To Inadvertent Vascular Placement of an Intrathecal Catheter: A Case Report.

Intrathecal drug delivery systems (IDDS) are a treatment option for patients with chronic nonmalignant pain and cancer pain. In this case report, we describe a patient in whom an intrathecal catheter was implanted into a blood vessel rather than into the subarachnoid cavity. A contrast agent was administered, and digital subtraction angiography (DSA) imaging suggested that the catheter was inserted into a blood vessel. The anterior spinal arteries and veins were verified on the ventral side of the spinal cord without interruption. To our knowledge, this is the first report of implantation of an IDDS catheter into a blood vessel.

Puerarin Attenuates Complete Freund's Adjuvant-Induced Trigeminal Neuralgia and Inflammation in a Mouse Model via Sirt1-Mediated TGF-ß1/Smad3 Inhibition.

BACKGROUND: Puerarin, an active compound of radix puerariae, is a major compound used in Chinese herbal medicines and it has been well known for its pharmacological effects, including antioxidant, anti­inflammatory, neuroprotective and cardioprotective properties. The aim of the present study was to determine the role of puerarin (Pue) in complete Freund's adjuvant (CFA)-induced trigeminal neuralgia (TN) and the effects of this compound on Sirt1 activity and on the progression of CFA-induced TN. METHODS: Mice were injected with CFA on the unilateral face to induce TN. A cell model of inflammation-associated TN was established by interleukin-1ß (IL-1ß; 10 ng/mL) and tumor necrosis factor-α (TNF-α; 50 ng/mL) stimulation of neurons. Reverse transcription-quantitative PCR and Western blot analyses were performed to analyze mRNA and protein expression levels in trigeminal ganglion and nerve cells. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was used to determine nerve cell apoptosis following IL-1ß/TNF-α or Pue treatment. RESULTS: Pue is a conceivable Sirtuin1 (Sirt1) activator used for the prevention of trigeminal nerve injury that attenuates CFA-induced TN and inflammatory cytokine-evoked overactivation of neuronal inflammation and apoptosis. Treatment of mice with inflammatory cytokines induced upregulation of cleaved caspase-3 protein expression, which was neutralized by Pue supplementation. Both in vivo and in vitro experiments led to the conclusion that Pue modulated Sirt1 activation and repressed transforming growth factor-ß1 (TGF-ß1) protein expression and drosophila mothers against decapentaplegic homolog3 (Smad3) phosphorylation in order to exert neuroprotection. CONCLUSION: The findings suggested that Pue functioned as a potential Sirt1 activator to improve neuroinflammation-induced TN and neuronal apoptosis via the suppression of TGF-ß1/Smad3 activity. The pharmacological activity of Pue provides a new perspective for the effective prevention and treatment of TN.

Gastrodia elata Blume Polysaccharides Attenuate Vincristine-Evoked Neuropathic Pain through the Inhibition of Neuroinflammation.

Vincristine (Vin) is a well-known antitumor agent that frequently evokes neuropathic pain and decreases the quality of life of patients. Polysaccharides (GBP) extracted from Gastrodia elata Blume have been demonstrated to possess anti-inflammatory and neuroprotective effects in vivo; however, the effects of GBP on Vin-induced neuropathic pain remain unknown. The present study is aimed at exploring the alleviative potential of GBP against chemotherapy-evoked peripheral neuropathy to better understand and extend its pharmacological application. Vin was administered intraperitoneally to evoke neuropathic pain. GBP was orally administered for 21 days. The mechanical allodynia and thermal hyperalgesia were assessed using the Von Frey test and hot-plate test. Histopathological changes were assessed by hematoxylin and eosin staining. ELISA kits were used to measure the levels of inflammatory cytokines in the sciatic nerve, spinal cord, and dorsal root ganglion (DRG). qRT-PCR was employed to examine the expression of inflammatory cytokines and Sirtuin1 (SIRT1) in the sciatic nerve, spinal cord, and DRG. Our findings revealed that GBP treatment enhanced the paw withdrawal latency and paw withdrawal threshold and restored Vin-induced sciatic nerve damage in rats. GBP also attenuated the Vin-induced increase of proinflammatory cytokine levels, including IL-6, IL-8, TNF-α, IL-1ß, and NF-κB. On the molecular level, treatment with GBP downregulated the mRNA levels of IL-6, IL-8, TNF-α, and IL-1ß in the sciatic nerve, spinal cord, and DRG. Meanwhile, GBP increased SIRT1 activity and mRNA expression levels. Our data indicated that GBP exerted a potential protective effect against chemotherapy-induced neuropathic pain which might be mediated via the inhibition of neuroinflammation.

