Reciprocity between Brainstem Noradrenergic Nuclei in Health and Disease

The aim of the presentation described herein is to inform the audience on the nature of the influence of the locus coeruleus (LC), a noradrenergic brainstem nucleus traditionally viewed as an inhibitory component of the descending pain modulatory system (DPMS), on spinal nociceptive processing. Recognising that ventral, but not dorsal, LC neurons project to the dorsal horn, the modular organisation of the LC lends itself to pain modulatory (inhibitory as well as facilitatory) mechanisms in the transition from acute to chronic pain. Interestingly, the mechanistic underpinning of this contrasting modulatory impact likely involves separate projection sites to key medullary nuclei that themselves govern distinct modulatory controls. Pinpointing the functionality of discrete top-down pathways is crucial for understanding the sensorimotor modulation in health (i.e. nociception) and disease (i.e. chronic pain). Thus, I will discuss changes in the reciprocity of noradrenergic nuclei governance, where tonic as well as evoked modulatory pathways will be considered (LC-spinal as well as DNIC circuits respectively), in animal models of chronic pain including neuropathy and cancer induced bone pain, where stage specific treatment approaches are crucial if pain is to be managed along the course of the disease.