Study of emotional and cognitive impairments in mononeuropathic rats: effect of duloxetine and gabapentin.
Chronic pain is a multidimensional experience that not only includes changes in nociception, but also impairments in emotion and cognitive functions. These last 2 components are not often taken into account in preclinical research. We investigated emotional and cognitive impairments in a model of neuropathic pain in rats induced by chronic constriction injury (CCI) of the sciatic nerve. Nociceptive response, anxiety and depressive-like behaviours as well as cognitive capacities were analysed, and the effect of per os administration of duloxetine and gabapentin was studied. In the electronic von Frey test, CCI rats exhibited mechanical hypersensitivity which can be influenced by duloxetine (3-30 mg/kg) and gabapentin (10-30 mg/kg). Cognitive impairments were found in the social but not in the spatial (Y-maze) recognition memory tests. Duloxetine and gabapentin dose-dependently (3-30 mg/kg) restored social recognition memory impairment. Anxiety-like behaviour was only observed in the open-field test (decrease in the time spent in the inner zone) but not in the elevated plus maze or in the social interactions tests in CCI animals. In this test, impairment in locomotor activity (decrease of the total number of crossing) was also observed. Duloxetine and gabapentin (10mg/kg) were effective to increase the time spent in the inner zone as well as locomotor activity. No difference was observed in depressive-like behaviour (saccharin preference test) between sham-operated and CCI rats. These data suggest that cognitive rather than emotional impairments seem to be present in neuropathic CCI rats and can be reversed by duloxetine and gabapentin.
Clermont Université, Université d'Auvergne, NEURO-DOL, BP 10448, F-63000, CLERMONT-FERRAND Inserm, U1107, F-63001 Clermont-Ferrand, France.
Stéphanie
S
Grégoire
Vincent
V
Michaud
Eric
E
Chapuy
Alain
A
Eschalier
Denis
D
Ardid
D000342:Affective Symptoms / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068736:Duloxetine Hydrochloride; D004644:Emotions / Q000187:drug effects; D000077206:Gabapentin; D008297:Male; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000494:pharmacology*; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; D000928:Antidepressive Agents; D003509:Cyclohexanecarboxylic Acids; D013876:Thiophenes; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000068736:Duloxetine Hydrochloride