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Tat Leang LEE Department of Anaesthesia Yong Loo Lin School of Medicine National University of Singapore Advances in Amino Acids and Neuropeptides Research and Pain 關(guān)于氨基酸和神經(jīng)肽與疼痛關(guān)系的研究 Rational treatment of pain requires identification of pain mechanisms as targets of drug therapy 致病因素 臨床實(shí)體 疾病機(jī)制 癥狀體征 疼痛機(jī)制 基于疼痛機(jī)制的治療 與疼痛相關(guān)的癥狀體征 特定機(jī)制結(jié)果的評(píng)測(cè) Rational treatment of pain requires identification of pain mechanisms as targets of drug therapy 致病因素 臨床實(shí)體 疾病機(jī)制 癥狀體征 疼痛機(jī)制 與疼痛相關(guān)的癥狀體征 基于疼痛機(jī)制的治療 特定機(jī)制結(jié)果的評(píng)測(cè) Key molecular elements in the transduction, transmission and signal processing of nociceptive input in the peripheral and central nervous system represent potential targets for the development of new analgesics. Mechanismbased pain diagnosis: issues for analgesic drug development Woolf CJ, Max MB. Anesthesiology 2022。95: 2419 Pain: moving from symptom control toward mechanismspecific pharmacologic management Woolf CJ. Ann Intern Med. 2022。140:4415 Can we conquer pain? Schol J, Woolf CJ. Nature neuroscience suppl. 2022。5:10627 基于病理機(jī)制的疼痛診斷 : 鎮(zhèn)痛藥發(fā)展的問(wèn)題 我們能否征服疼痛 ? 疼痛 : 從癥狀控制向特異機(jī)制的藥理學(xué)治療轉(zhuǎn)移 Background 背景 ? Cerebral spinal fluid (CSF) reflects metabolic state of brain 腦脊液反映疼痛的新陳代謝狀態(tài) ? Analysis of CSF amino acids and peptides – highly relevant in pain perception and also neurological diseases 腦脊液中氨基酸和縮氨酸與疼痛感知和神經(jīng)系統(tǒng)疾病高度相關(guān) ? Chronic Pain – inflammatory, neuropathy and cancer 慢性疼痛分類(lèi) —發(fā)炎 , 神經(jīng)系病 , 癌癥 ? Mechanisms very challenging and not yet understood 對(duì)于疼痛機(jī)制 , 目前還沒(méi)有被足夠的了解 , 非常具有挑戰(zhàn)性 ? Lack of effective therapeutics 缺乏有效的治療法 Background ? Excitatory and inhibitory amino acids and also nitric oxide (NO) are involved in pain modulation. 興奮性 , 抑制性氨基酸和一氧化氮涉及到對(duì)疼痛的調(diào)節(jié) ? Neuropeptides are implicated in pain modulation. 神經(jīng)肽影響對(duì)疼痛的調(diào)節(jié) Objectives A two pronged study on CSF 對(duì)腦脊液的兩次研究 ? To quantitatively analyze physiological amino acids and pain related pounds in CSF samples from pain patients 對(duì)疼痛病人腦脊液中生理氨基酸和疼痛相關(guān)的化合物定量研究 ? To find new painrelated peptides (molecular mass 15,000 Da) from CSF samples of chronic pain patients 從慢性疼痛病人的腦脊液中尋找與疼痛相關(guān)的肽 ( 分子量小于15000) ? Results should lead to better understanding of pain mechanisms and new treatment strategy 實(shí)驗(yàn)結(jié)果幫助我們更深的了解疼痛機(jī)制和尋找新的治療方法 Amino acids in CSF and Pain 腦脊液中氨基酸和疼痛關(guān)系的研究 液相色譜法對(duì)生理氨基酸在未被預(yù)處理的腦脊液中的定量測(cè)量 Typical Chromatogram典型色譜層析圖 ? STD AA 氨基酸分離標(biāo)準(zhǔn)圖 1aspartate天 (門(mén) )冬氨酸鹽 2glutamate 谷氨酸 3asparagine天冬酰胺酸 4glutamine谷酰胺 5citrulline瓜氨酸 6serine絲氨酸 7threonine蘇氨酸 8glycine甘氨酸 9alanine丙胺酸 10arginine精氨酸 11taurine?;撬? 12GABA伽馬氨基丁酸 13proline脯氨酸 14valine纈氨酸 15methionine蛋氨酸 16isoleucine異亮氨酸 17leucine亮氨酸 18tryptophan色氨酸 19phenylalanine苯基丙氨酸 20cystine胱氨酸 21Ammonia氨 22lysine賴(lài)氨酸 23histidine組氨酸 24tyrosine酪氨酸 1aspartate天 (門(mén) )冬氨酸鹽 2glutamate 谷氨酸 3asparagine天冬酰胺酸 4glutamine谷酰胺 5citrulline瓜氨酸 6serine絲氨酸 7threonine蘇氨酸 8glycine甘氨酸 9alanine丙胺酸 10arginine精氨酸 11taurine?;撬? 12GABA伽馬氨基丁酸 13proline脯氨酸 14valine纈氨酸 15methionine蛋氨酸 16isoleucine異亮氨酸 17leucine亮氨酸 18tryptophan色氨酸 19phenylalanine苯基丙氨酸 20cystine胱氨酸 21Ammonia氨 22lysine賴(lài)氨酸 23histidine組氨酸 24tyrosine酪氨酸 ? CSF sample Salient features of the method 方法特色 ? Use of Triton X100 ( Triton X100 的應(yīng)用) ? No pretreatment of CSF 腦脊液不被預(yù)處理 ? Enhanced recovery of hydrophilic amino acids 提高親水性氨基酸的恢復(fù) ? Detection of cit