Despite many advances in the last decades in understanding pain, the development of new analgesic compounds has not followed at the same pace. The development of more targeted analgesic compounds... Show moreDespite many advances in the last decades in understanding pain, the development of new analgesic compounds has not followed at the same pace. The development of more targeted analgesic compounds with fewer side effects is therefore essential. With an increased demand to demonstrate pharmacodynamic effects of new analgesic compounds, the importance of human evoked pain models is now higher than ever. Pharmacodynamic evaluation with human evoked pain models offers the possibility to determine the dose ranges at which new analgesics exert their pharmacological effect. Pain models may also aid in the choice of target population, determine which modality of pain a new drug is expected to be most suitable, help to differentiate between a central or more peripheral mode of action of new drugs, and help determine which other effects contribute to its mode of action e.g., sedation. Using pain models in healthy volunteers has important advantages over assessing the effects of new drugs in patients with pain; the pain elicited in human pain models is predictable in its intensity while clinical pain will naturally fluctuate. Analgesic properties can be investigated with pain models without the influence of accompanying symptoms that are often seen in patients with pain. Show less
Drug development scientists are on a search for suitable biomarkers that can assist in predicting the therapeutic potential of analgesic medication and, therefore, it’s efficacy in the target... Show moreDrug development scientists are on a search for suitable biomarkers that can assist in predicting the therapeutic potential of analgesic medication and, therefore, it’s efficacy in the target population. This is particularly appropriate for human pain where models can assist to bridge the preclinical and clinical findings. These models can provide valuable information about the mechanism of action of existing and new drugs. However, a single human pain model cannot be used exclusively to screen the pharmacological mechanism of a compound as it inherently only tests a single mechanism. In this thesis the performance of a battery of pain models (PainCart) was investigated. Three main topics were investigated. (1) The validation of the PainCart was described in which the effects of different classes of analgesics on this battery of pain models were explored. (2) The PainCart was used in different chronic pain populations. (3) The performance of the battery during the development of new analgesic compounds was studied. The battery of pain models can act as biomarker to assess the effect of analgesics on pain. It can be used to benchmark analgesic properties of new drugs against established analgesics in early phase clinical studies. Show less
Yassen, A.; Passier, P.; Furuichi, Y.; Dahan, A. 2013
