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

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.

Neuroendocrine and Neurochemical Processes in Depression

Neuroendocrine and neurochemical theories of depression have continued to be of importance in understanding pathophysiology and suggesting new kinds of pharmacological interventions. Monoamine theories still dominate the neurochemistry of depression and results from monoamine depletion studies suggest that in certain circumstances lowered activity of serotonin and noradrenaline pathways can indeed lead to clinical depressive symptomatology. More recent developments have implicated changes in the amino acid neurotransmitters γ-aminobutyric acid (GABA) and glutamate in depressed patients; the ability of the N-methyl-d-aspartate acid (NMDA) receptor antagonist, ketamine, to relieve depressive symptomatology rapidly has spurred basic research on the cellular mechanism of glutamatergic antidepressant action. The link between inflammation and depression has led to new kinds of immunological investigations in depressed patients and suggests the possibility of developing effective targeted antiinflammatory treatments. Finally hypothalamic–pituitary–adrenal (HPA) axis abnormalities remain a focus of interest, particularly in the context of the many medical comorbidities that frequently complicate chronic depressive disorders.