body of the person in pain. Determining the right treatment often requires pairing objective knowledge (of pain mechanisms and differing therapeutics) to the subjective context of a particular patient.27 And while the right treatment may require trial and error within an empirical approach, it is often the “good” of the treatment—the communication of intention, non-abandonment, and hope—that sustains the trust necessary to meet the patient’s expectations within continued care. The placebo effect does not involve deceiving patients about inactive treatments. To the contrary, I argue that placebo effects can be gained by the physician’s actively affirming his/her role in upholding the patient’s hope: by both the use of the most modern skills, techniques and technologies, and by the preservation of the durable interpersonal dimensions of medicine as humanitarian art. n

Last updated on: February 28, 2011
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