Characterization and re-evaluation of experimental pain models in healthy subjects

Siebenga, P.S. (2020)

Doctoral Thesis

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 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.

• Analgesics
• Human evoked pain models
• Neuropathic pain
• Nociceptive pain
• Pharmacodynamics
• Phase-1 clinical triala

• All authors: Siebenga, P.S.
• Supervisor: Cohen, A.F.
• Co-supervisor: Groeneveld, G.J.
• Committee: Dahan, A.; Evers, A.E.W.; Jongen, J.L.M.; Lange, E.C.M. de
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2020-03-04