PAF

Although unpleasant, pain has a crucial physiological role warning and prompting the organism to protect the injured area and to reduce general activity waiting for healing. However, sometimes, organisms have to face other dangers as confronting a predator or escaping hostile environments and need to display defensive behaviors. Particularly, acute stress activates neural circuits that produce a strong analgesia, through spinal blockade of nociceptive inputs, a phenomenon called stress-induced analgesia (SIA). Unfortunately, excessive or repeated stress (i.e., PTSD) as well as chronic pain, are capable of modifying stress-pain relationship eliciting a phenomenon called stress induced hyperalgesia (SIH). In the present proposal, we aim at determining the neural circuits involved in the transition from SIA to SIH and deciphering new pertinent targets to treat/improve pathological pain. We propose to use a fear conditioned analgesia paradigm we implemented in the consortium and challenge our paradigm in the context of neuropathic pain with or without fear pathology (i.e, PTSD model). We will then focus on the modulation of such neural circuit by oxytocin that has been shown to be an efficient pain killer modulating all the neural circuits linking fear to pain.