Human experimental pain models: A review of standardized methods in drug development

Abstract

• Human experimental pain models are essential in understanding the pain mechanisms and appear to be ideally suited to test analgesic compounds. The challenge that confronts both the clinician and the scientist is to match specific treatments to different pain-generating mechanisms and hence reach a pain treatment tailored to each individual patient. Experimental pain models offer the possibility to explore the pain system under controlled settings. Standardized stimuli of different modalities (i.e., mechanical, thermal, electrical, or chemical) can be applied to the skin, muscles, and viscera for a differentiated and comprehensive assessment of various pain pathways and mechanisms. Using a multimodel–multistructure testing, the nociception arising from different body structures can be explored and modulation of specific biomarkers by new and existing analgesic drugs can be profiled. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. Spontaneous pain, the main compliant of the neuropathic patients, but currently there is no human model available that would mimic chronic pain. Therefore, current human pain models cannot replace patient studies for studying efficacy of analgesic compounds, although being helpful for proof-of-concept studies and dose finding.
• Key words: Analgesics, multimodel–multitissue, pain models, proof-of-concept, spontaneous pain