Reply Understanding of Human Pain in the Brain Through Topographic Mapping and Quantification of Laser-Evoked Potentials An Integration Andrew C. N. Chen, * Lars Arendt-Nielsen, t and Leon PlaghkFt I n this short synopsis, we wish to express that the three commentaries [6,10,14] can be integrated as follows. LEPS TO PAINFUL STIMULATION ARE NOT "NOCICEPTIVE RELATED" Zaslansky et al. [17] contend that LEP to painful stimula- tion is "purely cognitive processing of the P300 types and is, therefore, a reflection of the emotional processing triggered by the primary pain sensation." Such a broad statement defies the facts presented in our original Focus article and the well-balanced analysis presented by the commentary from Treede et al. [14] or the position expressed by Kakigi [10] in this issue. The confusion is not interminology but in the temporospatial sequence of activities in LEPs. Recent results [5,6,9,15] clearly dem- onstrate that the N1 (C3' IN150 or C4' IN150) mid-latency component originates from the contralateral somatosen- sory area and later exhibits bilateral activation at the homologous temporoparietal sites. This activation can be reasonably associated only to the sensory (detection, but discriminatory?) processing in LEPs. The late N2/P2 From the Center for Sensory-Motor Interaction, "Human Brain Mapping and Cortical Imaging Laboratory, and tl.aboratory for Experimental Pain Research, Aalborg University, Aalborg, Denmark; and *Centre d'Algologie-Cliniques Universitaires St Luc, Universlte Catholique de Louvain, Brussels, Belgium. Reprint request: Andrew C.N. Chen, PhD, Center for Sensory-Motor Interaction, Human Brain Mapping and Cortical Imaging Laboratory, Aalborg University, 9220 Aalborg, Denmark. © 1998 the American Pain Society 1058-9139/0704-0006$5.00/0 196 (Cz/N170 and Cz/P280) components at the vertex can be generated from the midline cingulate [4] or bilateral midtemporal hippocampus-amygdala as now sug- gested by Kakigi in his commentary [10]. The functional significance of the N2/P2 components are regarded as "nociceptive related" LEPs by us, Treede et al. [14], and others [2]. Without using the highly artificial oddball paradigm in the evoked responses to noxious stimula- tions (electrical, laser, dental, and so forth), a P3 deflec- tion sometimes can be observed following the P2 compo- nent. This is the gray area well delineated by Treede et al. [14]. The timing and topographic distribution of these different components is essential to define the plausible underlying physiological processing and the interpreta- tion of their differential functions. We just cannot lump all LEPs into either pain EP (not our term) or purely cognitive processing of the P300 type. How the N2/P2 (or even N1 to that matter) and P300 can be affected by cognitive manipulation (eg, attention, distraction, and so forth) or affective intrusion (eg, anxiety, arousal, and so forth) is itself an important issue. Bromm and Chen [1] have characterized these late components as secondary cerebral responses to the somatosensory activation of the noxious laser stimulation. However, it is inappropri- ate to say that these late components are nothing but "emotional processing" triggered by the primary pain sensation, even if it can be experimentally modulated by the anxiolytic agents. We may apply the logic that if A affects B, then B belongs only to the category of A. The late components of sensory potentials (be it somatosen- sory, auditory, or visual) are all, to some extent, ame- nable by sedatives, anxiolytics, or even narcoticanalge- sics. Specifically, we need to define the LEP activities not Pain Forum 7(4): 196-200, 1998