Back Translation of Functional, Pharmacodynamic Pain Biomarkers into Rodents

As part of the BioPain subtopic of IMI-PainCare, multiple pharmacodynamic (PD) biomarkers of nociceptive system function are being back translated from humans to rodents and their translatability assessed, specifically in relation to the effects elicited by the administration of three model compounds (lacosamide, pregabalin & tapentadol). Four primary assays are being utilized in this project: peripheral nerve excitability testing (threshold tracking), ii) somatosensory-evoked, spinal potentials (N13 response), (iii) EEG ± laser-evoked potentials (LEPs) and (iv) functional magnetic resonance imaging (fMRI). Here we will provide an overview of this effort, with a specific focus on comparisons between human and rodent LEPs. In brief, our work demonstrates that LEPs with features comparable to those recorded in humans can be reliably recorded in awake, freely-moving rats. Administration of the three model compounds significantly reduces their amplitude, with a temporal profile consistent with each drugs PK profile. The compounds also modulate concurrently recorded resting state spectral power and auditory evoked potential amplitude, providing additional insights into non-specific effects of the compounds on CNS function (e.g. sedation). With the aid of extensive PK and PD profiles generated for each compound (including within-subject PK & PD), we will present the PK-PD relationships describing these pharmacological effects.