We appreciate the interest of Dr. Tsai et al.  in our recent study of pain medication prescriptions in chronic pain and for advocating for further studies of personalized chronic pain management in clinical practice.

We share the idea of the authors to start evolving the field of personalized chronic pain management care from in-depth biomarker explorations toward assessing the value of specific patient characteristics including both intraindividual and interindividual differences. A biomarker is defined as a characteristic that can be objectively measured as an indicator of healthy or pathologic biologic processes, or pharmacologic responses to therapeutic interventions.  Currently, the field of chronic pain management is still dominated by a unidimensional pain intensity score as marker of the health status or the efficacy of therapeutic interventions. The trends in medication prescription could entail a first step toward a more holistic outcome measure containing both objective and self-reported outcomes into one composite endpoint to serve as indicator of a patients’ health status and reference for the further evaluation of biomarkers in the future. 

With respect to pharmacogenetics, serving as a new approach to drug prescription based on the “personalized-medicine” concept by tailoring treatments to each individual’s genetic/genomic profile, specific genetic variants that influence pharmacokinetics and pharmacodynamics of drugs should be more extensively quantified to better determine effectiveness and/or safety profile of pain drugs, before starting a specific therapy.  Specifically for opioid response, gene variations have been identified that correlate with pain sensitivity, opioid metabolism, and clinical efficacy6  also in acute pain settings.

Yet, as genetics are no dynamic features, they can provide only a picture of the pharmacologic response and/or drug interactions and consequently they are not able to describe the variability of the trajectories of chronic pain and the dynamic response of each patient. Therefore, more recently, genomics is denoted as potential interesting marker,9  able to provide an invaluable biomarker that could vary according to patients and their pain trajectories.  Undoubtedly the patient–physician relationship is vital in settings such as chronic pain since patients often feel isolated, misunderstood, or stigmatized when an underlying cause of pain cannot be identified.  Hence, as genetics can offer a “static” picture of the background of patients (sensibility to pain and responses to drugs), genomics can offer new biomarkers that can also vary according to the clinical response of the patient not only to pain but to all the other multidimensional variables related to this condition. We foresee that, in the near future, epigenetics will play a crucial role in determining the suitability of different types of pain medication when initializing treatment trajectories as well as to create long-term pharmaceutical treatment plans not only according to the predisposition of individual patients in light of polypharmacy, especially in settings with large heterogeneity in presenting phenotypes such as chronic pain, but also according to the specific response that the patient is providing in a specific situation in a specific environment. 

Finally, we think that it should be underlined how genomics, such as proteomics can be useful to understand new pathophysiologic mechanisms both of pain trajectories and drug treatment and to help guiding our treatment even better according to a real individualized pain diagnosis and treatment toward not only “pain relief” but also “care of chronic pain disease.”