Precision, integrative medicine for pain management in sickle cell disease

Abstract

Sickle cell disease (SCD) is a prevalent and complex inherited pain disorder that can manifest as acute vaso-occlusive crises (VOC) and/or chronic pain. Despite their known risks, opioids are often prescribed routinely and indiscriminately in managing SCD pain, because it is so often severe and debilitating. Integrative medicine strategies, particularly non-opioid therapies, hold promise in safe and effective management of SCD pain. However, the lack of evidence-based methods for managing SCD pain hinders the widespread implementation of non-opioid therapies. In this review, we acknowledge that implementing personalized pain treatment strategies in SCD, which is a guideline-recommended strategy, is currently fraught with limitations. The full implementation of pharmacological and biobehavioral pain approaches targeting mechanistic pain pathways faces challenges due to limited knowledge and limited financial and personnel support. We recommend personalized medicine, pharmacogenomics, and integrative medicine as aspirational strategies for improving pain care in SCD. As an organizing model that is a comprehensive framework for classifying pain subphenotypes and mechanisms in SCD, and for guiding selection of specific strategies, we present evidence updating pain research pioneer Richard Melzack's neuromatrix theory of pain. We advocate for using the updated neuromatrix model to subphenotype individuals with SCD, to better select personalized multimodal treatment strategies, and to identify research gaps fruitful for exploration. We present a fairly complete list of currently used pharmacologic and non-pharmacologic SCD pain therapies, classified by their mechanism of action and by their hypothesized targets in the updated neuromatrix model.

Keywords: integrative medicine; pain; pain neuromatrix; precision medicine; sickle cell disease.

Figure 1

Updated neuromatrix model of pain with components. Three types of input, sensory-discriminative, cognitive-evaluative, and motivational-affective, integrate into pain processors. Processing includes perception in midbrain and thalamic brain structures and a network of connections between them, and modulation by these connections and by ascending and descending fibers. Three types of resulting pain reactions include pain perception/sensation, motor function, and stress. Feedback modulates every stage: reactions modulate processing, and processing modulates input signals. Pain intervention targets are suggested by each component. (Adapted from Melzack and numerous authors).

Figure 2

Standard and alternative sickle cell disease pain therapies, and their hypothesized target (s)—sensory-discriminative, cognitive-evaluative, motivational-affective, and pain processing—based on the neuromatrix model of pain. Multiple targets are hypothesized for many therapies.