title: Neuropathic pain is associated with depressive behaviour and induces neuroplasticity in the amygdala of the rat.
abstract: Chronic pain is associated with the development of affective disorders but the underlying mechanisms are not fully understood. Changes in brain centres implicated in both emotional and pain processing are likely to be critical in the interplay of pain control and affective emotional behaviour. In the present study, we assessed emotional behaviour and performed a structural analysis of the amygdala (AMY) in neuropathic rats after two months of hyperalgesia and allodynia, induced by the spared nerve injury model (SNI). When compared with Sham-controls, SNI animals displayed signs of depressive-like behaviour. In addition, we found an increased amygdalar volume in SNI rats. No alterations were found in the dendritic arborizations of AMY neurons but, surprisingly, the amygdalar hypertrophy was associated with an increased cell proliferation [bromodeoxyuridine (BrdU)-positive cells] in the central (CeA) and basolateral (BLA) amygdaloid nuclei. The phenotypic analysis of the newly-acquired cells revealed that they co-label for neuronal markers (BrdU+NeuN and BrdU+Calbindin), but not for differentiated glial cells (BrdU+glial fibrillary acidic protein). We demonstrate that neuropathic pain promotes generation of new neurons in the AMY. Given the established role of the AMY in emotional behaviour, we propose that these neuroplastic changes might contribute for the development of depressive-like symptoms that are usually present in prolonged pain syndromes in humans.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Leonor
authors.initials: L
authors.lastname: Gonçalves
authors.forename: Rui
authors.initials: R
authors.lastname: Silva
authors.forename: Filipa
authors.initials: F
authors.lastname: Pinto-Ribeiro
authors.forename: José M
authors.initials: JM
authors.lastname: Pêgo
authors.forename: João M
authors.initials: JM
authors.lastname: Bessa
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.forename: Armando
authors.initials: A
authors.lastname: Almeida
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D064026:Calbindins; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002908:Chronic Disease / Q000523:psychology; D004268:DNA-Binding Proteins; D003866:Depressive Disorder / Q000209:etiology / Q000503:physiopathology*; D006930:Hyperalgesia / Q000150:complications / Q000503:physiopathology / Q000523:psychology; D006984:Hypertrophy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology; D009687:Nuclear Proteins / Q000378:metabolism; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000150:complications / Q000503:physiopathology / Q000523:psychology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D064026:Calbindins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D064030:S100 Calcium Binding Protein G