BackgroundVoltage-gated sodium channels Nav1.8 and Nav1.9 are expressed preferentially in small diameter sensory neurons, and are thought to play a role in the generation of ectopic activity in neuronal cell bodies and/or their axons following peripheral nerve injury. The expression of Nav1.8 and Nav1.9 has been quantified in human lingual nerves that have been previously injured inadvertently during lower third molar removal, and any correlation between the expression of these ion channels and the presence or absence of dysaesthesia investigated.ResultsImmunohistochemical processing and quantitative image analysis revealed that Nav1.8 and Nav1.9 were expressed in human lingual nerve neuromas from patients with or without symptoms of dysaesthesia. The level of Nav1.8 expression was significantly higher in patients reporting pain compared with no pain, and a significant positive correlation was observed between levels of Nav1.8 expression and VAS scores for the symptom of tingling. No significant differences were recorded in the level of expression of Nav1.9 between patients with or without pain.ConclusionsThese results demonstrate that Nav1.8 and Nav1.9 are present in human lingual nerve neuromas, with significant correlations between the level of expression of Nav1.8 and symptoms of pain. These data provide further evidence that changes in expression of Nav1.8 are important in the development and/or maintenance of nerve injury-induced pain, and suggest that Nav1.8 may be a potential therapeutic target.

No abstract

HighlightsWe identified XCR1 in the peripheral and central nervous systems and demonstrated its upregulation following nerve injury.In injured nerve, XCR1 is present in nerve fibers, CD45-positive leucocytes and Schwann cells.In Vc, XCR1 labeling is consistent with expression in terminals of Aδ- and C-fiber afferents and excitatory interneurons.XCL1 increases neuronal excitability and activates intracellular signaling in Vc, a pain-processing region of the CNS.These data provide the first evidence that the XCL1-XCR1 axis may play a role in trigeminal pain pathways.

Background Peripheral nerve injury causes changes in expression of multiple receptors and mediators that participate in pain processing. We investigated the expression of microRNAs (miRNAs) – a class of post-transcriptional regulators involved in many physiological and pathophysiological processes – and their potential role in the development or maintenance of chronic neuropathic pain following lingual nerve injury in human and rat. Methods We profiled miRNA expression in Sprague-Dawley rat and human lingual nerve neuromas using TaqMan® low-density array cards. Expression of miRNAs of interest was validated via specific probes and correlated with nerve injury-related behavioural change in rat (time spent drinking) and clinical pain (visual analogue scale (VAS) score). Target prediction was performed using publicly available algorithms; gene enrichment and pathway analysis were conducted with MetaCore. Networks of miRNAs and putative target genes were created with Cytoscape; interaction of miRNAs and target genomes in rat and human was displayed graphically using CircosPlot. Results rno-miR-138 was upregulated in lingual nerve of injured rats versus sham controls. rno-miR-138 and rno-miR-667 expression correlated with behavioural change at day 3 post-injury (with negative (rno-miR-138) and positive (rno-miR-667) correlations between expression and time spent drinking). In human, hsa-miR-29a was downregulated in lingual nerve neuromas of patients with higher pain VAS scores (painful group) versus patients with lower pain VAS scores (non-painful). A statistically significant negative correlation was observed between expression of both hsa-miR-29a and hsa-miR-500a, and pain VAS score. Conclusions Our results show that following lingual nerve injury, there are highly significant correlations between abundance of specific miRNAs, altered behaviour and pain scores. This study provides the first demonstration of correlations between human miRNA levels and VAS scores for neuropathic pain and suggests a potential contribution of specific miRNAs to the development of chronic pain following lingual nerve injury. Putative targets for candidate miRNAs include genes related to interleukin and chemokine receptors and potassium channels.

No abstract

No abstract

Some of the sensory abnormalities that follow peripheral nerve injury may result from the development of ectopic discharge from the damaged axons. Previous studies in our laboratory have shown that, following tight ligation of the inferior alveolar nerve (IAN), there is a close association between the time-course of this neural activity and the accumulation of neuropeptides at the injury site. In this study we investigated whether the type of injury has any effect on the time-course or level of neuropeptide expression. In 36 adult ferrets, the IAN was either loosely constricted or sectioned, and the animals left to recover for 3 days, 3 weeks, or 3 months. The tissue was processed using indirect immunofluorescence and image analysis was used to quantify levels of substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, enkephalin, galanin, and neuropeptide Y. Immunoreactivity to all of the neuropeptides was present within the injured nerve 3 days after both types of injury, and decreased to lower levels by 3 weeks and 3 months. Comparisons between the levels of neuropeptide immunoreactivity in each group revealed that the pattern of accumulation was similar following loose constriction or section, and also similar to that found in our previous study on tight ligation. For each injury the time-course of neuropeptide expression was similar to that of the spontaneous activity we had previously recorded. These data support the suggestion that neuropeptide accumulation may be linked to the development of ectopic neural activity but indicate that the type of injury has little effect on the extent of expression.