P2X3受体在大鼠慢性炎性痛中的作用

P2X3受体表达于感觉神经元,为配体门控离子通道受体,在外周疼痛的伤害性信息传递及痛敏产生中起重要作用[1].有研究表明,P2X3受体参与了大鼠神经病理性痛[2].本研究拟探讨脊髓P2X3受体在大鼠慢性炎性痛中的作用.材料与方法     

背根神经节P2X3受体在大鼠切口痛形成中的作用

目的 评价背根神经节P2X3受体在大鼠切口痛形成中的作用.方法 健康雄性SD大鼠24只,体重200～220 g,随机分为3组(n=8):对照组(C组)、切口痛组(IP组)和P2X3受体拮抗剂组(A组).IP组和A组制备大鼠左后趾部切口痛模型.模型建立后30 min,A组左后爪底皮下注射P2X3受体特异性拮抗剂TNP-ATP 200 nmol,C组和IP组注射等容量生理盐水.采用累积疼痛评分法,评定注药后1 h内大鼠疼痛行为学变化.注药后2 h时处死大鼠,取背根神经节,测定P2 X3受体表达和细胞内Ca2+浓度.结果 与C组比较,IP组和A组累积疼痛评分和Ca2+浓度升高,P2X3受体表达上调(P＜0.05);与IP组比较,A组累积疼痛评分和Ca2+浓度降低,P2X3受体表达下调(P＜0.05).结论 背根神经节P2X3受体参与了大鼠切口痛的形成,其机制可能与升高细胞内Ca2+浓度有关.     

P2X3受体介导急性痛反应大鼠脊髓背角星形胶质细胞P物质受体和谷氨酸受体表达的变化

P2X3受体在背根感觉神经节特异表达,参与疼痛的信号传递.大鼠足底注射ATP等P2X3受体激动剂可诱发急性伤害性反应[1].研究表明,疼痛的发生和维持不仅与神经元有关,脊髓胶质细胞在某些因素诱导下,也参与了疼痛产生的过程[2],而其是否参与了由P2X3受体介导的急性疼痛信号传导,目前尚不清楚.本研究拟评价P2X3受体介导急性痛反应大鼠脊髓背角星形胶质细胞内P物质受体NK-1和谷氨酸受体NMDA1表达的变化,以探讨脊髓背角星形胶质细胞在急性痛信号传导中的作用.     

小胶质细胞与三磷酸腺苷在疼痛中的作用

大量证据表明,细胞内外三磷酸腺苷(adenosine 5'-triphosphate,ATP)在疼痛信号转导中起着重要作用.目前研究主要集中在ATP及其受体在慢性疼痛(尤其是神经病理性疼痛)中的作用及其可能机制.机体受到刺激后,激活的小胶质细胞会高表达P2X4受体和其他ATP受体,从而释放脑源性生长因子(brain-derived neurotrophic factor,BDNF)、白介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-a,TNF-α)和一氧化氮(nitric oxide,NO).了解这些ATP受体的重要作用将为慢性疼痛治疗提供新的策略.     

脊髓P2X4受体在糖尿病大鼠神经病理性痛中的作用

目的探讨脊髓P2X4受体在链脲菌素诱导的糖尿病大鼠神经病理性痛中的作用。方法雄性Wistar大鼠84只,3月龄,体重180～220 g,随机分为2组（n=42）：对照组（C组）和糖尿病神经病理性痛组（D组）。C组单次腹腔注射等体积（3.25 ml/kg）枸橼酸缓冲液,D组单次腹腔注射链脲菌素65 mg/kg制备糖尿病模型。2组分别于给药前1 d（基础值）、给药后3、7、14、21、28 d各随机选取7只大鼠,测定机械缩足阈值和热痛阈潜伏期,痛阈测定后断头处死大鼠,取L（4,5）脊髓组织,用RT-PCR方法测定P2X4受体mRNA表达水平。结果与C组相比,D组脊髓P2X4受体mRNA表达上调,机械缩足阈值降低（P〈0.05）,热痛阈潜伏期差异无统计学意义（P〉0.05）;与基础值比较,D组给药后14 d机械缩足阈值逐渐降低,给药后28 d时达最低值;给药后3 d脊髓P2X4受体mRNA表达逐渐上调,给药后7d达峰值（P〈0.05）。结论脊髓P2X4受体表达上调参与了糖尿病大鼠神经病理性痛的发生。     

