Kinin B1 receptor is involved in mechanical nociception in a fibromyalgia-like model in mice

Abstract

Fibromyalgia-like models in mice induced by reserpine have opened a new avenue to understanding the molecular mechanisms behind this complex and incapacitating pain syndrome. The kinin B1 receptor (B1R) contributes to mechanical allodynia and acute coping behavior in mice with inflammatory and immunological disorders. This study has replicated previous data where amine depletion induced by reserpine significantly decreased the dopamine and serotonin levels in the prefrontal cortex (PFC), hippocampus (HPC), and spinal cord of mice. The animals subjected to the reserpine fibromyalgia model also showed decreased paw withdrawal threshold (PWT) and increased the immobility time in the forced swimming test (FST). Genetic ablation of B1R or pharmacological blockade by selective kinin B1R antagonist R-715 (acute i.p. treatment) counteracted the mechanical allodynia and increased immobility time induced by reserpine. However, neither pharmacological nor genetic inhibition of B1R reversed monoamine depletion. Our data confirm that reserpine induced a fibromyalgia-like phenotype in mice and reiterated the role of B1R on acute coping behavior and nociception modulation.

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

“…All identified studies in this review utilizing FST produced indications of depression-like behavior in animals as a result of the model . However, several studies utilized FST as a sole measure of affect [38][39][40][41][42][43][44][45][46][47][48]. While FST is understood to evaluate behavioral despair, which may be related to concepts of learned helplessness [71], these should not be considered unconditionally when employed as a lone measure of affective function.…”

“…Many treatments were investigated in their ability to alleviate cognitive and affective manifestations in animals. In assessments where FST was the sole measure of affect, the following treatments were reported as effective in alleviating behavioral despair associated with the reserpine model of FMS: curcumin [38], Phα1β [39], laser irradiation [41], duloxetine or a duloxetine-gamma irradiation combination treatment [41], imipramine [43], I2R agonists [43], combination treatment with folic acid and melatonin [44], B1R receptor KO or selective antagonists [45], and Cur-IONPs [46]. In other affective measures of FMSlike pain, evidence has been provided for improvement with a variety of antidepressants, including imipramine [49,54,56], duloxetine [37], desvenlafaxine [37], amitryptiline [59], citalopram [66], vortioxetine [75], and fluoxetine [61,62].…”