Kobayashi K, Winberry J, Liu CC, Treede RD, Lenz FA. A painful cutaneous laser stimulus evokes responses from single neurons in the human thalamic principal somatic sensory nucleus ventral caudal (Vc). J Neurophysiol 101: 2210 -2217, 2009. First published February 25, 2009 doi:10.1152/jn.91347.2008. Cutaneous application of painful radiant heat laser pulses evokes potentials (laserevoked potentials) that can be recorded from scalp or intracranial electrodes. We have now tested the hypothesis that the response of thalamic neurons to a cutaneous laser stimulus occurs at latencies predicted by the conduction delay between the periphery and the thalamus. We have carried out recordings from human thalamic neurons in the principal sensory nucleus (ventral caudal) in patients undergoing awake surgery for the treatment of tremor. The results demonstrate that many neurons respond to the laser with early and/or late latency peaks of activity, consistent with conduction of the response to the laser stimulus through pathways from A␦ and C fibers to the thalamus. These peaks were of short duration, perhaps due to the somatotopic-and modality-specific arrangements of afferent pathways to the thalamus. The responses of these thalamic neurons to the laser stimulus sometimes included low-threshold spike (LTS) bursts of action potentials, consistent with previous studies of different painful stimuli. A prior study has demonstrated that spike trains characterized by common LTS bursts such as the intermediate (I) category spontaneously change their category more commonly than do those without LTS bursts (NG: nongrouped category) during changes in the cognitive task. Spike trains of laser-responsive neurons were more common in the I category, whereas those of laser nonresponsive neurons were more common in the NG category. Therefore neuronal spike trains in the I category may mediate shifts in endogenous or cognitive pain-related behavior.