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

Abstract

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

The Fibromyalgia Pain Experience: A Scoping Review of the Preclinical Evidence for Replication and Treatment of the Affective and Cognitive Pain Dimensions

“…Investigations of the acidic saline model's ability to induce negative emotionality associated with FMS-like pain yielded mixed results, with negative affect being inconsistent across various behavioral assays. Studies were identified with contrasting results within measures of EPM [93][94][95][96][97], OFT [65,93,97,98], sucrose measures [93,97], and FST [65,93,97,98]. Differences in avoidance behavior were not produced by the administration of acidic saline [65,99].…”

“…Differences in avoidance behavior were not produced by the administration of acidic saline [65,99]. Antidepressants: [97] Benzodiazepines: [97] Anticonvulsants: [65,93,94,97,99] Alternative Devices: [98] Organics: [93] Other: [93][94][95][96][97]99] Non-significant: [96] [99] -Organics: [94] Inconclusive:…”

“…While manifestations of negative emotionality varied significantly across studies, the efficacy of various treatment mechanisms for the alleviation of negative affect was investigated in the case where negative affect was able to be effectively identified. Diazepam, pregabalin, and duloxetine were inconsistent in their ability to relieve negative affect within animals, dependent on the behavioral paradigm that was being investigated [93,94]. Mirogabalin, however, did show promise in alleviating the negative affect observed in animals in measures of EPM and OFT [95].…”