Possible involvement of oxido-nitrosative stress induced neuro-inflammatory cascade and monoaminergic pathway: Underpinning the correlation between nociceptive and depressive behaviour in a rodent model

Background: Pain and depression are frequent co-morbid disorders. The prevalence rate of depression is several times higher in patients with chronic pain than in the general population but the mechanism underlying this association is unknown. A combination of interactions between neurotransmitters, neuropeptides, oxidative and nitrosative stress and cytokines are thought to take part in pathogenesis of pain as well as depression. Thus, the aim of the present study was two-fold, first to investigate the interplay between nociception and associated depression and second to investigate the protective potential of berberine against the reserpine-induced nociceptive and depressive behaviour and further to explore the role of oxidative-nitrosative stress mediated inflammatory cascade and apoptotic signalling pathway in this dyad. Methods and results: Nociception and associated depression were induced by administration of reserpine (1 mg/kg subcutaneous daily) for three consecutive days. This behavioural deficit was integrated with decrease in the biogenic amine (dopamine, norepinephrine and serotonin) levels along with increased substance P concentration, oxidative-nitrosative stress, inflammatory cytokines, NF-kappa beta and caspase-3 levels in different brain regions (cortex and hippocampus) of the reserpinised rats. Limitation: More studies are still warranted in similar rodent models of pain and depression, so, that the present findings can be further substantiated to establish the clinical effectiveness of berberine in a subset of patients suffering from pain as well as depression. Conclusion: The findings from the current study suggested that reserpine-induced neurochemical alterations and dysregulation of oxidative-nitrosative stress induced inflammatory cascade underlies the co-morbidity of nociceptive behaviour and associated depression in rats. (C) 2013 Elsevier B.V. All rights reserved,