Puerarin alleviates vincristine-induced neuropathic pain and neuroinflammation via inhibition of nuclear factor-κB and activation of the TGF-ß/Smad pathway in rats.

Chemotherapy-induced neuropathic pain harms the quality of life patients. Vincristine is an often used chemotherapeutic drug that evokes neuralgia via inflammation. Puerarin (Pue) extracted from Puerariae Lobatae Radix has analgesic and anti-inflammatory effects; however, its possible effect and mechanism in vincristine (Vin)-induced neuropathic pain has not been investigated. The present research aimed to explore whether Pue could relieve chemotherapy-evoked neuropathic pain and the underlying mechanism actions. Rat neuropathic pain was established by intraperitoneal injection of vincristine. Pue was orally administered in two dose levels (25 or 50 mg/kg/d) for three weeks. The paw withdrawal latency and paw withdrawal threshold were performed to evaluate the pain behaviors. Inflammatory cytokines in the spinal cord and dorsal root ganglion were measured by ELISA kits. qRT-PCR, western blot, and immunofluorescence staining were employed to measure the level and expression feature of inflammatory cytokines. Our findings showed that Pue improved hyperalgesia and allodynia. Treatment with Pue restored the levels of tumor necrosis factor-α (TNF-α), and IL-1ß and increased the levels of transforming growth factor-ß (TGF-ß), and interleukin-10 (IL-10). On the molecular level, treatment with Pue down-regulated the protein levels of IL-1ß, and NF-κBp65 and up-regulated the protein levels of TGF-ß, p-Smad2, and p-Smad3 (TGF-ß/Smad) in the spinal cord and DRG. Immunofluorescence staining further demonstrated that Pue decreased the NF-κBp65 protein. Our findings imply that Pue relieved chemotherapy-induced neuropathic pain might be attributable to the suppression of inflammation cytokines. The anti-inflammation action of Pue might be associated with the activation of the TGF-ß/Smad pathway, a novel mechanism exploring its prophylactic effect in vincristine-induced neuropathic pain.

A Transcriptomic Analysis of Neuropathic Pain in Rat Dorsal Root Ganglia Following Peripheral Nerve Injury.

The aim of this work is to provide a comprehensive and unbiased understanding at the molecular correlates of peripheral nerve injury. In this study, we screened the differentially expressed genes (DEGs) in the DRG from rats using RNA-seq technique. Moreover, the bioinformatics methods were used to figure out the signaling pathways and expression regulation pattern of the DEGs enriched in. In addition, quantitative real-time RT-PCR was carried out to further confirm the expression of DEGs. 414 genes were upregulated, while 184 genes were downregulated in the DRG of rats 7 days after partial sciatic nerve ligation (pSNL) surgery. Moreover, GO and KEGG enrichment analysis suggested that most of the altered genes were involved in inflammatory responses and signaling transduction. In addition, our results state that they shared similar characters in the DRG among four types of neuropathic pain models. Eighteen genes have been altered (17 of them were upregulated) in the DRG of all four types of neuropathic pain models, in which Vgf, Atf3, Cd74, Gal, Jun, Npy, Serpina3n, and Hspb1 have been reported to be involved in neuropathic pain. Quantitative real-time RT-PCR results further confirmed the mRNA expression levels of Vgf, Atf3, Cd74, Gal, Jun, Npy, Serpina3n, and Hspb1 in the DRG of rats with pSNL surgery. The present study suggested that these eight genes may play important roles in neuropathic pain, revealing that these genes might serve as therapeutic targets for neuropathic pain. Moreover, anti-inflammatory therapy might be an effective approach for neuropathic pain treatment and prevention.

