Simonds – Salem – Pohida – 2023



Video Monitoring System for Automated Detection of Pain- and Itch- Related Behaviors in Mice

Pain and itch are protective somatosensations that safeguard the organism from toxic environmental factors by producing a desire to scratch or triggering avoidance behaviors. However, both chronic pain and itch can be symptoms of broader systemic illnesses. As many as 20% of the population may suffer from various forms of chronic itch. There are currently few drugs to treat chronic itch, and most are associated with significant side effects, suggesting an urgent need for new types of drugs. Pandey et al recently discovered that R7BP is a master regulator of itch sensation that appears to act by modulating signaling through G protein Gαi/o-coupled kappa opioid receptors (KOR) in the central nervous system [Pandey et al, (2017) PMID 28134655]. Pandey et al demonstrated that R7bp knockout (KO) mice, while otherwise indistinguishable from their wild type littermates, displayed a marked reduction in pruriception (itch sensation) in response to every type of itch-inducing agent tested. Furthermore, the R7bp KO mice exhibited a marked reduction of itch sensitivity in an established model of chronic itch. Pandey et al found that R7bp specifically regulates itch, but not pain, through an intracellular mechanism involving the R7bp-dependent, Gi/o-directed, GTPase-activating protein (GAP)activity of the R7-RGS/ Gβ5 complex.

The discovery suggests that R7bp may be an ideal target for developing novel anti-itch drugs with a broad spectrum of efficacy and with the potential of great specificity, and that inhibition of R7bp-dependent GAP activity should be a highly effective strategy. Drugs targeting R7BP function would represent a brand new therapeutic class. Pharmacologic inhibitors of R7BP function should strongly inhibit itch sensation. This is highly likely based on the behavioral observations in R7bp KO mice cited above and the implication of KOR signaling in the mechanism of R7bp itch regulation as kappa opioid agonists are known to inhibit itch sensation in both mice and humans. Drugs inhibiting R7BP function can be offered for the relief of patients with uremia, liver, skin, and other diseases associated with chronic, pathologic itch.

One of the obstacles that hinders the development of R7bp inhibitors is the lack of efficient methods to quantify scratch behaviors in mice in the research environment. It typically takes 30 to 60 minutes to complete scratch quantification and behavioral testing of a single mouse exposed to an itch-inducing agent.  Currently the quantification and recording of mouse scratching behavior are mostly conducted manually either by an observer directly in real time or through subsequent viewing the prior session recordings. This process is very tedious, labor intensive, and time consuming and is also prone to operator-dependent variance when different observers are involved.

This project is to develop a device and associated software that can automatically record and count scratches of mice in response to different drug treatments so that quantification of mouse scratches can be more objective, reliable and less labor intensive. The success of this project would greatly facilitate the development of R7bp inhibitors.  Additionally, this device can also be broadly used for any scratch-related or pain-avoidance behavioral tests and should provide great benefit to both research communities and pharmaceutical companies.

A BESIP student working on this project should have an interest in animal-based research, image and video analysis, and biomedical instrumentation. Working closely with the interdisciplinary team, the intern could help install several of the monitoring units in Dr. Simonds lab, complete with control PC and software.  The intern will acquire video with the units.  The intern will conduct test experiments to identify behavioral differences in different strains of mice. The experiments might require hardware modification to the base units, which would require the intern to work with 3D CAD for design and fabrication of modifications.  The intern will work closely with Endocrine Signaling and Oncogenesis Section staff to leverage their expertise in identifying behaviors of interest, such as different scratching/itching movement, in video.  The intern will work closely with SPIS staff to process the video to extract relevant measures of activity and detect behavioral patterns of interest. Lastly, actual experiments for detecting itch and pain related behavior will be carried out and the intern will process the experiments and report the scientific results.  Throughout the process, the intern will identify areas of improvement in both the hardware and software (including user interfaces) and work towards improving the ease-of-use and reliability of the system as a whole.
Simonds lab: Expertise in studying itch- and pain- associated mouse behaviors and their molecular mechanisms.   Lab members will contribute their expertise in mouse management and testing for both itch and pain behaviors.   The lab will provide all the required facilities, space, chemicals and other necessary materials required for testing the automated video monitoring system.  The lab will also assist in video annotation and analysis for optimizing the detection accuracy of the novel device.  

Pohida lab: Provides electrical, electronic, electro-optical, mechanical, computer, and software engineering expertise to NIH projects that require in-house technology development. Collaborations involve advanced signal transduction and data acquisition; real-time signal and image processing; control and monitoring systems (e.g., robotics and process automation); and rapid prototype development. Collaborations result in the design of first-of-a-kind biomedical/clinical research systems, instrumentation, and methodologies.