Figure 1.

The aim of the BioPain project of the IMI-PainCare consortium is to validate a set of pharmacodynamic biomarkers of nociceptive processing derived from non-invasive measures of nociceptive processing at the peripheral, spinal, brainstem and brain levels. Whereas some biomarkers are selective readouts for a given compartment of the nociceptive system (e.g., small-fibre perception threshold tracking as a readout of nociceptive processing at the level of the peripheral nervous system), other biomarkers are dependent on the state of nociceptive processing along the entire neuraxis (e.g., laser-evoked brain potentials that are sequentially processed and transmitted at peripheral, spinal cord and brain levels). These biomarkers will be tested across four parallel clinical studies (RCT1 [6,11], RCT2 [7,12], RCT3 [8,10] and RCT4 [9]) using three pharmacological probes (lacosamide, pregabalin and tapentadol) that are expected to predominantly affect nociceptive processing at peripheral, spinal and brain levels, respectively. Nonetheless, all three probes are active in multiple compartments. Hence, complex hierarchical modelling and estimation of latent variables will be used in addition to PK-PD modelling.