Investigating the specificity of the neurologic pain signature against breathlessness and finger opposition.

ABSTRACT Brain biomarkers of pain, including pain-predictive 'signatures' based on brain activity, can provide measures of neurophysiological processes and potential targets for interventions. A central issue relates to the specificity of such measures, and understanding their current limits will both advance their development and explore potentially generalizable properties of pain to other states. Here, we utilized two datasets to test the Neurologic Pain Signature (the NPS), an established pain neuromarker. In Study 1, brain activity was measured using high-field functional magnetic resonance imaging (7T fMRI, N=40) during 5-25 seconds of experimental breathlessness (induced by inspiratory resistive loading), conditioned breathlessness anticipation and finger opposition. In Study 2, we assessed anticipation and breathlessness perception (3T, N=19) under blinded saline (placebo) and remifentanil administration. The NPS responded to breathlessness, anticipation and finger opposition, though no direct comparisons with painful events were possible. Local NPS patterns in anterior/mid-insula, S2 and dorsal anterior cingulate responded to breathlessness and finger opposition, and were reduced by remifentanil. Local NPS responses in the dorsal posterior insula did not respond to any manipulations. Therefore, significant global NPS activity alone is not specific for pain, and we offer insight into the overlap between NPS responses, breathlessness and somatomotor demand.