Articles: neuralgia.
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P2X4 is a ligand-gated ion channel implicated in neuropathic pain. Drug discovery efforts targeting P2X4 have been unsuccessful largely because of the difficulty in engineering specificity and selectivity. Here, we describe for the first time the generation of a panel of diverse monoclonal antibodies (mAbs) to human and mouse P2X4, capable of both positive and negative modulation of channel function. ⋯ Site-directed mutagenesis of P2X4 revealed the head domain as a key interaction site for inhibitory mAbs. Inhibition of spinal P2X4 either by intrathecal delivery of an anti-P2X4 mAb or by systemic delivery of an anti-P2X4 bispecific mAb with enhanced blood-spinal cord barrier permeability produced long-lasting (>7 days) analgesia in a mouse model of neuropathic pain. We therefore propose that inhibitory mAbs binding the head domain of P2X4 have therapeutic potential for the treatment of neuropathic pain.
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Neurochemical research · Sep 2019
N-methyl-D-aspartate Receptors in the Prelimbic Cortex are Critical for the Maintenance of Neuropathic Pain.
The mechanisms underlying chronic and neuropathic pain pathology involve peripheral and central sensitisation. The medial prefrontal cortex (mPFC) seems to participate in pain chronification, and glutamatergic neurotransmission may be involved in this process. Thus, the aim of the present work was to investigate the participation of the prelimbic (PrL) area of the mPFC in neuropathic pain as well as the role of N-methyl D-aspartate (NMDA) glutamate receptors in neuropathic pain induced by a modified sciatic nerve chronic constriction injury (CCI) protocol in Wistar rats. ⋯ Mechanism of neuropathic pain. The infusion of CoCl2, a synapse activity blocker, into the prelimbic (PrL) division of the medial prefrontal cortex (mPFC) decreased the severity of mechanical allodynia, showing the late participation of the limbic cortex. The glutamatergic system potentiates chronic neuropathic pain via NMDA receptor activation in the PrL cortex.
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Purpose: This study aimed to characterize the sensory profile of patients with post-implant trigeminal neuropathy and identify the association between subjective symptoms and objective signs including psychophysical testing and radiographic imaging. This study further evaluated to the association between quantitative sensory testing (QST)/qualitative sensory testing (QualST) and the severity of nerve injury graded by radiographic imaging. Materials and methods: This retrospective study included 34 patients diagnosed with post-implant trigeminal neuropathy. ⋯ Moderate positive correlations between some positive symptoms and the score of QualST were observed. The Mann-Whitney U test showed that subjective symptoms did not differ according to the severity of nerve damage according to CBCT, but the electric QST and QualST was discriminative. Conclusions: This study suggests that QST/QualST associated with the severity of nerve damage according to CBCT might be useful in assessing numbness in patients with negative and positive symptoms after implant surgery, but may be of marginal utility in the evaluation of neuropathic pain within the limitation of this cross-sectional study with small sample size.
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Postgraduate medicine · Sep 2019
Observational StudySmall fiber neuropathy in coeliac disease and gluten sensitivity.
Objectives: The commonest types of peripheral neuropathy in the context of Coeliac Disease (CD) and gluten sensitivity (GS) are length-dependent symmetrical sensorimotor neuropathies and sensory ganglionopathies. In patients with such neuropathy, (gluten neuropathy), peripheral neuropathic pain is prevalent suggesting involvement of small fibers. The purpose of this report was to describe the clinical characteristics of patients with CD or GS and pure small fiber neuropathy (SFN). ⋯ In 8 patients (61.5%) pain was the presenting feature. Neurophysiological assessment suggested a length-dependent small fiber neuropathy in 11 patients, whereas in 2, a non-length dependent pattern was identifying suggesting that the predominant pathology lies in the dorsal root ganglia. Conclusion: SFN can be a presenting feature of CD and GS and, therefore, screening for CD and GS should be included in the diagnostic workup of patients with idiopathic SFN.