7, whereas there is no correlation between VAS score and BOLD in HC, and between age and BOLD signal in UWS patients. It is known that the subjective threshold of pain experience increases with age (Gibson and Helme 2001). Unresponsive wakefulness state The inability to experience pain (or any other subjective feeling) is a central part of the MAPK inhibitor definition of the UWS. Despite

this definition, not only patients’ relatives but also many health professionals believe that UWS patients can perceive pain. Demertzi et al. (2009) asked 2059 medical Inhibitors,research,lifescience,medical and paramedical professionals in Europe about their beliefs concerning the vegetative or minimally conscious states. Of the paramedical caregivers and medical doctors, 68% and 56%, respectively, believed that a UWS patient can feel pain. In several studies using PET, pain-related activations in UWS patients

were observed exclusively in the primary sensory part of the pain matrix, indicating that higher order processing of noxious stimuli was lacking (e.g. Boly et al. 2005, 2008). In a smaller study of Kassubek et al. Inhibitors,research,lifescience,medical (2003), in contrast, activations of the sensory-discriminative and affective parts of the pain network were obtained in each of the examined seven UWS patients. The present data indicate clear individual differences in pain responsiveness of UWS patients. While no pain-related activation was found in 14 patients, the Inhibitors,research,lifescience,medical others did respond to noxious stimuli. Fifteen UWS patients showed activation in the sensory-discriminative part of the pain matrix and nine patients (30%) showed even affective pain-related responses. In 15 patients, higher order pain control Inhibitors,research,lifescience,medical areas (ACC, anterior insula, S2) were also involved. Moreover, about one-third of the UWS patients had pain-related responses in both, the sensory and affective parts of the pain matrix, thus replicating the PET findings of Kassubek et al. (2003) at least for a subgroup of UWS patients. In our study, a trend to more frequent Inhibitors,research,lifescience,medical activations of the pain matrix in (sub)acute UWS patients as compared with chronic UWS patients was observed.

The somatosensory cortex receives noxious input from the thalamus and contains neurons that code spatial, temporal, and intensity of noxious somatosensory stimuli (Derbyshire 2000; Price 2002), characteristics that constitute the sensory-discriminative dimension of pain processing. The ACC and the insular cortex are considered to be brain areas of the classical limbic system and are involved in the processing of the either affective-motivational dimension of pain (Price 2002). The insula has been implicated in pain sensation and comprise the only cortical areas in which direct electrical stimulation produces a perception of pain (Ostrowsky et al. 2002; Frot and Mauguiere 2003). Especially, the anterior insula is related to interoceptive awareness (Craig 2008), emotional salience, awareness of subjective feeling, and bodily arousal states (Craig 2002).