title: Increased anxiety-like behaviors in rats experiencing chronic inflammatory pain.
abstract: For many patients, chronic pain is often accompanied, and sometimes amplified, by co-morbidities such as anxiety and depression. Although it represents important challenges, the establishment of appropriate preclinical behavioral models contributes to drug development for treating chronic inflammatory pain and associated psychopathologies. In this study, we investigated whether rats experiencing persistent inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) developed anxiety-like behaviors, and whether clinically used analgesic and anxiolytic drugs were able to reverse CFA-induced anxiety-related phenotypes. These behaviors were evaluated over 28 days in both CFA- and saline-treated groups with a variety of behavioral tests. CFA-induced mechanical allodynia resulted in increased anxiety-like behaviors as evidenced by: (1) a significant decrease in percentage of time spent and number of entries in open arms of the elevated-plus maze (EPM), (2) a decrease in number of central squares visited in the open field (OF), and (3) a reduction in active social interactions in the social interaction test (SI). The number of entries in closed arms in the EPM and the distance traveled in the OF used as indicators of locomotor performance did not differ between treatments. Our results also reveal that in CFA-treated rats, acute administration of morphine (3mg/kg, s.c.) abolished tactile allodynia and anxiety-like behaviors, whereas acute administration of diazepam (1mg/kg, s.c) solely reversed anxiety-like behaviors. Therefore, pharmacological treatment of anxiety-like behaviors induced by chronic inflammatory pain can be objectively evaluated using multiple behavioral tests. Such a model could help identify/validate alternative potential targets that influence pain and cognitive dimensions of anxiety.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Institut de pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Alexandre J
authors.initials: AJ
authors.lastname: Parent
authors.forename: Nicolas
authors.initials: N
authors.lastname: Beaudet
authors.forename: Hélène
authors.initials: H
authors.lastname: Beaudry
authors.forename: Jenny
authors.initials: J
authors.lastname: Bergeron
authors.forename: Patrick
authors.initials: P
authors.lastname: Bérubé
authors.forename: Guy
authors.initials: G
authors.lastname: Drolet
authors.forename: Philippe
authors.initials: P
authors.lastname: Sarret
authors.forename: Louis
authors.initials: L
authors.lastname: Gendron
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology*; D002908:Chronic Disease; D003623:Dark Adaptation / Q000187:drug effects; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005620:Freund's Adjuvant / Q000009:adverse effects; D007839:Functional Laterality; D006930:Hyperalgesia / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D007398:Interpersonal Relations; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D009161:Mycobacterium / Q000737:chemistry; D009294:Narcotics / Q000627:therapeutic use; D010146:Pain / Q000150:complications* / Q000209:etiology*; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D009294:Narcotics; D009020:Morphine; D005620:Freund's Adjuvant; D003975:Diazepam