Articles: neuropathic-pain.
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Amygdala is involved in processing of primary emotions and particularly its central nucleus (CeA) also in pain control. Here we studied mechanisms mediating the descending control of mechanical hypersensitivity by the CeA in rats with a peripheral neuropathy in the left hind limb. For drug administrations, the animals had a guide cannula in the right CeA and an intrathecal catheter or another guide cannula in the medullary raphe. ⋯ The results indicate that depending on the dose, glutamate in the CeA has a descending facilitatory or inhibitory effect on neuropathic pain hypersensitivity. Serotoninergic raphe neurons are involved in mediating both of these effects. Spinally, the 5-HT3 receptor contributes to the increase and the 5-HT1A receptor to the decrease of neuropathic hypersensitivity induced by amygdaloid glutamate.
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The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of neurological disorders including chronic pain and inflammatory diseases. Since α7 can function as a ligand-gated ion channel, drug development initially focused on ligands that were selective activators of the α7 ion channel. However, the best α7 drugs for chronic pain and inflammation indications may not be ion channel activators but rather "silent agonists", which bind to the receptor but preferentially induce non-conducting states that modulate signal transduction in non-neuronal cells. ⋯ The antinociceptive activity of NS6740 in these models was α7-dependent. In addition, NS6740 administration reversed pain-induced aversion, an important affective component of pain. The time and concentration dependence of the effects were consistent with NS6740 induction of PAM-insensitive non-conducting states, suggesting that signal transduction required for analgesia is accomplished by α7 receptors in that conformation.
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Pain is a commonly reported symptom following surgery that is more likely to occur in individuals psychologically distressed prior to surgery. Monitoring processing style, a cognitive tendency to focus on health-related threats, has been associated with increased reporting of somatic symptoms, but no studies have specifically addressed the link between this cognitive style and pain. This prospective clinical study aimed to investigate whether monitoring processing style predicted post-surgical pain in women undergoing breast surgery, controlling for pre-surgical psychological distress. ⋯ Pre-surgical monitoring processing style was an independent predictor of post-surgical neuropathic pain, even when accounting for pre-surgical psychological distress. Since the reduction of post-surgical pain is a key goal of healthcare, efforts should be made prior to breast cancer surgery to counsel and support individuals with high monitoring processing styles irrespective of their level of distress.
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Neuropathic and inflammatory pain promote a large number of persisting adaptations at the cellular and molecular level, allowing even transient tissue or nerve damage to elicit changes in cells that contribute to the development of chronic pain and associated symptoms. There is evidence that injury-induced changes in chromatin structure drive stable changes in gene expression and neural function, which may cause several symptoms, including allodynia, hyperalgesia, anxiety, and depression. Recent findings on epigenetic changes in the spinal cord and brain during chronic pain may guide fundamental advances in new treatments. Here, we provide a brief overview of epigenetic regulation in the nervous system and then discuss the still-limited literature that directly implicates epigenetic modifications in chronic pain syndromes.
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Review
Neural Markers of Neuropathic Pain Associated with Maladaptive Plasticity in Spinal Cord Injury.
Given the potential use of neural markers for the development of novel treatments in spinal cord pain, we aimed to characterize the most effective neural markers of neuropathic pain following spinal cord injury (SCI). ⋯ When analyzed together, the results of these studies seem to point out to a common marker of pain in SCI characterized by decreased cortical activity in frontal areas and possibly increased subcortical activity. These results may contribute to planning further mechanistic studies as to better understand the mechanisms by which neuropathic pain is modulated in patients with SCI as well as clinical studies investigating best responders of treatment.