Starts:

Tuesday, September 20th
10:45am-12:15pm EDT

Category:

Topical Workshop

Tracks:

Novel Experimental/Analytic Approaches/Tools

Room

718 B

Functional Biomarkers of Nociceptive Signal Processing – Back-translation of Human Studies to Preclinical Models

There is a great need for functional biomarkers of nociceptive signal processing and pain translating from animals to humans. Drugs that are efficacious analgesics in preclinical models often prove to have negligible clinical efficacy. For more efficient analgesic development, robust translational measures are needed that can unequivocally prove that a drug has bound to and engaged the target of interest at high enough levels to have a biologically meaningful effect. In this workshop we will present how analgesic drug efficacy is tested in animal models and the main gaps in these preclinical models. We will show the main neurophysiological and neuroimaging biomarkers and provide evidence of their usefulness to assess and quantify nociceptive signal processing and pain. More specifically, we will show how spinal cord and brainstem excitability investigations in humans (i.e. N13 component of the somatosensory evoked potentials, the nociceptive RIII reflex and the R2-blink reflex recovery cycle) reliably reflect dorsal horn and brainstem excitability changes due to central sensitization. We will provide evidence that functional neuroimaging can be used for assessing how the different drugs affect specific brain areas and how treatment-induced brain changes could be used to make generalizable inferences about pain relief.

Presentations

Time
10:45am EDT12:15pm EDT

Functional Markers of Nociceptive Processing and Central Sensitization for Pre-clinical and Clinical Drug Development

Tracks: Novel Experimental/Analytic Approaches/Tools
Categories: Topical Workshop
Presented By: Prof. André Mouraux

Currently available pharmacological therapies provide inadequate relief for many patients with chronic pain. Novel drugs which are efficacious analgesics in preclinical models often have little or no clinical efficacy, but it is often not known whether the drug engaged the human target sufficiently to have a meaningful pharmacodynamic effect. To address this issue Regulatory Agencies are recommending the development and use of objective biomarkers of nociceptive processing to improve the development of drugs for chronic pain. Unfortunately, objective measures for quantifying central sensitization, a key mechanism for chronic pain, are lacking.
This presentation will provide information on how psychophysical, electrophysiological and neuro-imaging biomarkers might be used to build a quantitative understanding between drug exposure and target engagement.
In this presentation we will also describe back-translational biomarkers for bridging animal and human studies, and describe how the development of functional biomarkers of central sensitization could accelerate the development of novel analgesics in several ways: preclinical prediction could be improved by using translatable readouts across species; clinical Phase 1 trials could benefit from biomarkers of target engagement and from human surrogate models predictive of clinical efficacy; clinical Phase 2 and 3 studies could benefit from tools for patient stratification.

10:45am EDT12:15pm EDT

Functional Neuroimaging and Psychophysics as Potential Biomarkers of Chronic Pain and Predictors of Treatment Outcome

Tracks: Novel Experimental/Analytic Approaches/Tools
Categories: Topical Workshop
Presented By: Dr. Karen D. Davis

In this presentation I will describe how functional neuroimaging (fMRI, MEG) and psychophysics can be used to study abnormalities in patients with chronic pain.

I will also show that functional neuroimaging and psychophysics might contribute to the development of predictive measures of treatment outcomes. As one example, I will present findings in patients with refractory neuropathic pain, that pre-treatment level of temporal summation of pain as well as dynamic functional connectivity of the default mode network within the descending antinociceptive pathway might predict the pain relief effect of ketamine.

10:45am EDT12:15pm EDT

Neurophysiological Biomarkers for Central Sensitization in Humans

Tracks: Novel Experimental/Analytic Approaches/Tools
Categories: Topical Workshop

Although different experimental pain models have been devised to investigate the mechanisms underlying central sensitization in humans, how to reliably quantify central sensitization within the dorsal horn of the human spinal cord is still an issue of controversy.

Within the IMI-PainCare project (IMIPAINCARE Grant number 777500) we are testing different neurophysiological measures to assess spinal and brainstem excitability and verifying how central sensitization induced by capsaicin and high frequency stimulation modulates these neurophysiological responses.

In this presentation I will show our recent experimental data in humans. These data have now provided evidence that the N13 component of somatosensory evoked potentials (N13 SEP), the RIII flexion reflex and the recovery cycle of the R2 blink reflex reflect dorsal horn excitability changes associated with central sensitization phenomenon. I will also show our parallel preclinical research activity currently verifying whether these neurophysiological measures might be reliably applied in animals, in order to assess dorsal horn excitability. This back-translation from humans to animals of reliable measure of central sensitization might be useful to improve drug selection in preclinical studies.

Presenters

Professor Andrea Truini

Professor of Neurology
University Sapienza

Dr. Karen D. Davis

Professor and Senior Scietist
University of Toronto and Krembil Brain Institute

Prof. André Mouraux

Professor
Université Catholique de Louvain (UCLouvain)