Neural pathways signaling cancer and inflammation: interface with stress-responsive brain regions
Challenges to the body’s host defense, such as infections, cancer, or infl ammation serve as physiological stressors. For the body to respond appropriately, the brain must be alerted to the challenge, and initiate appropriate host defense responses. To this end, viscerosensory pathways detect immune- or pathogen-related signals, and convey this information to stress response systems in the brain. The viscerosensory pathways from the body involve both neural and humoral mechanisms. Of the neural pathways, the vagus is most important for signaling the brain. In addition, spinal nerves signal pain and infl ammation in a parallel pathway. Immune and cancer related signals activate “danger pathways” originating in the caudal brainstem that drive neuroendocrine (HPA) responses to stress via their terminations in the PVN. These pathways involve primarily catecholaminergic neurons in the ventrolateral medulla and rostral nucleus of the solitary tract. A separate pathway from area postrema targets the parabrachial nucleus of the pons, which in turn infl uences other stress-sensitive forebrain regions including the paraventricular thalamus, the central amygdala and bed nucleus of the stria terminalis. The medial prefrontal, anterior cingulate, and insular cortex also contribute to the neural network that responds to different categories of stressors, such as host defense. Together these brain regions co-ordinate physiological and behavioral adjustments to homeostatic challenges.