Articles: neuralgia.
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Spinal D-serine plays an important role in nociception via an increase in phosphorylation of the N-Methyl-D-aspartate (NMDA) receptor GluN1 subunit (pGluN1). However, the cellular mechanisms underlying this process have not been elucidated. Here, we investigate the possible role of neuronal nitric oxide synthase (nNOS) in the D-serine-induced potentiation of NMDA receptor function and the induction of neuropathic pain in a chronic constriction injury (CCI) model. ⋯ In naïve mice, exogenous D-serine increased NO levels via decreases in pnNOS. D-serine-induced increases in mechanical hypersensitivity, NO levels, PKC-dependent pGluN1, and NMDA-induced spontaneous nociception were reduced by pretreatment with the nNOS inhibitor, 7-nitroindazole or with the NMDA receptor antagonists, 7-chlorokynurenic acid and MK-801. Collectively, we show that spinal D-serine modulates nNOS activity and concomitant NO production leading to increases in PKC-dependent pGluN1 and ultimately contributing to the induction of mechanical allodynia following peripheral nerve injury.
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Sensitivity to different pain modalities has a genetic basis that remains largely unknown. Employing closely related inbred mouse substrains can facilitate gene mapping of nociceptive behaviors in preclinical pain models. We previously reported enhanced sensitivity to acute thermal nociception in C57BL/6J (B6J) versus C57BL/6N (B6N) substrains. ⋯ Using a B6J × B6N-F2 cross (N = 164), we mapped a major quantitative trait locus underlying hot plate sensitivity to chromosome 7 that peaked at 26 Mb (log of the odds [LOD] = 3.81, p < 0.01; 8.74 Mb-36.50 Mb) that was more pronounced in males. Genes containing expression quantitative trait loci associated with the peak nociceptive marker that are implicated in pain and inflammation include Ryr1, Cyp2a5, Pou2f2, Clip3, Sirt2, Actn4, and Ltbp4 (false discovery rate < 0.05). Future studies involving positional cloning and gene editing will determine the quantitative trait gene(s) and potential pleiotropy of this locus across pain modalities.
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Stereotact Funct Neurosurg · Jan 2019
ReviewNeurosurgeons' Armamentarium for the Management of Refractory Postherpetic Neuralgia: A Systematic Literature Review.
Postherpetic neuralgia (PHN) can be refractory to both medical and minimally invasive treatments. Its complex pathophysiology explains the numerous neurosurgical procedures that have been implemented through the years. Our objective was to summarize all available neurosurgical strategies for the management of resistant PHN and evaluate their respective safety and efficacy outcomes. ⋯ There are several available neurosurgical approaches for recalcitrant PHN including neuromodulatory and ablative procedures. It is suggested that patients with resistant PHN undergo minimally invasive procedures first, including SCS, peripheral nerve stimulation or DRG radiofrequency lesioning. More invasive procedures should be reserved for refractory cases. Comparative studies are needed in order to construct a PHN neurosurgical management algorithm.
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Neuropathic pain is a common presenting complaint of patients with peripheral neuropathy (PN) and is considered one of the most disabling neuropathic symptoms, with detrimental effects on patients' quality of life (QoL). The aim of this review was to overview the current literature that focuses on QoL in painful PN of various aetiologies. We sought to clarify the direct effect of pain and its treatment on patients' QoL. ⋯ The findings demonstrate that QoL is impaired in painful PN and should not be neglected in clinical practice. Patients' pain management and subsequent impact on QoL should routinely be assessed and monitored.
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Randomized Controlled Trial Multicenter Study
Dextromethorphan and memantine after ketamine analgesia: a randomized control trial.
Intravenous ketamine is often prescribed in severe neuropathic pain. Oral N-methyl-D-aspartate receptor (NMDAR) antagonists might prolong pain relief, reducing the frequency of ketamine infusions and hospital admissions. This clinical trial aimed at assessing whether oral dextromethorphan or memantine might prolong pain relief after intravenous ketamine. ⋯ Oral dextromethorphan given after ketamine infusion extends pain relief during one month and could help patients to better cope with pain. Future studies should include larger populations stratified on pharmacogenetics screening. Optimization of an oral drug that could extend ketamine antihyperalgesia, with fewer hospital admissions, remains a prime challenge in refractory neuropathic pain.