Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs

Niculescu, Alexander B.; Le-Niculescu, Helen; Levey, Daniel F.; Roseberry, K.; Soe, Katherine; Rogers, Jesse D.; Khan, Fuad; Jones, Thaon; Judd, Suzanne E.; McCormick, M. A.; Wessel, A. R.; Williams, Amanda L.; Kurian, Sunil M.; White, Fletcher A.

doi:10.1038/s41380-018-0345-5

Cited by 75 publications

(71 citation statements)

References 43 publications

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“…A recent study by Niculescu et al (2019) examined blood biomarkers and their association with pain in psychiatric patients using a whole-genome approach at the mRNA level. 16 They identified a set of biomarkers with a predictive capacity for future pain and emergency department (ED) visits for pain. An interesting finding from this study includes the fact that future ED visits were better predicted by the biomarkers in independent cohorts compared to other clinical markers, such as the visual analogue scale (VAS), that are typically used.…”

Section: Discussionmentioning

confidence: 99%

<p>Applying Serum Cytokine Levels to Predict Pain Severity in Cancer Patients</p>

Fazzari

Sidhu

Motkur

et al. 2020

JPR

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Background and Aim: Cancers originating in the breast, lung and prostate often metastasize to the bone, frequently resulting in cancer-induced bone pain that can be challenging to manage despite conventional analgesic therapy. This exploratory study's aim was to identify potential biomarkers associated with cancer-induced pain by examining a sample population of breast cancer patients undergoing bisphosphonate therapy. Methods: A secondary analysis of the primary study was performed to quantify serum cytokine levels for correlation to pain scores. Cytokines with statistically significant correlations were then input into a stepwise regression analysis to generate a predictive equation for a patient's pain severity. In an effort to find additional potential biomarkers, correlation analysis was performed between these factors and a more comprehensive panel of cytokines and chemokines from breast, lung, and prostate cancer patients. Results: Statistical analysis identified nine cytokines (GM-CSF, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-12p70, IL-17A, and IL-23) that had significant negative correlations with pain scores and they could best predict pain severity through a predictive equation generated for this specific evaluation. After performing a correlation analysis between these factors and a larger panel of cytokines and chemokines, samples from breast, lung and prostate patients showed distinct correlation profiles, highlighting the clinical challenge of applying pain-associated cytokines related to more defined nociceptive states, such as arthritis, to a cancer pain state. Conclusion: Exploratory analyses such as the ones presented here will be a beneficial tool to expand insights into potential cancer-specific nociceptive mechanisms and to develop novel therapeutics.

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Section: Discussionmentioning

confidence: 99%

<p>Applying Serum Cytokine Levels to Predict Pain Severity in Cancer Patients</p>

Fazzari

Sidhu

Motkur

et al. 2020

JPR

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“…Considering that opioid receptors and lymphocytes activity could be influenced by opioid treatment [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35], patients currently being treated with opioids were not enrolled. However, information about the assumption of pharmacological therapy was collected.…”

Section: Participantsmentioning

confidence: 99%

“…Metabolomics analysis through the innovative technique called "vibrational spectroscopy" [16] has detected a "molecular fingerprint" in blood samples, specific for FM patients. More recently, Niculescu and colleagues [26] have proposed putative "risk genes", showing a higher expression, and putative "protective/resilience genes", with a lower expression, in severe pain states. In recent years, attention has been focused on the close association between peripheral nerve and opioid-containing immune cells [27].…”

