Quantifying pain currently relies upon subjective self-report. Alongside the inherent variability embedded within these metrics, added complications include the influence of ambiguous or prolonged noxious inputs, or in situations when communication may be compromised. As such, there is continued interest in the development of brain biomarkers of pain, such as in the form of neural signatures of brain activity. However, issues pertaining to pain-related specificity remain, and by understanding the current limits of these signatures we can both progress their development and investigate the potentially generalizable properties of pain to other salient and/or somatomotor tasks. Here, we utilized two independent datasets to test one of the established Neural Pain Signatures (the NPS (Wager et al. 2013)). In Study 1, brain activity was measured using functional magnetic resonance imaging (fMRI) in 40 healthy subjects during experimentally induced breathlessness, conditioned anticipation of breathlessness and a simple finger opposition task. In Study 2, brain activity was again measured during anticipation and breathlessness in 19 healthy subjects, as well as a modulation with the opioid remifentanil. We were able to identify significant NPS-related brain activity during anticipation and perception of breathlessness, as well as during finger opposition using the global NPS. Furthermore, localised NPS responses were found in early somatomotor regions, bilateral insula and dorsal anterior cingulate for breathlessness and finger opposition. In contrast, no conditions were able to activate the local signature in the dorsal posterior insula - thought to be critical for pain perception. These results provide properties of the present boundaries of the NPS, and offer insight into the overlap between breathlessness and somatomotor conditions with pain.
