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 travelled in the OF used as indicators of locomotor performance did not differ between treatments. Our results also reveal that in CFAtreated rats, acute administration of morphine (3 mg/kg, s.c.) abolished tactile allodynia and anxiety-like behaviors, whereas acute administration of diazepam (1 mg/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.

Persistent, comorbid pain and anxiety can be uncoupled in a mouse model

“…Similar to these previous studies in mice, our current study further confirmed that CFA-induced inflammatory pain did not alter OF and social interaction behaviors at 10 days after inflammation in both C57BL/6J and FVB/NJNju strains. In contrast, there is a large body of work on rats showing changes in anxiety and depression-like behaviors occurring in neuropathic and inflammatory pain status [25,26,[28][29][30][31]. Notably, in the present study both C57BL/6J and FVB/NJNju mice with CFA-inflammatory pain showed decreased open-arm entry in the EPM test, although there were no differences in the OF test.…”

“…However, experimental animal studies using persistent pain models found conflicting results as to whether injured mice show changes in anxiety-like behaviors [9,19,[25][26][27][28]. For example, Hasnie et al reported that nerve injury did not alter OF or EPM behavior at 1, 2 or 4 weeks after injury in C57BL/6J mice [26].…”

Pregabalin, Duloxetine, and Diazepam Selectively Modulate Acid-Induced Hyperalgesia and Anxio-Depressive Comorbidity in Rats

“…Diazepam is a classic anxiolytic, which has been demonstrated in numerous clinical studies [42] and various animal models with pain [40,43]. The present study also observed anxiolytic effect of diazepam in the acid-induced CWP model.…”

White Matter Injury and Autistic-Like Behavior Predominantly Affecting Male Rat Offspring Exposed to Group B Streptococcal Maternal Inflammation

“…The test consisted in measuring for 5 min the number and duration of active social interactions (sniffing, grooming, playing or chasing) between a pair of rats of the same sex, from different litters, with both exposed to the same experimental condition [19]. The body weights of each pair did not differ by more than 15 g. Simple passive physical contacts between the animals were not considered as social interactions, as previously described [21]. …”