Section: Introductionmentioning

confidence: 99%

Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases

Raffaeli

Malafoglia

Bonci

et al. 2020

IJMS

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Fibromyalgia (FM) diagnosis follows the American College of Rheumatology (ACR) criteria, based on clinical evaluation and written questionnaires without any objective diagnostic tool. The lack of specific biomarkers is a tragic aspect for FM and chronic pain diseases in general. Interestingly, the endogenous opioid system is close to the immune one because of the expression of opioid receptors on lymphocytes membrane. Here we analyzed the role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM and osteoarthritis (OA) patients. We enrolled three groups of females: FM patients, OA patients (chronic pain control group) and healthy subjects (pain-free negative control group). We collected blood samples to apply immunophenotyping analysis. Written tests were administrated for psychological analysis. Data were statistically analyzed. Final results showed that the percentage of Mu-positive B cells were statistically lower in FM and OA patients than in pain-free subjects. A low expression of Mu-positive B cell was not associated with the psychological characteristics investigated. In conclusion, here we propose the percentage of Mu-positive B cells as a biological marker for an objective diagnosis of chronic pain suffering patients, also contributing to the legitimacy of FM as a truly painful disease.

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“…Management of NMOU can be challenging for physicians because there are no accurate biomarkers for determining patients’ pain experience. Although electroencephalogram, functional magnetic resonance imaging, and gene expression biomarkers show some promise, these evaluations are in their infancy. There are currently no guidelines for the management of NMOU in patients with cancer‐related pain; however, clinicians are encouraged to adopt universal precautions (UPs) as their clinical framework for managing cancer pain (Table ).…”

Section: Managementmentioning

confidence: 99%

Best Practices in the Management of Nonmedical Opioid Use in Patients with Cancer-Related Pain

Ulker

Fabbro

2019

The Oncologist

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Introduction Nonmedical opioid use (NMOU) in patients with cancer is a term covering a spectrum of nonprescribed opioid use. The extent to which an individual uses opioids in a nonprescribed manner will influence propensity for adverse effects such as neurotoxicity, substance use disorder, overdose, and death. Objectives The objectives of this study were to (A) evaluate current literature regarding management of NMOU in patients with cancer‐related pain; (B) provide best practice recommendations based on evidence; and (C) integrate practices derived from the management of noncancer pain, where clinically appropriate or when the oncology literature is limited. Methods This study is a narrative review. Implications Although harm from NMOU was thought to be rare among oncology patients, about one in five patients with cancer is at risk of adverse outcomes including prolonged opioid use, high opioid doses, and increased health care utilization. The management of NMOU can be challenging because pain is a multidimensional experience encompassing physical, psychological, and spiritual domains. An interdisciplinary team approach is most effective, and management strategies may include (A) education of patients and families; (B) harm reduction, including opioid switching, decreasing the overall daily dose, avoiding concurrent sedative use, and using adjuvant medications for their opioid‐sparing potential; (C) managing psychological and spiritual distress with an interdisciplinary team and techniques such as brief motivational interviewing; and (D) risk mitigation by pill counts, frequent clinic visits, and accessing statewide prescription drug monitoring plans. Conclusion Although many of the management strategies for NMOU in patients with cancer‐related pain are modeled on those for chronic non–cancer‐related pain, there is emerging evidence that education and harm‐reduction initiatives specifically for cancer‐related pain are effective. Implications for Practice Nonmedical opioid use (NMOU) in patients with cancer is a term covering a broad spectrum of nonprescribed opioid use. The extent to which an individual uses opioids in a nonprescribed manner will influence propensity for adverse effects such as neurotoxicity, substance use disorder, overdose, and death. This review evaluates the evidence for best practices in oncology and addresses limitations in the literature with supplemental evidence from noncancer chronic pain. Management recommendations for NMOU are provided, based on a combination of literature‐based evidence and best clinical practice. Effective management of NMOU in oncology has the potential to improve quality of life, decrease health utilization, and improve survival.

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Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs

Cited by 75 publications

References 43 publications

<p>Applying Serum Cytokine Levels to Predict Pain Severity in Cancer Patients</p>

<p>Applying Serum Cytokine Levels to Predict Pain Severity in Cancer Patients</p>

Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases

Best Practices in the Management of Nonmedical Opioid Use in Patients with Cancer-Related Pain

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