PAIN-INDUCED MODULATION OF RELAXIN-3 NEURONS IN THE NUCLEUS INCERTUS

Chronic pain is a major health issue, affecting around 25% of the world population, it generates medical cost, daily life burden, and is related to psychiatric comorbidites (e.g. anxiety and depression). Modulation of pain by neuropeptides in the brain is poorly described. Our preliminary results in rodents indicate an analgesic role of the relaxin-3 neuropeptide, already known for its anxiolytic and antidepressant effects. The majority of relaxin-3 positive neurons are located in the nucleus incertus, a pontine nucleus. Those neurons project to cortical and subcortical areas that are part of the pain matrix (e.g. anterior cingulate cortex, amygdala). The aim is to study how the relaxin-3 system is modulated by chronic pain. For this purpose, we used in vivo electrophysiology in the nucleus incertus during nociceptive stimuli in control and in a model of persistent inflammation. Then, we performed retrograde tracing to identify the pain matrix regions projecting to nucleus incertus’ relaxin-3 neurons. This will unravel a novel role of the nucleus incertus in pain circuits. Our results showed that nucleus incertus' neurons respond to both mechanical and thermal nociceptive stimuli, with either activation or inhibition at time of the stimulus. Retrograde tracing showed nucleus incertus projecting regions in ascending and descending pain pathways (e.g. anterior cingulate cortex, thalamus, periaqueductal gray). These data highlight the role of the relaxin-3 neurons of the nucleus incertus in the pain pathways, reinforcing the interest to target this peptidergic system for therapeutic intervention in persistent pain condition.