Starts:

Wednesday, September 21st
4:30pm-6:00pm EDT

Category:

Topical Workshop

Tracks:

Basic Science

Room

716 B

News from the Brainstem: Functional Plasticity in Noradrenergic Nuclei upon Stress and Injury

Multiple lines of evidence demonstrate that one important mechanism underpinning chronic pain is dysfunction of brainstem-origin noradrenergic-control pathways encompassed by the descending pain modulatory system (DPMS). This workshop will detail the latest knowledge regarding the functionality of key noradrenergic nuclei that govern nociceptive processing in health and disease, as we unpick the maladaptive plasticity that initiates, maintains and/or progresses pain states. The locus coeruleus (LC), origin of a traditionally viewed inhibitory component of the descending pain modulatory system, takes centre stage. Beginning with Dr Kirsty Bannister, UK, novel data relating to reciprocity between the LC and other brainstem noradrenergic pathways will be discussed with reference to evidence for a ‘chronic pain generator’ LC role in the switch from health to disease. This will set the scene for Professor Esther Berrocoso, Spain, who will detail data regarding time dependent adaptations produced by nerve injury in LC-brainstem pathways, and their role in sensorial hypersensitivity and affective-related symptoms (anxiety and depression). Finally, in affective terms, Dr Jordan McCall, USA, will discuss the role of LC activity in acute stress-induced antinociception, with special focus on the separation of effects of LC activity that is required during stress, during nociception, or both for stress-induced antinociception.

Presentations

Time
4:30pm EDT6:00pm EDT

Affective and Sensory Disorders in Pain Processing: Higher Brain and Brainstem Circuits that Regulate Pain Inhibition and Facilitation

Tracks: Basic Science
Categories: Topical Workshop

The transition from acute to chronic pain results in maladaptive brain remodeling, as characterized by sensorial hypersensitivity and the ensuing appearance of emotional disorders. I will describe time-dependent plasticity of locus coeruleus (LC) neurons related to the site of injury, ipsilateral (LCipsi) or contralateral (LCcontra) to the lesion. In acute pain, the LC promotes feedback inhibition of nociception due to the activation of the descending pain pathway to the spinal cord. As time passes after injury, endogenous LC analgesia fails, and it promotes pain facilitation through the dorsal reticular nucleus (DRt). Anterior cingulate cortex (ACC) or basolateral amygdala (BLA) activity contributes to anxiety, increasing aversive learning and memory, and behavioral despair, sharing similarities with stress-related disorders. These data demonstrate the functional heterogeneity of the LC output in pain that will be of interest when designing therapeutic strategies. Thus, exogenous activation of the LC→spinal cord projection can relieve pain, while the activation of other structures (prefrontal cortex or BLA) may produce adverse effects.

4:30pm EDT6:00pm EDT

Reciprocity between Brainstem Noradrenergic Nuclei in Health and Disease

Tracks: Basic Science
Categories: Topical Workshop
Presented By: Dr. Kirsty Bannister

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.

4:30pm EDT6:00pm EDT

Stress and the Brainstem: Linking Anti-nociception, Affect and Opioids

Tracks: Basic Science
Categories: Topical Workshop
Presented By: Dr. Jordan G. McCall

Dr. McCall will discuss new findings on how chronic, repeated stress alters endogenous analgesia. In particular the role of high tonic LC activity in acute stress-induced antinociception will be explored with multiple cell-type selective and circuit-level techniques. The temporal dynamics of these effects will be clearly established both in terms of the separation of LC activity that is required during stress, during nociception, or both for stress-induced antinociception and in the context of repeated stress exposures. As many forms of stress-induced antinociception are dependent on endogenous opioids, the role of LC mu opioid receptors is directly assayed in this behavioural paradigm using new mousse lines created for this purpose. Altogether, the presentation will link stress-induced LC activity that is known to drive negative affect to antinociception and identify where these behavioral outputs may diverge.

Presenters

Dr. Kirsty Bannister

Associate Professor
King's College London

Professor Esther Berrocoso

Professor
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación e Innovación Biomédica de Cádiz, Hospital Universitario Puerta del Mar, Cádiz, Spain; Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz, Spain

Dr. Jordan G. McCall

Assistant Professor
Washington University in St. Louis