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J Neurotrauma. 2018 Jan 15;35(2):297-307. doi: 10.1089/neu.2017.5061. Epub 2017 Nov 20.

Repeated Exposure to Experimental Pain Differentiates Combat Traumatic Brain Injury with and without Post-Traumatic Stress Disorder.

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1 Veterans Affairs San Francisco Healthcare System , San Francisco, California.
2 University of California San Francisco , San Francisco, California.
3 Veterans Affairs San Diego Healthcare System , San Diego, California.
4 University of California , San Diego, La Jolla, California.


Mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are highly comorbid conditions that often co-occur with chronic pain. We have shown that women with PTSD subsequent to intimate partner violence show attenuated brain response to repeated experimental pain that was related to symptoms of avoidance. The aim of this study was to extend our past findings to males with combat trauma and to examine brain response to experimental pain in men with and without PTSD who sustained mTBI during combat. Seventy male veterans performed an experimental pain paradigm during functional magnetic resonance imaging fMRI. Of the 70 total subjects, 46 self-reported a history of mTBI during combat (46 of 70). Of those with mTBI, 26 also met criteria for PTSD (26 of 46). As in our previous study, we examined change in brain activity to repeated heat pain with linear mixed-effects modeling for group by administration interaction effects. We observed a significant group by administration interaction to repeated heat pain within insular, frontal, and parietal cortices, such that the control group showed increased activation over time, whereas mTBI groups (mTBI-only, mTBI + PTSD) showed decreased activation within bilateral anterior insulas (AIs) between administrations. Importantly, change in the right AI response was inversely correlated with avoidance symptoms, but only in those with comorbid mTBI + PTSD. Further, in the comorbid group, greater AI attenuation was associated with decreased connectivity with anterior cingulate (ACC). The current study provides further evidence that repeated exposure to brief painful stimuli results in attenuation of insula activation over time in traumatized individuals. Further, in PTSD, AI shows greatest attenuation in those with the highest level of avoidance-a finding that was replicated across diverse samples. Thus, this mechanism may be a generalized mechanism of maladaptive response to experimental pain in those with significant trauma.


avoidance; emotion; imaging; insula; salience


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