微小RNA在病理性疼痛中的作用

背景 微小RNA(microRNAs,miRNAs)是目前研究最为广泛的一类内源性非编码小分子RNA,长度范围在16～29个核苷酸之间,通过转录后调节机制调节基因的表达.最近研究发现miRNAs在不同的病理性疼痛模型中均有不同程度的表达,可能参与慢性疼痛以及急性伤害性刺激伤害感受过程的基因调节机制,调控几种与疼痛相关转录物的表达. 目的 对miRNAs在病理性疼痛中作用的研究有助于我们更清楚地了解病理性疼痛的产生和维持分子学机制,为疼痛治疗提供了新的方向. 内容 主要介绍miRNAs在炎症性痛、神经病理性痛以及疼痛相关性疾病中的表达情况,以及miRNAs在慢性病理性疼痛中的可能作用. 趋势 鉴于miRNAs在病理性疼痛的产生中具有重要作用,miRNAs将有可能作为治疗疼痛性疾病的一种新型的研究工具、生物标记和潜在的药物治疗靶点.     

氯胺酮与可乐定对神经病理性痛大鼠脊髓P2X4R mRNA表达的影响

目的 评价氯胺酮与可乐定对神经病理性痛大鼠脊髓P2X4受体mRNA(P2X4R mRNA)表达的影响.方法 雄性SD大鼠80只,体重180～220 g,随机分为假手术组(S组)、神经病理性痛组(NP组)、氯胺酮组(K组)、可乐定组(CL组)和氯胺酮+可乐定组(KC组),每组16只.采用坐骨神经慢性压迫(CCI)法制备大鼠神经病理性痛模型.K组、CL组、KC组于CCI后3～21 d每天分别腹腔注射氯胺酮10 mg/kg、可乐定1 mg/kg和氯胺酮5 mg/kg+可乐定0.5 mg/kg.S组和NP组腹腔注射等容量生理盐水.分别于CCI前1 d、CCI后3、7、14和21 d且腹腔注射前,随机取4只大鼠,测定机械痛阈和热痛阈,并于CCI前1 d、CCI后7、14和21 d痛阈测定结束后断头处死,测定脊髓P2X4R mRNA表达水平.结果 与CCI前1 d比较,CCI后S组热痛阈、机械痛阈和脊髓P2X4R mRNA表达差异无统计学意义(P>0.05),其余4组热痛阈和机械痛阈降低,脊髓P2X4R mRNA表达上调(P<0.05);与NP组比较,K组、CL组、KC组CCI后热痛阈及机械痛阈升高,脊髓P2X4R mRNA表达下调(P<0.05);与K组比较,KC组CCI后热痛阈和机械痛阈升高,脊髓P2X4R mRNA表达下调(P<0.05),CL组上述指标差异无统计学意义(P>0.05).结论 氯胺酮与可乐定减轻大鼠神经病理性痛的机制可能与下调脊髓P2X4R mRNA的表达有关.     

滥用氯胺酮引起膀胱功能障碍患者膀胱组织中P2X1受体的表达及其意义

目的 研究P2X1受体在滥用氯胺酮导致膀胱功能障碍患者膀胱组织中的表达及其临床意义.讨论P2X1受体在滥用氯胺酮引起膀胱功能障碍中的作用.方法 采用免疫组织化学方法分别检测36例滥用氯胺酮引起膀胱功能障碍患者(实验组)和36例正常膀胱组织(对照组)中P2X1受体、M2受体、M3受体的表达情况,利用全自动显微镜及图像分析系统对免疫组化染色结果进行图像采集分析、测量其平均灰度值,同时比较两组间P2X1受体、M2受体、M3受体表达的差异.结果 P2X1受体主要在膀胱黏膜移行上皮细胞表达,实验组P2X1受体表达明显增强,与对照组比较差异有统计学意义(P＜0.01),而M2受体、M3受体表达与对照组比较无明显差异(P＞0.01).结论 滥用氯胺酮引起膀胱功能障碍患者膀胱组织中P2X1受体表达显著增强,而M2受体、M3受体并未异常表达,提示P2X1受体上调可能在滥用氯胺酮导致膀胱过度活动中发挥关键作用.     

痛情绪的神经回路及其机制研究进展

背景 疼痛是一种复杂的主观感觉和情绪体验,包括感觉分辨组分和情绪动机组分.目前,对痛感觉分辨的机制已有了较为深入的认识,但是痛情绪动机组分的具体机制仍不清楚. 目的 探讨痛情绪组分的中枢神经调控及其机制.内容 分别从痛情绪组分调控相关的前扣带回皮质、杏仁核、终纹床核等几方面阐述了痛情绪的神经回路及其机制研究进展.趋向 慢性病理性疼痛常常伴有心理和情绪功能障碍,研究痛情绪的神经回路及其分子机制对于慢性疼痛的治疗具有重要临床意义.     

