關(guān)于氨基酸和神經(jīng)肽與疼痛關(guān)系的研究-預(yù)覽頁
【正文】 ation coefficient P value PI vs. glutamine Correlation coefficient P value *** PI vs. glycine Correlation coefficient P value *** PI vs. taurine Correlation coefficient P value ** PI – Pain intensity – graded as Mild輕度 (n = 11), Moderate 中度 (n = 18), Severe嚴(yán)重 (n = 9) * (P ) ** (P ) *** (P ) – Statistically significant correlation relative to the control group. CSF concentration of other amino acids not related to pain 與疼痛不相關(guān)的氨基酸在腦脊液中濃度 Amino acids Age (mean 177。mol/L) (n = 38) 177。 177。 177。 177。 177。 177。 177。 177。 SD) 年齡（平均數(shù) 177。mol/L) (n = 29) 177。 *** 177。 ??? 177。 Citrulline瓜氨酸 165。 GABA伽馬氨基丁酸 177。 ** 177。 ??? 177。 Taurine牛黃酸 177。 SEM。 mol/L Results ? Chronic pain Vs No pain group 慢性疼痛和無疼痛 Aspartate, glutamate, glycine and NO involved in chronic pain perception 天門冬氨酸鹽，谷氨酸，甘氨酸和一氧化氮與疼痛的感知有關(guān) ? Chronic pain Vs Acute pain – Differential roles of amino acids in chronic and acute pain states 慢性疼痛和急性疼痛 —氨基酸在慢性和急性疼痛狀態(tài)的不同作用 Aspartate a key player in pathogenesis of chronic pain 天門冬氨酸鹽 —導(dǎo)致慢性疼痛的重要因素 Future Scope前景 ? This simple CSF amino acid analysis method can be applied to study various other pain states and CNS diseases. 這種簡(jiǎn)易的氨基酸分析方法可以用于其它疼痛狀態(tài)和神經(jīng)系疾病分析 ? This method of CSF analysis without pretreatment in the presence of Triton can also be applied to other analysis procedures. 這種含有 Triton， 無預(yù)處理腦脊液分析方法可以用于其它分析方法中 ? With more number of age matched subjects (increase “n”) and with well defined pain conditions potential markers can be identified for each type of pain. 同樣年齡組中如果有足夠樣本 ， 在有明確的對(duì)疼痛定義的前提下 ， 對(duì)各種疼痛類型 ， 可以鑒別出潛在的生物標(biāo)記 Purification and characterization of peptides from CSF of chronic pain patients 慢性疼痛病人腦脊液中肽的提純和特性研究 Peptide Purification Strategy 肽的提純方法 Pooled CSF Preparative HPLC Fraction A Fraction B Fraction C Ultra filtration Analytical HPLC Microbore HPLC Staining, Digestion, MALDITOF MS MS sequencing Staining Identification鑒別 Characterisation特性 Quantification量化 Localisation 位置 CNS effects 在中樞神經(jīng)中的影響 Antagonists 對(duì)抗劑 Pain models疼痛原型 The Story …… ? 1973 – morphine binding sites / opiate receptors L Terenius, S Snyder, E Simon ? 1975 – enkephalin J Hughes, H Kosterlitz ? Papaver somniferum – pain, diarrhoea amp。 377: 53235 Reinscheid et al. Science 1995。412:3944 Modulation of synaptic transmission by nociceptin / orphanin FQ and nocistatin in the spinal cord dorsal horn of mutant mice lacking the nociceptin / orphanin FQ receptor Ahmadi S, Kotalla C, Guhring H, Takeshima H, Pahl A, Zeilhofer HU Molecular Pharmacology 2022。 10: 1537 ? Present in human nervous system ? Different NST forms ? Animal models 人 ,大鼠 ,小鼠大腦及人腦脊液中痛穩(wěn)素的鑒別 存在于人類的神經(jīng)系統(tǒng)中 痛穩(wěn)素的不同結(jié)構(gòu) 動(dòng)物模型 Lee TL et al. 1999 Pathophysiological roles of the two isoforms of nocistatin in pain perception: parison of bioactivities between nocistatin17 and nocistatin30 Meng MJ. 2022。 Nociceptin ? Nociceptin ligand for orphan opioid receptor ? Nocistatin – functional antagonist ? Identify precursors ? Sequence bioactive derivatives ? Establish the active fraction OkudaAshitaka E, Tachibana S et al, Nocistatin, a peptide that blocks nociceptin action in pain transmission Nature 1998 Lee TL, Tachibana S. Nocistatin – a new antinociceptive peptide. Regional Anesthesia amp。 21:104750 NST (future) ? NST receptor(s) ? Antagonists / agonists ? Correlate with specific disease state 痛穩(wěn)素 (前景 ) 痛穩(wěn)素受體 拮抗劑 /激動(dòng)劑 與特異疾病的相關(guān)性
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