Junzhen Wu

Brain-derived neurotrophic factor–activated astrocytes produce mechanical allodynia in neuropathic pain

Neuropathic pain management is challenging for physicians and a vexing problem for basic researchers. Recent studies reveal that activated spinal astrocytes may play a vital role in nerve injury-induced neuropathic pain, although the mechanisms are not fully understood. We have found increased glial fibrillary acidic protein (GFAP) expression, a hallmark of reactive gliosis, and elevated brain-derived neurotrophic factor (BDNF) expression in the dorsal horn in a rat model of allodynia induced by spinal nerve ligation (SNL). The high GFAP expression and mechanical allodynia that SNL induces were prevented by the intrathecal injection of the BDNF-sequestering fusion protein TrkB/Fc. Additionally, mechanical allodynia and GFAP overexpression was induced by the spinal administration of exogenous BDNF to naive rats, and exogenous BDNF given together with fluorocitrate, an astrocytic metabolism inhibitor, inhibited allodynia and GFAP upregulation. Exogenous BDNF also activated the astrocytes directly when tested in vitro. Furthermore, intrathecal administration of BDNF-stimulated astrocytes also induced mechanical allodynia in naive rats. All of these results indicate that astrocytes activated by BDNF might contribute to mechanical allodynia development in neuropathic pain in rats.

Minocycline attenuates mechanical allodynia and expression of spinal NMDA receptor 1 subunit in rat neuropathic pain model

Recent studies have indicated that minocycline, a microglia inhibitor, could potentially be used as an antinociceptive agent in pain management, although the underlying mechanisms remain elusive. In this study, we investigated the extent to which minocycline could influence pain behavior in association with the expression of the N-methyl-d-aspartic acid receptor 1 (NMDAR1) in a rat L5 spinal nerve ligation (SNL) model. We observed that the intrathecal injection of minocycline significantly attenuated mechanical allodynia in a rat SNL model from dayxa01 postinjection and persisted for at least 18xa0days. We also observed that the expression of NMDAR1 was increased in the spinal dorsal horn at 8xa0days after SNL, which could be partly inhibited through the intrathecal injection of minocycline. These findings suggest that the attenuation of allodynia in the SNL model following minocycline administration might be associated with the inhibited expression of NMDAR1 and, therefore, might play an important role in the minocycline-mediated antinociception.

p38/MAPK inhibitor modulates the expression of dorsal horn GABA(B) receptors in the spinal nerve ligation model of neuropathic pain.

Background: Neuropathic pain is one of the most challenging clinical problems due to a lack of understanding the mechanisms. Recent studies have suggested that activated microglia in spinal cord may play a vital role in nerve injury-induced neuropathic pain, but the exact mechanisms have not been fully determined. Methods: First, we investigated the changes of dorsal horn GABA(B) receptor 1 (R1) expression in spinal nerve ligation rats. Second, we explored whether activated microglia contributed to such neuron changes by intrathecal administration of the p38 inhibitor, SB203580. Results: In this study, we found a dynamic change of GABA(B)R1a protein expression after spinal nerve ligation, and the peripheral nerve injury-induced downregulation of GABA(B)R1a expression in the spinal dorsal horn could be prevented by intrathecal administration of a p38/MAPK inhibitor SB203580. Conclusions: Our results provide valuable information for a better understanding of neuropathic pain and may contribute to developing effective treatments in future studies.

Circulating microRNA expression profile: a novel potential predictor for chronic nervous lesions

The mechanisms of chronic neuropathic pain are not clear. Serum microRNAs (miRNAs) might show a special feature for chronic nervous lesions. However, little is known about the changes in circulating miRNAs for the neuropathic pain. Therefore, changes in the circulating miRNAs expression profile for the neuropathic pain were investigated. Serum was collected from rats before and after spinal nerve ligation (SNL) surgery, and a microarray analysis was performed to determine the changes in miRNA expression profile. The expression of inflammatory cytokines in serum from the same individuals, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), was also measured. The results showed that the expression levels of IL-6, TNF-α, and MCP-1 were significantly elevated in SNL rats which were significantly correlated with pain levels. Nine miRNAs with significantly different expression levels before and after SNL surgery were identified by microarray analysis, which were further validated by quantitative real-time polymerase chain reaction analyses. Compared with naive rats without SNL surgery, the expression of five miRNAs (hsa-miR-221, hsa-miR-34c, hsa-miR-21, hsa-miR-30a-5p, and hsa-miR-206) in the serum of rats after SNL surgery was decreased and four miRNAs (hsa-miR-31-5p, hsa-miR-133b, hsa-miR-22, and hsa-miRPlus-A1087) were increased, suggesting that miRNA changes may involve in the regulation of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs, and the results showed that the transcripts with multiple predicted target sites belonged to neurologically important pathways. Bioinformatics analysis revealed that several target genes are related to the activation of cell signaling associated with nervous lesions. In this study, the changes to miRNA profiles in serum under neuropathic pain conditions were shown for the first time, suggesting that circulating miRNAs profile in serum is a potential predictor for neuropathic pain.

Effects of ultrasound-guided stellate ganglion block on cervical vascular blood flow: study protocol for a randomized controlled trial

BackgroundThe stellate ganglion block (SGB) can lead to vasodilation of the head and neck. However, controversy remains concerning the changes in extracerebral blood flow. The objective of this study is to assess the effects of SGB on the blood flow to the neck.MethodsA randomized controlled crossover trial with 38 participants will be conducted. Participants who have primary headaches will be assigned to either group A or B. Patients in group A will receive SGB with 6xa0ml 1% lidocaine, and after a one-week washout period, they will undergo the second SGB with 6xa0ml normal saline. In contrast, patients in group B will receive the opposite protocol. Data will be collected at baseline (T0) and at 15xa0min after the first intervention (T1), 15xa0min before the second intervention (T2), 15xa0min after the second intervention (T3) and at a 3-week follow up (T4). T1 is the primary time point for the primary outcome analysis. The primary outcomes include the peak systolic velocity (PSV), the end diastolic velocity (EDV), resistance index (RI) and vessel diameter of the common carotid artery (CCA) and vertebral artery (VA). The secondary outcomes include the rate of ptosis, the rate of conjunctival flushing, and the numerical rating scale (NRS) pain score. Additionally, adverse events (AEs) or serious adverse events (SAEs) will be collected at each assessment point.DiscussionThis study will comprehensively investigate the efficacy of SGB in extracerebral blood flow. Our research may also suggest that SGB will be effective in reducing pain in patients with primary headaches.Trial registrationChinese Clinical Trial Registry, identifier ChiCTR-IOR-17011536. Registered on 1 June 2017.