TRPV1 and spinal astrocyte activation contribute to remifentanil-induced hyperalgesia in rats.

Remifentanil is an ultra-short-acting µ-opioid receptor agonist, which is widely used in general anesthesia. However, comparing with other opioids, remifentanil often induces hyperalgesia. Accumulating evidence suggests that the transient receptor potential (TRP) channels and glial cells activation were involved in the development of neuropathic pain and hyperalgesia. However, whether the TRP channels and glial cells contribute to remifentanil-induced hyperalgesia is still unknown. In this study, we used the hot-plate and Von Frey tests to evaluate the thermal and mechanical hyperalgesia. Protein expressions of TRPV1 and protein kinase C (PKC) in dorsal root ganglion were assayed by western blotting and mRNA level of Trpv1, Trpa1, Trpv4, and Trpm8 were assayed by real-time PCR. TNF-α, IL-1ß, and IL-6 levels in spinal cord were measured by ELISA. Immunofluorescence assay was applied to analyze the activation of astrocyte in spinal cord. Continuing infusion of remifentanil induced thermal hyperalgesia and mechanical allodynia, which were accompanied by upregulation of TRPV1 and PKC protein in dorsal root ganglion. Moreover, remifentanil also increased the TNF-α, IL-1ß, and IL-6 levels and activates the astrocyte in spinal cord. Our findings suggested that TRPV1 is involved in the TRPV1-PKC signaling pathway, which contributes to the persistence of remifentanil-induced postoperative hyperalgesia. In addition, the spinal astrocyte activation and inflammatory reaction are involved in the remifentanil-induced postoperative hyperalgesia.

Bibliometric Analysis of Scientific Publications on Spinal Cord Stimulation in the Past Two Decades.

BACKGROUND: Spinal cord stimulation (SCS), a common invasive neuromodulation technique, induces pain relief via electrical stimulation of the dorsal column of the spinal cord. To present an overview of research publications on SCS, a bibliometric analysis of scientific publications from 1998 to 2017 was performed. METHODS: The relevant data were obtained from the Web of Science and PubMed database. These articles were classified into several categories, such as total number, countries, institutions, authors, and citations reports. The analysis of co-occurrence key words was handled by VOSviewer software. RESULTS: We found that there existed an increasing trend in the number of publications on SCS between 1998 and 2017. Among these countries, the United States published the largest number of papers in the past 20 years. Case Western Reserve University in the United States contributed the most publications. Among all research categories, neuroscience neurology was the most common area. In addition, regarding article types, basic research comprised a great proportion of the total papers on SCS in the PubMed database. The author V. Reggie Edgerton from the United States was the most-frequent contributor among the authors. The results showed that "spinal cord," "stimulation," and "pain" were the most common key words in the past 20 years. CONCLUSIONS: This bibliometric analysis first provides a basic overview of research publications on SCS published during the last 2 decades. Considering the expanded indications of SCS, there are a lot of things to do, and various countries should increase support to complete high-quality SCS studies.

Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury.

Puerarin is a major active ingredient of the traditional Chinese plant medicine, Radix Puerariae, and commonly used in the treatment of myocardial and cerebral ischemia. However, the effects of puerarin on neuropathic pain are still unclear. In this study, a neuropathic pain animal model was created by partial sciatic nerve ligation. Puerarin (30 or 60 mg/kg) was intraperitoneally injected once a day for 7 days. Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment. Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats, especially at 7 days after model establishment. At 7 days after model establishment, quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed mRNA expression of transient receptor potential vanilloid 1 (Trpv1) and transient receptor potential ankyrin 1 (Trpa1) in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury. These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.