Revealing novel signatures of pathological pain through next-generation behavioral sequencing and awake rs-fMRI

With symptoms such as spontaneous pain, allodynia and or hyperalgesia, chronic pain affects more than 1.5
billion people worldwide and accounts for about 20% of physician visits. Yet, up to two-thirds of patients are
unsatisfied with current treatments. Despite relentless pharmacological efforts and major scientific advances in
our understanding of how the brain orchestrates coping behavioral mechanisms in response to pathological
pain, this past decade has been marked by an increasing number of failing clinical trials. Interestingly, current
pain behavioral and neuroimaging studies present tremendous potential in terms of translational diagnostic,
prognostic and or treatment-response tools. However, many technical obstacles. First, while humans can
verbally describe their pain, studies on rodents have long relied on behavioral assays providing non-exhaustive
characterization or altering animals’ original sensitivity through repetitive stimulations. Second, the variability
across chronic pain patients and conditions makes it challenging to understand functional brain dynamic
alterations supporting pain chronification or resolution. While pain duration varies according to the initial cause
of tissue injury, there is no rigorously controlled study establishing both semiology- and etiology-specific
dynamic brain signatures for the transition from acute to chronic pain. In line with this, most preclinical pain
neuroimaging studies are performed on anesthetized laboratory animals, which is a confound considering the
analgesic effect of anesthetics. Such caveats render correlations between chronic pain as a disease and inherent
behavioral and real-time brain activity alterations, challenging. Here I present emerging videography and
computational-based behavioral approaches that have the potential to significantly improve preclinical pain
research. Lastly, through a preliminary study, I show how the unprecedented longitudinal coupling of behavior
and awake resting-state fMRI in head-fixed mice, can unravel novel anatomical targets for the treatment of long-
lasting pain.