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Pain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine.

ABSTRACT: Chronic pain is highly prevalent, and pain medicine lacks objective biomarkers to guide diagnosis and choice of treatment. The current U.S. "opioid epidemic" is a reminder of the paucity of effective and safe treatment options. Traditional pain diagnoses according to the International Classification of Diseases are often unspecific, and analgesics are often prescribed on a trial-and-error basis. In contrast to this current state of affairs, the vision of future mechanism-based diagnoses of chronic pain conditions is presented in this non-technical paper, focusing on the need for biomarkers and the theoretical complexity of the task. Pain is and will remain a subjective experience, and as such is not objectively measurable. Therefore, the concept of "noci-marker" is presented as an alternative to "pain biomarker", the goal being to find objective, measurable correlates of the pathophysiological processes involved in different chronic pain conditions. This vision entails a call for more translational pain research in order to bridge the gap between clinical pain medicine and preclinical science.

SUBMITTER: Backryd E

PROVIDER: S-EPMC4665549 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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Pain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine.

Bäckryd Emmanuel E

Diagnostics (Basel, Switzerland) 20150317 1

Chronic pain is highly prevalent, and pain medicine lacks objective biomarkers to guide diagnosis and choice of treatment. The current U.S. "opioid epidemic" is a reminder of the paucity of effective and safe treatment options. Traditional pain diagnoses according to the International Classification of Diseases are often unspecific, and analgesics are often prescribed on a trial-and-error basis. In contrast to this current state of affairs, the vision of future mechanism-based diagnoses of chron ...[more]

PMID: 26854144

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Project description:To better understand the relationship between peripheral blood- and brain-based epigenetic activity, we conducted a pilot study on captive baboons (Papio hamadryas) to investigate correlations between miRNA expression in peripheral blood mononuclear cells (PBMCs) and 14 different cortical and subcortical brain regions, represented by two study groups comprised of 4 and 6 animals. Using next-generation sequencing, we identified 362 miRNAs expressed at ≥10 read counts in 80% or more of the brain samples analyzed. Nominally significant pairwise correlations (one-sided P<0.05) between peripheral blood and mean brain expression levels of individual miRNAs were observed for 39 and 44 miRNAs in each group. When miRNA expression levels were averaged across animals within the groups, pairwise correlations between PBMCs and individual brain regions are all highly significant (P<2.2x10^-16), although correlations between brain regions are markedly stronger (rs=0.86-0.99) than those between blood and brain (rs=0.47-0.57). Principal component analysis revealed differentiation in miRNA expression between peripheral blood and the brain regions for the first component (accounting for ~75% of variance). Linear mixed effects modeling attributed most of the variance in expression to differences between miRNAs (>70%), with non-significant 7.5% and 13.1% assigned to differences between blood and brain-based samples in the two study groups. Hierarchical UPGMA clustering revealed two major co-expression branches that are evident in both groups, with one comprised of miRNAs hyper-expressed in blood relative to the brain samples, exhibiting an enrichment of miRNAs expressed in immune cells (CD14+, CD15+, CD19+, CD3+, and CD56+ leukocytes) among the top blood-brain correlates. In the other major branch, hypo-expression in the blood samples was observed, with enrichment for miRNAs associated with Alzheimer’s Disease among its top correlates. Although some differentiation was observed between tissue types, these preliminary findings reveal wider correlated patterns between blood- and brain-expressed miRNAs, suggesting the utility of blood-based miRNA profiling for investigating by proxy the epigenetic underpinnings of neurological and neuroinflammatory processes in the brain.

Dataset Information

Pain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine.

Publications

Pain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine.

Similar Datasets

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