ABSTRACT
Sustained pain is a major characteristic of clinical pain disorders, but it is difficult to assess in isolation from co-occurring cognitive and emotional features in patients. In this study, we developed a functional magnetic resonance imaging signature based on whole-brain functional connectivity that tracks experimentally induced tonic pain intensity and tested its sensitivity, specificity and generalizability to clinical pain across six studies (total n = 334). The signature displayed high sensitivity and specificity to tonic pain across three independent studies of orofacial tonic pain and aversive taste. It also predicted clinical pain severity and classified patients versus controls in two independent studies of clinical low back pain. Tonic and clinical pain showed similar network-level representations, particularly in somatomotor, frontoparietal and dorsal attention networks. These patterns were distinct from representations of experimental phasic pain. This study identified a brain biomarker for sustained pain with high potential for clinical translation.
Subject(s)
Biomarkers/analysis , Functional Neuroimaging/methods , Pain Measurement/methods , Adolescent , Adult , Aversive Agents/toxicity , Capsaicin/toxicity , Connectome/methods , Connectome/statistics & numerical data , Facial Pain/physiopathology , Female , Functional Neuroimaging/statistics & numerical data , Humans , Low Back Pain/physiopathology , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/statistics & numerical data , Male , Models, Neurological , Nerve Net/physiopathology , Pain/physiopathology , Pain Measurement/statistics & numerical data , Predictive Value of Tests , Sensitivity and Specificity , Taste/drug effects , Taste/physiology , Young AdultABSTRACT
Reduced food intake is common to many pathological conditions, such as infection and toxin exposure. However, cortical circuits that mediate feeding responses to these threats are less investigated. The anterior insular cortex (aIC) is a core region that integrates interoceptive states and emotional awareness and consequently guides behavioral responses. Here, we demonstrate that the right-side aIC CamKII+ (aICCamKII) neurons in mice are activated by aversive visceral signals. Hyperactivation of the right-side aICCamKII neurons attenuates food consumption, while inhibition of these neurons increases feeding and reverses aversive stimuli-induced anorexia and weight loss. Similar manipulation at the left-side aIC does not cause significant behavioral changes. Furthermore, virus tracing reveals that aICCamKII neurons project directly to the vGluT2+ neurons in the lateral hypothalamus (LH), and the right-side aICCamKII-to-LH pathway mediates feeding suppression. Our studies uncover a circuit from the cortex to the hypothalamus that senses aversive visceral signals and controls feeding behavior.
