Objective:Patients with chronic widespread pain (CWP) syndrome often have comorbid with depression/ anxiety symptoms and unsatisfied. Effects of pregabalin, duloxetine and diazepam in the well-established acid-induced CWP model remain unclear. This study aimed to assess these medicines on mechanical hyperalgesia and psychiatric comorbidity in this CWP model.
Methods:The CWP model was elicited by repeated injections of acidic solution into unilateral gastrocnemius muscle of a rat. Each medicine was administered orally via gavage twice per day for >2 weeks. Paw withdrawal threshold (PWT) was evaluated by von Frey filaments. Anxiety-like behavior was assessed by an elevated plus maze. Despair mood and anhedonia of depression-like behavior were evaluated using the forced swimming and sucrose preference tests, respectively.
Results:Rats receiving acid injections displayed bilateral hyperalgesia and anxio-depressive comorbidity. Pregabalin significantly increased PWTs and ameliorated anxiety-like and anhedonic behaviours. Duloxetine significantly increased PWTs and ameliorated depressionlike but not anxiety-like behaviour. Diazepam did not alter PWTs but remedied anxiety-like and anhedonic behaviours. Pregabalin, duloxetine, and diazepam revealed different effects on hyperalgesia and anxio-depressive comorbidity in the acid-induced CWP model.
Conclusion:Our results strengthen the acid-induced pain model as humans with CWP on additional evidences of face and predictive validities. This study provides information of these medicines on selective treatment of pain and psychiatric comorbidity.
Keywords:Muscle pain, Fibromyalgia, Pregabalin, Duloxetine, Diazepam, Anxiety, Depression Neuropsychiatry (London) (2017) 7(6)
850Research Fu-Zen Shaw via gavage. We hypothesized that these drugs would selectively modulate hyperalgesia and comorbidity of anxiety-and depression-like behaviors in the acid-induced CWP animal model. The results of this study provided predictive validity between acid-induced muscle pain in CWP animal model and patients with CWP syndromes and also extended our understanding of these medicines on CWP syndromes and psychiatric comorbidity.
MethodsMale Sprague-Dawley rats (8-9 weeks old) were kept in a sound-attenuated room under a 12/12-h light/dark cycle (lights on at 06:00-18:00) with food and water provided ad libitum. The rats were randomly assigned into a group receiving the vehicle (pH 7.2) or acidic saline (pH 4.0) at a ratio of 1:1