Under physiological conditions, momentary pain serves vital protective functions. Ongoing pain in chronic pain states, on the other hand, is a pathological condition that causes widespread suffering and whose treatment remains unsatisfactory. The brain mechanisms of ongoing pain are largely unknown. In this study, we applied tonic painful heat stimuli of varying degree to healthy human subjects, obtained continuous pain ratings, and recorded electroencephalograms to relate ongoing pain to brain activity. Our results reveal that the subjective perception of tonic pain is selectively encoded by gamma oscillations in the medial prefrontal cortex. We further observed that the encoding of subjective pain intensity experienced by the participants differs fundamentally from that of objective stimulus intensity and from that of brief pain stimuli. These observations point to a role for gamma oscillations in the medial prefrontal cortex in ongoing, tonic pain and thereby extend current concepts of the brain mechanisms of pain to the clinically relevant state of ongoing pain. Furthermore, our approach might help to identify a brain marker of ongoing pain, which may prove useful for the diagnosis and therapy of chronic pain.

Noxious stimuli induce physiological processes which commonly translate into pain. However, under certain conditions, pain intensity can substantially dissociate from stimulus intensity, e.g. during longer-lasting pain in chronic pain syndromes. How stimulus intensity and pain intensity are differentially represented in the human brain is, however, not yet fully understood. We therefore used electroencephalography (EEG) to investigate the cerebral representation of noxious stimulus intensity and pain intensity during 10 min of painful heat stimulation in 39 healthy human participants. Time courses of objective stimulus intensity and subjective pain ratings indicated a dissociation of both measures. EEG data showed that stimulus intensity was encoded by decreases of neuronal oscillations at alpha and beta frequencies in sensorimotor areas. In contrast, pain intensity was encoded by gamma oscillations in the medial prefrontal cortex. Contrasting right versus left hand stimulation revealed that the encoding of stimulus intensity in contralateral sensorimotor areas depended on the stimulation side. In contrast, a conjunction analysis of right and left hand stimulation revealed that the encoding of pain in the medial prefrontal cortex was independent of the side of stimulation. Thus, the translation of noxious stimulus intensity into pain is associated with a change from a spatially specific representation of stimulus intensity by alpha and beta oscillations in sensorimotor areas to a spatially independent representation of pain by gamma oscillations in brain areas related to cognitive and affective-motivational processes. These findings extend the understanding of the brain mechanisms of nociception and pain and their dissociations during longer-lasting pain as a key symptom of chronic pain syndromes.

The perception of pain is characterized by its tremendous intra- and interindividual variability. Different individuals perceive the very same painful event largely differently. Here, we aimed to predict the individual pain sensitivity from brain activity. We repeatedly applied identical painful stimuli to healthy human subjects and recorded brain activity by using electroencephalography (EEG). We applied a multivariate pattern analysis to the time-frequency transformed single-trial EEG responses. Our results show that a classifier trained on a group of healthy individuals can predict another individual's pain sensitivity with an accuracy of 83%. Classification accuracy depended on pain-evoked responses at about 8 Hz and pain-induced gamma oscillations at about 80 Hz. These results reveal that the temporal-spectral pattern of pain-related neuronal responses provides valuable information about the perception of pain. Beyond, our approach may help to establish an objective neuronal marker of pain sensitivity which can potentially be recorded from a single EEG electrode.

Chronic pain is a major health care issue characterized by ongoing pain and a variety of sensory, cognitive, and affective abnormalities. The neural basis of chronic pain is still not completely understood. Previous work has implicated prefrontal brain areas in chronic pain. Furthermore, prefrontal neuronal oscillations at gamma frequencies (60-90 Hz) have been shown to reflect the perceived intensity of longer lasting experimental pain in healthy human participants. In contrast, noxious stimulus intensity has been related to alpha (8-13 Hz) and beta (14-29 Hz) oscillations in sensorimotor areas. However, it is not fully understood how the intensity of ongoing pain as the key symptom of chronic pain is represented in the human brain. Here, we asked 31 chronic back pain patients to continuously rate their ongoing pain while simultaneously recording electroencephalography (EEG). Time-frequency analyses revealed a positive association between ongoing pain intensity and prefrontal beta and gamma oscillations. No association was found between pain and alpha or beta oscillations in sensorimotor areas. These findings indicate that ongoing pain as the key symptom of chronic pain is reflected by neuronal oscillations implicated in the subjective perception of longer lasting pain rather than by neuronal oscillations related to the processing of objective nociceptive input. The findings, thus, support a dissociation of pain intensity from nociceptive processing in chronic back pain patients. Furthermore, although possible confounds by muscle activity have to be taken into account, they might be useful for defining a neurophysiological marker of ongoing pain in the human brain.

Perception is not a simple reflection of sensory information but varies within and between individuals. This applies particularly to the perception of pain, which, in the brain, is associated with neuronal responses at different frequencies. Here, we show how these different neuronal responses subserve interindividual and intraindividual variations in the perception of identical painful stimuli. A time-frequency analysis of single trial electroencephalographic data indicates that pain-related responses in the theta frequency range but not at higher gamma frequencies code for interindividual variations in the perception of pain. In contrast, both pain-related theta and gamma responses provide different and complementary information on intraindividual variations in the pain experience. We conclude that theta responses reflect rather constant physiological and psychological traits of the individual, whereas gamma responses relate to short-term modulations of the individual's state. These findings reveal how neuronal responses at different frequencies differentially contribute to the translation of sensory information into a subjective percept.