Optoactivation of locus ceruleus neurons evokes bidirectional changes in thermal nociception in rats

Louise Hickey, Yong Li, Sarah J. Fyson, Thomas C. Watson, Ray Perrins, James Hewinson, Anja G. Teschemacher, Hidemasa Furue, Bridget M. Lumb, Anthony E. Pickering

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Pontospinal noradrenergic neurons are thought to form part of a descending endogenous analgesic system that exerts inhibitory influences on spinal nociception. Using optogenetic targeting, we tested the hypothesis that excitation of the locus ceruleus (LC) is antinociceptive. We transduced rat LC neurons by direct injection of a lentiviral vector expressing channelrhodopsin2 under the control of the PRS promoter. Subsequent optoactivation of the LC evoked repeatable, robust, antinociceptive (+4.7°C ± 1.0, p < 0.0001) or pronociceptive (-4.4°C ± 0.7, p < 0.0001) changes in hindpaw thermal withdrawal thresholds. Post hoc anatomical characterization of the distribution of transduced somata referenced against the position of the optical fiber and subsequent further functional analysis showed that antinociceptive actions were evoked from a distinct, ventral subpopulation of LC neurons. Therefore, the LC is capable of exerting potent, discrete, bidirectional influences on thermal nociception that are produced by specific subpopulations of noradrenergic neurons. This reflects an underlying functional heterogeneity of the influence of the LC on the processing of nociceptive information. © 2014 Hickey et al.

Original languageEnglish
Pages (from-to)4148-4160
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number12
DOIs
Publication statusPublished - 19 Mar 2014

Keywords

  • Animals
  • Hot Temperature
  • Locus Coeruleus
  • Male
  • Neurons
  • Nociception
  • Optogenetics
  • Pain
  • Pain Measurement
  • Rats
  • Rats, Wistar

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