Preclinical investigative models of pain generally measure only changes in reflexive response thresholds in rodents following application of a standardized noxious mechanical, thermal or chemical stimulus. Human interpretation of behavioral responses to observer-applied stimuli are inherently subject to observer bias, anthropomorphization, and other confounders. Furthermore, the translational relevance of such changes in stimulus-evoked pain thresholds is limited since spontaneous pain - characterized by ongoing pain in absence of an overt stimulus - is, by far, the most common pain-related clinical complaint. My goal is to explore neurobiological mechanisms that underlie ongoing or spontaneous pain. The primary problem though, is how to measure what an animal is feeling. The central hypothesis of my proposed study is that observer-independent monitoring of voluntary behavior in rodents will provide an objective readout reflecting the presence of ongoing or paroxysmal pain. This hypothesis was formulated, in part, based on recent observations from the Woolf lab that the functional changes produced by inflammation can be monitored by observing changes in voluntary wheel running behavior in mice, and that these behavioral changes are much more sensitive to analgesic drug effects than traditional reflexive measures. I now plan to utilize novel methods that I have developed for automated real-time recording and analysis of animal behavior using infrared frustrated total internal reflectance (IR-FTIR) touchscreen technology. I will employ this technique to identify pain-related changes in a broad range of rodent behaviors including posture, grooming, social behaviors, ambulation, limb position, and gait. I will measure changes in the freely moving behavioral repertoire in models of peripheral inflammation, test their sensitivity to known-effective analgesics, and determine the consequence on these behaviors, of treatment with anti-inflammatory and opiate compounds.
Ongoing pain in the absence of a known stimulus is a cardinal feature of most chronic pain syndromes. Preclinical investigative pain assays, however, are largely reliant on acute, stimulus-evoked pain measures that are a poor surrogate for the human experience of chronic pain. This project aims to identify changes in voluntary mouse behavior that reflect ongoing pain and to apply observer-independent methods to characterize and analyze these behaviors.
