MCP-Mod has been proposed as analysis method for investigating the dose-response (DR) relationship and dose finding in clinical Phase II trials. The original methodology as well as several generalizations are well accepted by Health Authorities. In this paper, we investigate the application of the generalized MCP-Mod approach in chronic pain, a challenging therapeutic area with primary endpoints based on patient reported outcomes, repeatedly measured over time, with high inter-subject variability and potentially high premature discontinuation rates. In a simulation study, we investigate the impact of several study design factors on the ability to establish proof of concept, to derive information on the functional DR relationship, and to estimate target doses of interest (eg, ED80). Furthermore, different methods to derive confidence intervals for the target doses of interest are compared regarding their coverage rates and widths. Proof of concept is well established by MCP-Mod even in longitudinal trials with high inter-subject variability. While the most reasonable DR model is also selected in most cases, estimated target doses and their bootstrap confidence intervals have to be treated with some caution, if trial data are strongly affected by individual heterogeneity as observed in two recent chronic pain trials. We describe encountered challenges and provide recommendations for designing future dose ranging longitudinal trials with high inter-subject variability under model uncertainty.