Extracranial Hemodynamic Responses to a Noxious Cold Pressor Task Differ Between Persistent Post-Traumatic Headache and Healthy Controls

<b>Background/Objectives:</b> Headache after a traumatic brain injury (TBI) is one of the most common post-concussive symptoms and is associated with altered pain processing and elevated disability levels. Understanding physiologic correlates of nociception in individuals with persistent post-traumatic headache (pPTH) may help identify novel treatment targets for pain-related disability. The objective of this case-control study was to compare extra- and intracranial hemodynamic responses to a noxious cold pressor task (CPT) between individuals with pPTH and healthy controls (HC) using functional near-infrared spectroscopy (fNIRS). <b>Methods:</b> Ten individuals with pPTH were compared to ten HC with no history of TBI, persistent headache, or chronic pain. fNIRS optodes over the medial prefrontal cortex (PFC) measured extra- and intracranial peak-to-peak hemodynamic responses during tepid- (control) and cold-water (CPT) hand immersion. Evoked pain responses during the CPT were assessed with numeric pain ratings. Linear mixed effects modeling assessed the role of group and evoked pain on hemodynamic responses. <b>Results:</b> pPTH group membership (<i>p</i> = 0.031) predicted greater extracranial hemodynamic responses to the CPT, whereas intracranial PFC responses did not differ between groups. Regardless of group membership, greater increases in pain intensity during the CPT were associated with increased hemodynamic responses for the dorsomedial PFC (<i>p</i> = 0.031). <b>Conclusions:</b> Compared to controls, individuals with pPTH responded to a noxious cold stimulus with elevated systemic hemodynamic responses regulated by the autonomic nervous system. Irrespective of group, hemodynamic responses within the dmPFC were associated with evoked pain responses to the CPT and may provide a useful biomarker for individual variations in cortical pain processing for healthy and clinical populations.