title: Asymmetric c-fos expression in the ventral orbital cortex is associated with impaired reversal learning in a right-sided neuropathy.
abstract: BACKGROUND
  Recently we showed that unilateral peripheral neuropathic lesions impacted differentially on rat's emotional/cognitive behavior depending on its left/right location; importantly, this observation recapitulates clinical reports. The prefrontal cortex (PFC), a brain region morphofunctionally affected in chronic pain conditions, is involved in the modulation of both emotion and executive function and displays functional lateralization. To test whether the PFC is involved in the lateralization bias associated with left/right pain, c-fos expression in medial and orbital areas was analyzed in rats with an unilateral spared nerve injury neuropathy installed in the left or in the right side after performing an attentional set-shifting, a strongly PFC-dependent task.
  
  
  RESULTS
  SNI-R animals required more trials to successfully terminate the reversal steps of the attentional set-shifting task. A generalized increase of c-fos density in medial and orbital PFC (mPFC/OFC), irrespectively of the hemisphere, was observed in both SNI-L and SNI-R. However, individual laterality indexes revealed that contrary to controls and SNI-L, SNI-R animals presented a leftward shift in c-fos density in the ventral OFC (VO). None of these effects were observed in the neighboring primary motor area.
  
  
  CONCLUSIONS
  Our results demonstrate that chronic neuropathic pain is associated with a bilateral mPFC and OFC hyperactivation. We hypothesize that the impaired performance of SNI-R animals is associated with a left/right activity inversion in the VO, whose functional integrity is critical for reversal learning.
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal. hugoalmeida@ecsaude.uminho.pt.
authors: Hugo
authors: H
authors: Leite-Almeida
authors: Marco Rafael
authors: MR
authors: Guimarães
authors: João José
authors: JJ
authors: Cerqueira
authors: Nuno
authors: N
authors: Ribeiro-Costa
authors: Helena
authors: H
authors: Anjos-Martins
authors: Nuno
authors: N
authors: Sousa
authors: Armando
authors: A
authors: Almeida
mesh_terms: D000818:Animals; D001288:Attention / Q000502:physiology; D002452:Cell Count; D004192:Discrimination, Psychological; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology*; D007859:Learning Disabilities / Q000209:etiology*; D008297:Male; D009437:Neuralgia / Q000150:complications* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold; D010812:Physical Stimulation; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012193:Reversal Learning / Q000502:physiology*; D018709:Statistics, Nonparametric
chemical_list: D016760:Proto-Oncogene Proteins c-fos