Pain subserves different functions. Acute pain from the intact body alerts the victim to immediately react and withdraw from the bodily threat, ideally before an injury happens. However, during manifest injury and tissue inflammation, withdrawal and flight are no longer adaptive. Instead, sparing the affected body part to promote healing requires heightened awareness and avoidance behaviour over longer periods of time. Quality and time scales of behavioural adaptations are therefore substantially different between pain during normal compared to abnormal tissue states. Given these functional differences we postulated that the two phenomena also recruit different forebrain systems. We used positron emission tomography (PET) and subtracted scans obtained during painful heating of normal skin from scans during equally intense but normally non-painful heating of capsaicin-treated skin. This comparison reveals the specific activation of a medial thalamic pathway to limbic forebrain structures such as anterior insula, perigenual anterior cingulate, ventral striatum, and prefrontal cortex during pain originating in the chemically sensitised skin. It is possible that the unique forebrain recruitment by pain under a patho-physiological tissue status is caused by a significantly greater facilitation of the multi-synaptic projections from the spino-parabrachial tract of the superficial dorsal horn to the medial thalamus compared to deeper and direct lateral thalamic projections from the spino-thalamic tract.