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Diversity in Pharmacologic Treatment of Pain

An essay on the neuroscientific, ethical and policy issues surrounding pharmacologic pain care in light of certain controlled substances that, while efficacious in certain patients, may be problematic in practice.
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Pharmacologic Pain Care— From Epistemology to Ethics

Pharmacologic management of chronic pain remains problematic in that it often evokes questions and issues at the practical intersection of biomedical science, ethics and law. In the first domain, the recognition that chronic pain and its modulation are subserved by heterogeneous substrates and mechanisms that involve a variety of neurochemical systems is essential to any consideration of what agents would be viable to target one or more of the elements on the nociceptive neuraxis. This information enables a more thorough recognition of how certain neuroanatomic and neurochemical elements contribute to pain, and how they can be engaged to affect change(s) in nocicpetion and/or analgesia. This provides a basis for determining what agents in the contemporary pharmacopeia might be viable and valuable to produce desired levels of pain relief. In other words, such information affords insight to the first two critical questions, and discerning steps, of the clinical encounter, namely, the determination of what is wrong with a particular patient and what can be done to remedy their predicament. 1-3 Given the complexity of chronic pain, it is axiomatic that its pharmacologic management requires a diversity of agents —both to address individual differences inherent to the neurochemical profile of each patient’s pain and to engage pain- and treatment-related changes in an individual patients’ neurochemistry that occur over time. As I have often stated, our current knowledge of pain dictates against overly simplistic, “cookie cutter” orientations to practical pain management. 1,2,4 To be sure, this is becoming evermore relevant in light of calls for—and a trend towards—personalized medicine. Any realistic assumption of such a personalized approach to pain care would need to consider individual genotypic and phenotypic variations in nociceptive and anti-nociceptive systems at least as a starting point and/or basis for the development and implementation of appropriate pharmacotherapeutic regimens. 5

Personalized Pain Medicine

In many ways, a personalized pain medicine could be seen as most directly serving the primacy of each patient’s best interests in that it is grounded to the uniquity of the individual and thereby avoids “one size fits all” approaches to care. Certainly, knowledge of specific neurobiological bases of a given patient’s pain is critical but it is equally (if not in some cases more) important to consider and appreciate how psycho-social factors influence—and are affected by—the experience and expression of physiological variables. Simply put, humans are bio-psychosocial beings and pain is manifest in, and impacted by, each of these dimensions. This view is not esoteric. Rather, such an epistemological orientation to the person in pain and the effects of pain upon the lived body and life world of each person provides a foundation for the ethical responsibilities that arise from, and are entailed by, this position. 6,7 A more complete depiction of each patient’s bio-psychosocial individuality would:

  1. allow greater specificity in selecting what therapeutic interventions could be viable;
  2. facilitate resolution of equipoise in clinical decision-making, and thereby
  3. fortify prudential formulation of a care plan that is consistent with each patients’ (medical) needs, life values and goals, as well as the expert insights and therapeutic goals of the clinician. 8

This illustrates the relation of knowledge to ethically sound clinical practice—at least in principle. But, to quote an old adage: There is much to divert the egg between the chicken and the pan…

The Medical and Socio-Legal Realities of Pharmacologic Pain Care

Neuroscientific data that identifies that—and how—opioid, glutaminergic, GABA-ergic and monoaminergic systems are involved to varying degrees in the modulation of certain types of pain is undeniably critical to devising a pharmacotherapeutic regimen. Still, such data can be seen as “theoretical” or “conceptual,” and determination of the actual extent that these systems are engaged remains inferential for various reasons:

  1. measurements of central neurochemistry are impractical and/or overly invasive (i.e., requiring assessment of cerebrospinal fluid via lumbar puncture);
  2. are expensive and thus are characteristically used only in the research setting (e.g., use of radiolabeled ligands to determine differential activity/sensitivity of various CNS substrates); and/or
  3. not yet available at the level of accuracy or reliability necessary for broad clinical use. 9-11

In light of this, the use of any pharmacololgic agent is based upon empirical outcomes and existing levels of evidence gained in clinical trials and practice. In this latter regard, professional guidelines are formulated that suggest particular utility and parameters (e.g., dose, schedule, contraindications, etc.). Ultimately, however, policies and laws afford the most over-arching regulation to dictate and/or direct clinical provision and use of pharmacotherapeutics. However, a somewhat less overt level of control is effected through indirect regulation imposed by economic and market forces such as the availability of insurance, insurance-coverage dictates of the types and extant of use of particular agents and the portfolio of various hospitals’ pharmacopeia. 12 These elements are frequently non-aligned and, in many cases, may actually be dissonant and create situations in which the provision of necessary care cannot be achieved because of economics, policy, and/or law. To reiterate, chronic pain is frequently a complex entity that involves multiple anatomic and neurochemical mechanisms. But, such complexity does not refute the benefit of parsimony when executing clinical therapeutics. The right use of limited, but potent, pharmacotherapeutics will often provide the simplest means to achieve the best results in alleviating pain and restoring function. But here we may encounter an antinomy. What if the simplest solution fosters further complications? In other words, what if the right treatment—that also affords the most potential good—also incurs considerable difficulty, burden, and perhaps harm? For example, the prima facie use of opioid analgesics can be considered to provide meaningful benefit to patients with particular types of pain. Yet, even under ideal circumstances, we cannot deny the potential medical, ethical, economic, and legal issues that may arise in and from the use of such agents. Moreover, prima facie considerations very often pale in the glare of the multi-dimensional factors that constitute the realities of pain, pain patients, and their existential circumstances. Often, these are influenced by dispositions within the medical and socio-legal milieu that are based, at least in part, upon the ways that pain and its manifestations are defined and characterized. Despite an underlying incentive for overarching moral regard, such dispositions commonly affect public, medical and legal attitudes as well as conduct toward pain and the pain patient. Any authentic consideration of pain and its care must acknowledge these realities.

Last updated on: March 7, 2011
First published on: January 1, 2011