Stressinduced Visceral Hyperalgesia

The body could be subjected to a variety of stressors that have been commonly subdivided into two categories: exteroceptive (psychological or neurogenic) and interoceptive (physical or systemic). Exteroceptive stressors become stressful only after being processed in the context of previous experiences and are, therefore, limbic sensitive. Brain circuits mediating the endocrine and autonomic response to exteroceptive stressors encompass the limbic-sensitive neural network, namely, the cortex (lateral, medial prefrontal, ventromedial, perigenual, and infra-genual cingulate), bed nucleus of the stria terminalis, lateral septum, hippocampus, amygdala, hypothalamus (mainly paraventricular nucleus, PVN), and periaqueductal gray (PAG) (Fig. 1A) (17-20). The impacts of exteroceptive stressors on cortical structures are conveyed to these forebrain and hindbrain nuclei which themselves have projections to pontomedullary nuclei (Fig. 1A) (21,22). With regard to interoceptive or limbic-insensitive stressors that represent a threat to the homeostasis (such as immune stress), the cognitive processing is bypassed and brainstem/pontine nuclei such as the lateral parabrachial nucleus, nucleus tractus solitarius, brainstem/pontine catecholaminergic neurons in the ventrolateral medulla and the locus

Figure 1 Schematic drawing of the neural circuits by which exteroceptive (A) and interoceptive (B) stressors induce endocrine and autonomic responses that impact on peripheral organs. Abbreviations: BST, bed nucleus of the stria terminalis; LC, locus coeruleus; LS, lateral septum; PA, pituitary adrenal axis; PVN, paraventricular nucleus.

Figure 1 Schematic drawing of the neural circuits by which exteroceptive (A) and interoceptive (B) stressors induce endocrine and autonomic responses that impact on peripheral organs. Abbreviations: BST, bed nucleus of the stria terminalis; LC, locus coeruleus; LS, lateral septum; PA, pituitary adrenal axis; PVN, paraventricular nucleus.

coeruleus (LC), respectively, receive sensory visceral input (Fig. 2) (17-20). In both exteroceptive and interoceptive types of stressors, the PVN serve as the principal gateway conveying actions on the pituitary-adrenal axis (endocrine) and autonomic nervous system which are the two main effector arms of the stress response (Fig. 1) (23-25).

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