Role of PAF Receptor in Proinflammatory Cytokine Expression in the Dorsal Root Ganglion and Tactile Allodynia in a Rodent Model of Neuropathic Pain

BACKGROUND: Neuropathic pain is a highly debilitating chronic pain following damage to peripheral sensory neurons and is often resistant to all treatments currently available, including opioids. We have previously shown that peripheral nerve injury induces activation of cytosolic phospholipase A(2) (cPLA(2)) in injured dorsal root ganglion (DRG) neurons that contribute to tactile allodynia, a hallmark of neuropathic pain. However, lipid mediators downstream of cPLA(2) activation to produce tactile allodynia remain to be determined. PRINCIPAL FINDINGS: Here we provide evidence that platelet-activating factor (PAF) is a potential candidate. Pharmacological blockade of PAF receptors (PAFRs) reduced the development and expression of tactile allodynia following nerve injury. The expression of PAFR mRNA was increased in the DRG ipsilateral to nerve injury, which was seen mainly in macrophages. Furthermore, mice lacking PAFRs showed a reduction of nerve injury-induced tactile allodynia and, interestingly, a marked suppression of upregulation of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) expression in the injured DRG, crucial proinflammatory cytokines involved in pain hypersensitivity. Conversely, a single injection of PAF near the DRG of naïve rats caused a decrease in the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner and an increase in the expression of mRNAs for TNFalpha and IL-1beta, both of which were inhibited by pretreatment with a PAFR antagonist. CONCLUSIONS: Our results indicate that the PAF/PAFR system has an important role in production of TNFalpha and IL-1beta in the DRG and tactile allodynia following peripheral nerve injury and suggest that blocking PAFRs may be a viable therapeutic strategy for treating neuropathic pain

A clinical tool for predicting survival in ALS

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis. Methods: 575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval. Findings: Younger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median. Interpretation: A simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors

Comparison of neuropathic pain and neuronal apoptosis following nerve root or spinal nerve compression

Altered dorsal root ganglion (DRG) function is associated with neuropathic pain following spinal nerve injury. However, compression of the cauda equina and dorsal rhizotomy proximal to the DRG do not induce significant pain, whereas in the spinal nerve and peripheral nerve, injury distal to the DRG does induce neuropathic pain. Caspase signaling induces apoptosis, and caspase inhibitors prevent pain-related behavior. The degree of DRG neuronal apoptosis is thought to play a role in pain behavior. We suggest that differences in pain behavior according to the injury sites within the DRG may be related to imbalances in apoptotic injuries. The aim of this study was to determine which compression injury was more painful and to compare behavior with expression of tumor necrosis factor (TNF)-alpha in DRG and apoptosis in the DRG following crush injury to the L5 nerve root or L5 spinal nerve. Sprague–Dawley rats received a crush injury to the L5 spinal nerve (distal to the DRG), crush injury to the L5 nerve root (proximal to the DRG), or no crush injury (sham). Mechanical allodynia was determined by the von Frey test. Expression of TNF-alpha was compared among three groups using immunoblot findings. Furthermore, we compared the percentage of neurons injured in the DRG using immunostaining for apoptotic cells and localization of activated caspase 3. Mechanical allodynia was observed in both crush injury groups. The duration of mechanical allodynia in the distal crush group was significantly longer than in the proximal crush group (P < 0.05). TNF-alpha expression was increased in DRG neurons following injury. DRG apoptosis in the distal crush group was significantly higher than in the proximal group at each time point (P < 0.05). This study suggests that spinal nerve crush injuries produce a greater degree of DRG apoptosis than do corresponding nerve root crush injuries, and that the former injuries are associated with longer lasting mechanical allodynia. Thus, differences in the time course of mechanical allodynia might be associated with an imbalance in DRG apoptosis

2017年度読書運動プロジェクト活動報告書

活動資料 p.(1)～p.(5)はじめに : 藤本 朝巳 p.1読書会 : 三雲 紫恩、有馬 梨咲 p.2-p.3コンテスト・コンクール : 森園 佳子 p.4-p.6展示 : 山下 萌 p.7-p.10コラボランチ : 小根山 桃子 p.11選書ツアー : 中村 好花 p.12文学散歩 : 伊豆 美保 p.13他大学図書館訪問 : 津田 優里香 p.14大学祭 : 本釜 菜津子、林 陽子 p.15-p.17読み聞かせレッスン : 森園 佳子 p.18小学校朗読会 : 小野 紘子、三雲 紫恩 p.19-p.20朗読会 : 阿部 美彩 , 鈴木 珠友、穂積 優香、森園 佳子 p.21-p.24プロフィール p.25-p.32おわりに : 森園 佳子 p.33写真あり表あ

2018年度読書運動プロジェクト活動報告書

活動資料 p.(1)～p.(5)はじめに : 藤本 朝巳 p.1読書会 : 小根山 桃子、立原 優菜、三雲 紫恩 p.2-p.4コンテスト・コンクール : 森園 佳子 p.5-p.7展示 : 山下 萌 p.8-p.11コラボランチ : 社本 衣舞紀 p.12文学散歩 : 中村 好花 p.13選書ツアー : 津田 優里香、鈴木 綾紗 p.14-p.15泉区読書推進イベント : 森園 佳子、伊豆 美保、小林 すずな p.16-p.18絵本講座・読み聞かせ講座 : 森園 佳子 p.19大学祭 : 花房 若奈、林 陽子 p.20-p.22朗読会 : 小野 紘子、関口 恵奈、穂積 優香、三雲 紫恩、児玉 玲奈、平山 真由子、宇野 菜々春、小林 すずな p.23-p.29プロフィール : p.30-39おわりに : 森園 佳子 p.40写真あり表あ