Emotional consequences of neuropathic pain: Insight from preclinical studies

Mood disorders such as depression and anxiety are frequently observed in patients suffering from chronic pain, including neuropathic pain. While this comorbidity is clinically well established, the underlying mechanism(s) remained unclear. The recent development of animal models now allows addressing the consequences of neuropathic pain. In this review, we report the preclinical evidences from anatomical, neuroimaging, behavioral, pharmacological and biochemical studies that address the anxiodepressive consequences of neuropathic pain. We present an overview of rodent models of these consequences and we discuss the challenges and parameters to consider for generating these models. We then discuss the possible mechanism(s) underlying anxiodepressive consequences by describing morphological and functional changes. Information is provided concerning neuroanatomical changes and plasticity, including LTP and LTD, in the anterior cingulate cortex, the insula, the hippocampus, the amygdala and the mesolimbic system, neuroendocrine parameters concerning the hypothalamo-pituitary-adrenal axis, neuroimmune response including the role of glial cells and cytokines, monoamine systems and changes in locus coeruleus noradrenergic system, and neurotrophic factors such as BDNF.