Central nucleus of the amygdala in descending control of pain-related behavior

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http://urn.fi/URN:ISBN:978-951-51-1383-2
Title: Central nucleus of the amygdala in descending control of pain-related behavior
Author: Bourbia, Nora
Contributor: University of Helsinki, Faculty of Medicine, Institute of Biomedicine, Physiology
Thesis level: Doctoral dissertation (article-based)
Abstract: The central nucleus of amygdala (CeA) is known to be involved in pain and nociception, but the mechanisms or its role in descending control of pain-related behavior is poorly understood. The aim of this study was to investigate the involvement of the neuropeptide corticotropin-releasing factor (CRF) and the glutamatergic system of the CeA in pain and nociception in healthy control animals and in an animal model of chronic neuropathic pain induced by spared-nerve injury (SNI). Two aspects of pain were studied: emotional-like pain behavior was assessed by using the aversive place-avoidance paradigm and sensory-discriminative was assessed by determining the mechanical limb-withdrawal threshold and the thermal (heat) limb-withdrawal latency. Moreover, the aims were to determine whether medullospinal serotoninergic pathways and the midbrain periaqueductal grey (PAG), respectively, were involved in relaying pain-modulation induced by the CeA in SNI and healthy control animals. Additionally, hemisphere of the CeA and submodality of pain stimulus were among studied parameters. Surgical procedures and electrophysiological recordings were performed under general anesthesia. The studies on the role of the CeA in the emotional-like aspect of pain in SNI rats revealed that activation and blocking of the group I metabotropic glutamate receptors (mGluRs) facilitates and inhibits, respectively, the aversive aspect of pain. Furthermore, increase of endogenous CRF as well as blocking glutamatergic N-methyl-D-aspartate (NMDA) receptors in the CeA reduced the aversive aspect of neuropathic pain. The studies on the sensory-discriminative aspect of pain revealed that an increase of endogenous CRF in the CeA is pronociceptive in both control and SNI rats. CeA injection of a high dose of glutamate had a mechanical antinociceptive effect that was mediated by NMDA receptors in healthy but not SNI rats. A low dose of glutamate had a pronociceptive effect mediated by NMDA receptors in SNI rats. Furthermore, tonic descending pronociception induced by NMDA receptors and the mGluR1 in the CeA contributes to the maintenance of neuropathic hypersensitivity. The investigation on the role of serotonergic neurons of the rostroventromedial medulla (RVM) in modulation of spinal nociception by amygdaloid glutamate in SNI rats indicated that the RVM is a relay for both descending pro- and antinociceptive effects from the CeA. The investigation on the role of the PAG in the descending control of nociception induced by glutamate in the CeA of healthy rats indicated that the PAG is a relay in the descending control of nociception induced by amygdaloid glutamate. Furthermore, the right-hemispheric lateralization of the pronociceptive effect by amygdaloid CRF in controls was lost in SNI rats. However, descending antinociception induced by the glutamatergic system of the CeA showed no hemispheric lateralization in healthy controls; a high dose of glutamate in both the left and right CeA induced equal attenuations of mechanical and thermal nociception, which effects were, respectively, NMDA-dependent and NDMA-independent.-
URI: URN:ISBN:978-951-51-1383-2
http://hdl.handle.net/10138/155702
Date: 2015-08-11
Subject: neuroscience
Rights: This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.


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