Altered emotionality leads to increased pain tolerance in amyloid beta (Abeta1-40) peptide-treated mice.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the decline in cognitive functions, but it is also related to emotional disturbances. Since pain experience results from a complex integration of sensory, cognitive and affective processes, it is not surprising that AD patients display a distinct pattern of pain responsivity. We evaluated whether mice treated with amyloid beta (Abeta) peptide-thought to be critical in the pathogenesis of AD-exhibit altered pain responses and its relation to altered emotionality. Mice received a single i.c.v. injection of vehicle (PBS) or Abeta fragment (1-40) (400pmol/mice) and after 30 days, they were evaluated in tests of pain (hotplate, footshock-sensitivity), learning/memory (water-maze), emotionality (elevated plus-maze, forced swim) and locomotion (open-field). Abeta(1-40)-treated mice presented similar latencies to the control group in the hotplate test and similar nociceptive flinch threshold in the footshock-sensitivity test. However, they presented an increased jump threshold in footshock-sensitivity, suggesting increased pain tolerance. Altered emotionality was observed in the elevated plus-maze (EPM) and forced-swim tests (FST), suggesting anxiogenic-like and depressive-like states, respectively. A multifactorial principal component analysis (PCA) revealed that jump threshold of the footshock-sensitivity test falls within 'Emotionality' and 'Pain', showing moderate correlation with each one of the components of behavior. Acute treatment with the antidepressant desipramine (10mg/kg, i.p.) reduced the jump threshold (i.e. pain tolerance) and time of immobility in FST (i.e. depressive-like state). Flinch threshold (i.e. pain sensitivity), locomotion and anxiety were not altered with desipramine treatment. These results suggest that Abeta(1-40) peptide increases pain tolerance, but not pain sensitivity in mice, which seems to be linked to alterations in cognitive/emotional components of pain processing.

• Authors: Fabrício A Pamplona, Pablo Pandolfo, Filipe S Duarte, Reinaldo N Takahashi, Rui D S Prediger
• Journal: Behavioural brain research (Behav Brain Res) Vol. 212 Issue 1 Pg. 96-102 (Sep 01 2010) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 20363258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Enzyme Inhibitors
• Peptide Fragments
• amyloid beta-protein (1-40)
• Desipramine

Topics

• Amyloid beta-Peptides (pharmacology)
• Animals
• Behavior, Animal (drug effects)
• Cognition (drug effects)
• Desipramine (pharmacology)
• Disease Models, Animal
• Drug Interactions
• Electroshock (adverse effects)
• Emotions (drug effects)
• Enzyme Inhibitors (pharmacology)
• Exploratory Behavior (drug effects)
• Humans
• Immobility Response, Tonic (drug effects)
• Male
• Maze Learning (drug effects)
• Mice
• Motor Activity (drug effects)
• Pain (drug therapy, etiology)
• Pain Measurement (drug effects, methods)
• Pain Threshold (drug effects)
• Peptide Fragments (pharmacology)