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.