What is the central question of this study? Is peripheral sensory function impaired in the chronic phase of non-freezing cold injury (NFCI)? What is the main finding and its importance? Warm and mechanical detection thresholds are elevated and intraepidermal nerve fibre density is reduced in individuals with NFCI in their feet when compared to matched controls. This indicates impaired sensory function in individuals with NFCI. Interindividual variation was observed in all groups, and therefore a diagnostic cut-off for NFCI has yet to be established.
View Article and Find Full Text PDFBackground And Objectives: The mechanisms of pain in patients with diabetic polyneuropathy are unknown. Studies have suggested a role of inflammation and increased neuropeptides peripherally in pain generation. This study examined the possible skin markers of painful diabetic polyneuropathy (P-DPN): macrophages, substance P (SP), and calcitonin gene-related peptide (CGRP).
View Article and Find Full Text PDFIn neurodegenerative conditions and following brain trauma it is not understood why neurons die while astrocytes and microglia survive and adopt pro-inflammatory phenotypes. We show here that the damaged adult brain releases diffusible factors that can kill cortical neurons and we have identified histone H1 as a major extracellular candidate that causes neurotoxicity and activation of the innate immune system. Extracellular core histones H2A, H2B H3 and H4 were not neurotoxic.
View Article and Find Full Text PDFBortezomib (BTZ) is the first proteasome inhibitor entered in clinical practice. Peripheral neuropathy is likely to be a class side effect of these drugs, although its severity is largely variable, and it deserves to be further investigated, since the mechanisms of BTZ-induced peripheral neurotoxicity (BiPN) are still unknown. In our study, we investigated in vivo and in vitro possible pathogenic events relevant to BiPN using a well-established rat model, with particular reference to the extent of proteasome inhibition and the effects on α-tubulin polymerization in sciatic nerves and dorsal root ganglia specimens obtained from animals treated with chronic regimens at a dose of 0.
View Article and Find Full Text PDFAxons and Schwann cells exist in a highly interdependent relationship: damage to one cell type invariably leads to pathophysiological changes in the other. Greater understanding of communication between these cell types will not only give insight into peripheral nerve development, but also the reaction to and recovery from peripheral nerve injury. The type III isoform of neuregulin-1 (NRG1) has emerged as a key signaling factor that is expressed on axons and, through binding to erbB2/3 receptors on Schwann cells, regulates multiple phases of their development.
View Article and Find Full Text PDFBackground: Chronic neuropathic pain is a common condition which is challenging to treat. Many people with neuropathic pain are managed in the community, so primary care records may allow more appropriate subjects to be recruited for clinical studies.
Objective: We investigated whether primary care records can be used to identify patients with diseases associated with neuropathic pain.