A NOVEL ROLE OF THE DESCENDING ANALGESIA SYSTEM IN THE REGULATION OF VAGAL REFLEXES

Abstract

The submedius nucleus of the thalamus (SubM), ventrolateral orbital cortex (VLO) and periaqueductal grey (PAG) constitute a well‐described pain modulatory pathway. Activation leads to depression of nociceptive inputs in the spinal cord via the rostromedial medulla and brainstem descending inhibitory systems. Using transynaptic anterograde viral tracing we noted a neural circuit derived from jugular ganglia vagal afferents innervating the respiratory tree projecting to the SubM, suggestive that vagal afferent pathways may be regulated by SubM‐VLO‐PAG descending modulatory system. In functional studies using urethane anesthetized Sprague Dawley rats, electrical stimulation of the larynx to activate vagal afferent fibres evoked respiratory slowing in a stimulus frequency dependent manner. Concomitant SubM activation via microinjections of 5 ug serotonin significantly inhibited reflex reductions in respiration when compared to vehicle controls (e.g., baseline respiratory rate of 117±4.7 breaths per minute (bpm), to 12±2.2 bpm and 69±5.9 bpm in vehicle and serotonin animals, respectively; p=0.0001, n=9/group). Chemogenetic activation of the SubM with the Gq‐DREADD demonstrated a similar inhibitory effect on respiratory slowing (86±7.6 bpm and 15±62.4 bpm in +m3D+1 mg/kg CNO and –m3D+1 mg/kg CNO animals, respectively; p=0.0001, n=3/group). This inhibitory effect was absent in animals receiving prior electrolytic lesion of the VLO. Moreover, lesion of the VLO facilitated respiratory slowing caused by laryngeal stimulation (6±6.6 bpm and 73.5±6.7 bpm in lesion and sham animals, respectively; p=0.0001, n=5/group), consistent with a tonic descending inhibitory influence over respiratory vagal afferent processing. Taken together, these data support the notion that the SubM‐VLO‐PAG descending modulatory system plays an import role in the regulation of bulbar visceral afferent processing.Support or Funding InformationA McGovern a a current recipient of a Peter Doherty Fellowship (National Health and Medical Research Council, Australia).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.