Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment

Tracey, Irene; Woolf, Clifford J.; Andrews, Nick

doi:10.1016/j.neuron.2019.02.019

Cited by 162 publications

(161 citation statements)

References 181 publications

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“…In contrast, the RPN-signature is based on brain activity measured in the absence of any ongoing painful experience (which we refer to as pain-free resting-state). Therefore, it introduces a conceptually new modality for future efforts of building a composite pain biomarker 27 .…”

Section: Discussionmentioning

confidence: 99%

“…In sum, the RPN-signature identified here has the potential to become a novel, non-invasive neuromarker for the supraspinal neural contribution to pain sensitivity, which is of interest in clinical pain states and especially in translational research and development of analgesic treatment strategies, where uncoupling peripheral and central mechanisms is often of crucial interest. Moreover, the RPN-signature might serve as a novel, resting network-based building block in a future pain biomarker composite signature 27 .…”

Section: Discussionmentioning

confidence: 99%

“…However, due to the small sample sizes, highly varying methodology (e.g. regarding the correction of physiological and motion artefacts) and the lack of validation in these previous studies the predictive power and clinical relevance of this kind of resting-state brain activity remains unclear to date 27 .…”

mentioning

confidence: 98%

“…Finally, and most importantly, a robust, generalizable and rigorously validated prediction of pain sensitivity-based on the resting-state network of pain sensitivity-could lay the foundations for a non-invasive neuromarker of an individual's sensitivity to pain. Such a resting brain network-based biomarker could contribute to the development of a future pain biomarker composite signature 27 that could aid the assessment of an individual's risk of developing pain, and the objective characterization of pain conditions and analgesic treatment effects in experimental and clinical pain research.…”

mentioning

confidence: 99%

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Pain-free resting-state functional brain connectivity predicts individual pain sensitivity

Spisák¹,

Kincses

Schlitt³

et al. 2020

Nat Commun

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Individual differences in pain perception are of interest in basic and clinical research as altered pain sensitivity is both a characteristic and a risk factor for many pain conditions. It is, however, unclear how individual sensitivity to pain is reflected in the pain-free resting-state brain activity and functional connectivity. Here, we identify and validate a network pattern in the pain-free resting-state functional brain connectome that is predictive of interindividual differences in pain sensitivity. Our predictive network signature allows assessing the individual sensitivity to pain without applying any painful stimulation, as might be valuable in patients where reliable behavioural pain reports cannot be obtained. Additionally, as a direct, non-invasive readout of the supraspinal neural contribution to pain sensitivity, it may have implications for translational research and the development and assessment of analgesic treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Pain-free resting-state functional brain connectivity predicts individual pain sensitivity

Spisák¹,

Kincses

Schlitt³

et al. 2020

Nat Commun

View full text Add to dashboard Cite

show abstract

“…What are the clinical implications? One obvious problem in pain research is the lack of suitable biomarkers and objective measures of pain-especially possible malfunctions of the pain pathway in the primary afferent neuron in the pain pathway [43]. Thus, imaging of the DRG could fill this gap in certain painful conditions.…”

Section: Discussionmentioning

confidence: 99%

Regional Differences in Tight Junction Protein Expression in the Blood–DRG Barrier and Their Alterations after Nerve Traumatic Injury in Rats

Ben-Kraiem

Blum

et al. 2019

IJMS

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The nervous system is shielded by special barriers. Nerve injury results in blood–nerve barrier breakdown with downregulation of certain tight junction proteins accompanying the painful neuropathic phenotype. The dorsal root ganglion (DRG) consists of a neuron-rich region (NRR, somata of somatosensory and nociceptive neurons) and a fibre-rich region (FRR), and their putative epi-/perineurium (EPN). Here, we analysed blood–DRG barrier (BDB) properties in these physiologically distinct regions in Wistar rats after chronic constriction injury (CCI). Cldn5, Cldn12, and Tjp1 (rats) mRNA were downregulated 1 week after traumatic nerve injury. Claudin-1 immunoreactivity (IR) found in the EPN, claudin-19-IR in the FRR, and ZO-1-IR in FRR-EPN were unaltered after CCI. However, laser-assisted, vessel specific qPCR, and IR studies confirmed a significant loss of claudin-5 in the NRR. The NRR was three-times more permeable compared to the FRR for high and low molecular weight markers. NRR permeability was not further increased 1-week after CCI, but significantly more CD68+ macrophages had migrated into the NRR. In summary, NRR and FRR are different in naïve rats. Short-term traumatic nerve injury leaves the already highly permeable BDB in the NRR unaltered for small and large molecules. Claudin-5 is downregulated in the NRR. This could facilitate macrophage invasion, and thereby neuronal sensitisation and hyperalgesia. Targeting the stabilisation of claudin-5 in microvessels and the BDB barrier could be a future approach for neuropathic pain therapy.

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Axonal Excitability Does Not Differ between Painful and Painless Diabetic or Chemotherapy‐Induced Distal Symmetrical Polyneuropathy in a Multicenter Observational Study

Themistocleous

Kristensen

Solà³

et al. 2022

Annals of Neurology

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Objective: Axonal excitability reflects ion channel function, and it is proposed that this may be a biomarker in painful (vs painless) polyneuropathy. Our objective was to investigate the relationship between axonal excitability parameters and chronic neuropathic pain in deeply phenotyped cohorts with diabetic or chemotherapy-induced distal symmetrical polyneuropathy. Methods: Two hundred thirty-nine participants with diabetic polyneuropathy were recruited from sites in the UK and Denmark, and 39 participants who developed chemotherapy-induced polyneuropathy were recruited from Denmark. Participants were separated into those with probable or definite neuropathic pain and those without neuropathic pain. Axonal excitability of large myelinated fibers was measured with the threshold tracking technique. The stimulus site was the median nerve, and the recording sites were the index finger (sensory studies) and abductor pollicis brevis muscle (motor studies). Results: Participants with painless and painful polyneuropathy were well matched across clinical variables. Sensory and motor axonal excitability measures, including recovery cycle, threshold electrotonus, strength-duration time constant, and current-threshold relationship, did not show differences between participants with painful and painless diabetic polyneuropathy, and there were only minor changes for chemotherapy-induced polyneuropathy. Interpretation: Axonal excitability did not significantly differ between painful and painless diabetic or chemotherapyinduced polyneuropathy in a multicenter observational study. Threshold tracking assesses the excitability of myelinated axons; the majority of nociceptors are unmyelinated, and although there is some overlap of the "channelome" between

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Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment

Cited by 162 publications

References 181 publications

Pain-free resting-state functional brain connectivity predicts individual pain sensitivity

Pain-free resting-state functional brain connectivity predicts individual pain sensitivity

Regional Differences in Tight Junction Protein Expression in the Blood–DRG Barrier and Their Alterations after Nerve Traumatic Injury in Rats

Axonal Excitability Does Not Differ between Painful and Painless Diabetic or Chemotherapy‐Induced Distal Symmetrical Polyneuropathy in a Multicenter Observational Study

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