Neuroscience
-
Pain is an ambiguous perception: the same pain stimulation can be perceived differently in different contexts, producing different experiences, ranging from mild to unbearable pain. It can be even experienced as a rewarding sensation within the appropriate context. Overall, placebo and nocebo effects appear to be very good models to understand how the psychosocial context modulates the experience of pain. ⋯ Conversely, a negative context can produce pain exacerbation and clinical worsening through the modulation of different systems, such as the activation of cholecystokinin and the deactivation of opioids and dopamine. In addition, when a therapy is delivered unbeknownst to the patient, its effects are reduced. A better understanding of the neurobiological underpinnings of the context-pain interaction is a challenge both for future pain research and for good clinical practice.
-
Chronic pain conditions are multifactorial disorders with a high frequency in the population. Their pathophysiology is often unclear, and treatment is inefficient. During the last 20years, genetic linkage analysis and association studies have made considerable strides toward identifying key molecular contributors to the onset and maintenance of chronic pain. ⋯ In rare familial monogenic pain conditions several strong-effect mutations have been identified. In contrast, the genetic landscape of common chronic pain conditions suggests minor contributions from a large number of single nucleotide polymorphisms representing different functional pathways. A comprehensive survey of up-to-date genetic association results reveals migraine and musculoskeletal pain to be the most investigated chronic pain disorders, in which nearly half of identified genetic variability alters neurotransmission pathways.
-
Migraine is the third most common disease worldwide, the most common neurological disorder, and one of the most common pain conditions. Despite its prevalence, the basic physiology and underlying mechanisms contributing to the development of migraine are still poorly understood and development of new therapeutic targets is long overdue. Until recently, the major contributing pathophysiological event thought to initiate migraine was cerebral and meningeal arterial vasodilation. ⋯ This review will discuss the potential contribution of the vasculature, specifically endothelial cells, to current neuronal mechanisms hypothesized to play a role in migraine. Hypothalamic activity, cortical spreading depression (CSD), and dural afferent input from the cranial meninges will be reviewed with a focus on how these mechanisms can influence or be impacted by blood vessels. Together, the data discussed will provide a framework by which vessels can be viewed as important potential contributors to migraine pathophysiology, even in light of the current uncertainty over the role of vasodilation in this disorder.
-
In recent years, the delta opioid receptor has attracted increasing interest as a target for the treatment of chronic pain and emotional disorders. Due to their therapeutic potential, numerous tools have been developed to study the delta opioid receptor from both a molecular and a functional perspective. ⋯ Here, we describe (1) the cell-based assays used to study the delta opioid receptor. (2) The features of several delta opioid receptor ligands, including peptide and non-peptide drugs. (3) The existing approaches to detect delta opioid receptors in fixed tissue, and debates that surround these techniques. (4) Behavioral assays used to study the in vivo effects of delta opioid receptor agonists; including locomotor stimulation and convulsions that are induced by some ligands, but not others. (5) The characterization of genetically modified mice used specifically to study the delta opioid receptor. Overall, this review aims to provide a guideline for the use of these tools with the final goal of increasing our understanding of delta opioid receptor physiology.
-
Major depressive disorder is a serious psychiatric condition associated with high rates of suicide and is a leading cause of health burden worldwide. However, the underlying molecular mechanisms of major depression are still essentially unclear. In our study, a non-targeted gas chromatography-mass spectrometry-based metabolomics approach was used to investigate metabolic changes in the prefrontal cortex of the learned helplessness (LH) rat model of depression. ⋯ Using multivariate and univariate statistical analysis, a total of 18 differential metabolites were identified after the footshock stress protocol. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis. "Amino Acid Metabolism, Molecule Transport, Small Molecule Biochemistry" was the most significantly altered network in the LH model. Amino acid metabolism, particularly glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, was significantly perturbed in the prefrontal cortex of LH rats.