Articles: neuralgia.
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Neuropathic pain is one of the most challenging types of pain to diagnose and treat, a problem exacerbated by the lack of a quantitative biomarker. Recently, several clinical and preclinical studies have shown that neuropathic pain induces cerebral hemodynamic changes as a result of neuroplasticity in the brain. Our hypothesis in this study is that neuropathic pain leads to cerebral hemodynamic changes over postoperative time in a spinal nerve ligation (SNL) rat model, which has not been longitudinally explored previously. ⋯ We investigate cerebral hemodynamic changes using dynamic susceptibility contrast magnetic resonance imaging in a rat model up to 28 days after ligating L5/L6 spinal nerves. We trained a linear support vector machine with relative cerebral blood volume data from different brain regions and found that the prediction model trained on the nucleus accumbens, motor cortex, pretectal area, and thalamus classified the SNL group and sham group at a 79.27% balanced accuracy, regardless of when the onset of pain occurred (SNL/sham: 60/45 data points). From the use of the SNL model without prior knowledge of the onset time of pain, the current findings highlight the potential of relative cerebral blood volume in the 4 highlighted brain regions as a biomarker for neuropathic pain.
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NCT02010281.
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Randomized Controlled Trial
E-52862-A selective sigma-1 receptor antagonist, in peripheral neuropathic pain: Two randomized, double-blind, phase 2 studies in patients with chronic postsurgical pain and painful diabetic neuropathy.
We report the efficacy and safety of E-52862-a selective, sigma-1 receptor antagonist-from phase 2, randomized, proof-of-concept studies in patients with moderate-to-severe, neuropathic, chronic postsurgical pain (CPSP) and painful diabetic neuropathy (PDN). ⋯ These proof-of-concept studies validate the mode of action of E-52862, a selective sigma-1 receptor antagonist. In CPSP, E-52862 resulted in clinically meaningful pain relief. In PDN, reductions in pain intensity were seen with E-52862; high placebo response rates may have prevented differentiation between E-52862 and placebo. These findings are clinically relevant given that neuropathic pain is highly incapacitating, lacking effective treatments and representing a significant unmet medical need, and support further development of sigma-1 receptor antagonists for peripheral neuropathic pain.
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Current clinical trials indicate that repetitive transcranial magnetic stimulation (rTMS) is effective in reducing drug-resistant neuropathic pain (NP). However, there is a lack of studies evaluating the long-term feasibility and clinical efficacy of rTMS in large patient cohorts in real-world conditions. ⋯ Multiple rTMS sessions demonstrate long-term efficacy and safety in treating drug-resistant neuropathic pain. Extending session numbers for the test period can enhance responder identification, especially in patients with initial low pain relief. This identification refines patient selection for neurosurgery, reducing non-responders. Central neuropathic pain shows higher success rates than peripheral. For post-stroke central pain, patients with ischemic stroke are more likely to respond than those with hemorrhagic stroke. These results support integrating rTMS into clinical practice for managing neuropathic pain.
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Pharmacological ablation of rostral ventromedial medulla (RVM) mu opioid receptor-expressing cells before peripheral nerve injury prevents the development of neuropathic pain. However, whether these neurons are required for the expression of established neuropathic pain is not known. Male Oprm1Cre heterozygous (MOR Cre ) or wild-type (MOR WT ) mice received AAV8-hSyn-DIO-hM4D(Gi)-mCherry in the RVM. ⋯ Sustained CNO in drinking water before PSNL prevented expression of chronic pain without affecting acute surgical pain; however, relief of chronic pain required sustained CNO treatment. Thus, in male mice, activity of spinally projecting RVM-MOR cells is required (1) for expression and manifestation of both sensory and affective dimensions of established neuropathic pain and (2) to promote descending facilitation that overcomes apparently intact descending inhibition to maintain chronic pain. Enhanced descending facilitation likely regulates the output signal from the spinal cord to the brain to shape the pain experience and may provide a mechanism for nonopioid management of pain.