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

Author(s): Yu-Ting Liu, Shang-Der Chen, Yao-Chung Chuang, Fu-Zen Shaw


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.

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