Nuclei-Specific Response to Pain in the Bed Nucleus of the Stria Terminalis

Abstract

The bed nucleus of the stria terminalis (BST) is a basal forebrain cluster of several distinct nuclei. It has been proposed that the BST coordinates autonomic, neuroendocrine, and behavioral functions through the integration and organization of homeostatic responses necessary for survival. Dysfunction of the BST contributes to pathophysiological states such as addiction, anxiety and aggression. Based on anatomical and behavioral studies, the BST could be a key contributor to descending modulation of nociception as well as the physiological responses related to the affective aspect of the pain experience. The objective of the present study was to further understand the neurophysiological bases underlying the involvement of the 7 anterior nuclei of the BST in pain. Using c-Fos as an indicator of neuronal activation, the results demonstrate that acute noxious stimulation produced an increase in the number of c-Fos immunoreactive cells (c-Fos-IR) in the dorsal anteromedial (dAM) and fusiform (FU) nuclei, while non-noxious stimulation did not increase c-Fos-IR in any of the nuclei examined. Chronic neuropathic pain induced by chronic constriction injury (CCI) did not alter basal c-Fos-IR in the FU or dAM. Unlike in the naïve condition, the number of c-fos-IR cells in the FU induced by acute noxious stimulation was attenuated in animals with either CCI or sham surgery compared to naive rats. In contrast, c-Fos-IR induced by acute noxious stimulation in the dAM was not affected by CCI or sham surgery. Acute noxious stimulation in animals that received CCI exhibited increased c-Fos expression in the ventromedial (vAM) nucleus of the BST, a finding not evident in naïve or sham control groups. Finally, there was an increase in c-Fos-IR in the oval (OV) nucleus of sham-operated, but not naive or CCI rats. This study reveals for the first time that pain induces neuronal activity in the BST in a nuclei- and condition-specific way. Given the efferent projection patterns from the BST, this system may relay supraspinal information to the periphery to produce physiological responses related to the affective pain experience.