HomeCageScan (HCS) is an automated behavioral scoring system that can be used to classify and quantify rodent behaviors in the home cage. Although HCS has been used for a number of inducible models of severe pain, little has been done to test this system in clinically relevant genetic disease models associated with chronic pain such as Fabry disease. Rats with Fabry disease exhibit mechanical hypersensitivity, however, it is unclear if these rodents also exhibit ongoing non-evoked pain. Therefore, we analyzed HCS data from male and female rats with Fabry disease. Using hierarchical clustering and principal component analysis, we found both sex and genotype differences in several home cage behaviors. Additionally, we used hierarchical clustering to derive behavioral clusters in an unbiased manner. Analysis of these behavioral clusters showed that primarily female Fabry animals moved less, spent less time caring for themselves (e.g., less time spent grooming and drinking), explored less, and slept more; changes that are similar to lifestyle changes observed in patients with long lasting chronic pain. We also show that sniffing, one of the exploratory behaviors that is depressed in Fabry animals, can be partly restored with the analgesic gabapentin, suggesting that depressed sniffing may reflect ongoing pain. Therefore, this approach to HCS data analysis can be used to assess drug efficacy in Fabry disease and potentially other genetic and inducible rodent models associated with persistent pain.