Fabry Rat Home Cage Behaviors Reveal an Ongoing Pain Phenotype

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 validate this system in clinically relevant genetic disease models associated with chronic pain such as Fabry disease. It is also unclear if male or female rodents exhibit distinct behavioral phenotypes during ongoing pain. Therefore, we analyzed HCS data from male and female rats with Fabry disease to determine if these rats exhibited ongoing pain. Using 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 Fabry animals exhibited lifestyle changes similar to that seen in patients, which includes moving less, spending less time caring for themselves, exploring less, and sleeping more. Sniffing, one of the exploratory behaviors that is depressed in Fabry animals can be partly restored with the analgesic gabapentin, indicating it may be tied to ongoing pain in our rodent model. Therefore, this approach to HCS data analysis can be used to assess analgesic drug efficacy in Fabry disease and potentially other genetic and inducible models with persistent, ongoing pain. Grant support from (NIH) R37 NS108278-02 (CLS), NIH RO1 NS070711-11 (CLS), NIH HL122358 (MRH), and NIH DK122647 (AM).