Altered emotionality leads to increased pain tolerance in amyloid beta (Abeta1-40) peptide-treated mice.
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.
Pamplona
Fabrício A
FA
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC 88049-900, Brazil. fabriciopamplona@gmail.com
Pandolfo
Pablo
P
Duarte
Filipe S
FS
Takahashi
Reinaldo N
RN
Prediger
Rui D S
RD
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004597:Electroshock / Q000009:adverse effects; D004644:Emotions / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006801:Humans; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D003891:Desipramine