电针对神经病理性疼痛大鼠脊髓P2X3受体表达的影响

目的 探讨电针对神经病理性疼痛大鼠脊髓P2X3受体表达的影响.方法 清洁级雄性SD大鼠60只,体重180 g～220 g,采用随机数字表法分为6组,每组10只:假手术组(Sham组)仅分离坐骨神经,不结扎;神经病理性疼痛组(CCI组)采用坐骨神经慢性压迫性损伤法制备神经病理性疼痛模型;2 Hz穴位电针组(LEA组)于坐骨神经结扎(chronic constrictive injury,CCI)后第4天开始电针治疗,刺激大鼠术侧足三里-阳陵泉穴,频率2 Hz连续波,强度≤1.5 mA,每天1次,30 min/次,连续6d;15 Hz穴位电针组(HEA组)电针频率为15 Hz,余同LEA组;2 Hz非穴位电针组(NA-LEA组)电针刺激大鼠术侧足三里-阳陵泉旁5mm非穴位点,余同LEA组;15 Hz非穴位电针组(NA-HEA组)电针刺激大鼠术侧足三里-阳陵泉旁5mm非穴位点,余同HEA组.各组术前1 d(T0)和术后3、5、7、9 d(T1-4)测定大鼠后肢机械缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足反射潜伏期(thermal withdrawal latency,TWL);于术后第10天处死大鼠,取右侧L4-6脊髓节段,Western-blot和反转录酶-聚合酶链锁反应法分别检测大鼠脊髓P2X3受体蛋白和mRNA表达.结果 与Sham组比较,其余各组MWT和TWL降低(P＜0.05),脊髓P2X3受体蛋白和mRNA表达升高(P＜0.05);与CCI组比较,LEA组和HEA组T2-4时MWT和TWL升高(P＜0.05),脊髓P2X3受体蛋白和mRNA表达降低(P＜0.05);与LEA组比较,T4时HEA组MWT和TWL升高,脊髓P2X3受体蛋白和mRNA表达增多(P＜0.05).结论 电针足三里-阳陵穴可明显增加神经病理性疼痛大鼠的机械痛和热痛阈值,其机制可能与降低脊髓背角P2X3受体表达有关.     

Opioid responsiveness

Cancer pain generally responds in a predictable way to analgesic drugs and drug therapy is the mainstay of treatment. A small proportion of patients, of the order of 20%, have pain that does not respond well to conventional analgesic management. Because opioid analgesics are the most important part of this pharmacological approach, a terminology has developed which centres around whether or not pain will respond to opioid analgesics. The terms opioid-responsive-pain and opioid-non-responsive pain, or opioid-resistant-pain, have been used to differentiate between patients whose pain falls into these two broad groups. This terminology is not satisfactory because it implies an all or none phenomenon, that is that pain either does or does not respond to opioid analgesics. Rarely is there such a clear distinction in practice. This is because the end point when titrating dose against pain with strong opioid analgesics is not simply pain relief or lack of relief: adverse effects may limit dose titration. It is preferable to describe patients with pain which is relatively less sensitive to opioids and/or patients where there is an inbalance between analgesia and unwanted effects as having “opioid-poorly-responsive pain”. A pragmatic definition of opioid-poorly-responsive pain is pain that is inadequately relieved by opioid analgesics given in a dose that causes intolerable side effects despite routine measures to control them. Included in this definition is so called paradoxical pain which is not a distinct entity. Neuropathic pain is the most common form of opioid-poorly-responsive pain. The underlying pathophysiology remains unclear but abnormal metabolism of morphine is not the cause of a poor response to this drug. Patients with opioid-poorly-responsive-pain should be considered for treatment with the same opioid by an alternative (spinal) route or with an alternative opioid agonist administered by the same route (whether oral or parenteral), in conjunction with adjuvant analgesics such as tricyclic antidepressants. The most commonly used alternative oral opioids are phenazocine and methadone; transdermal fentanyl is an additional option.     

Paediatric chronic pain

Many children and adolescents experience chronic pain at some point in their childhood. While the majority may be successfully supported by their local services, some may develop persistent pain-related functional disability that should prompt referral to a multidisciplinary paediatric pain service for assessment. These teams work with the family to provide a framework for promoting rehabilitation and restoration of function based on the biopsychosocial model. Mental health difficulties including psychological trauma are often a significant factor. Individualized therapeutic work is core to the pain management pathway. Medications and therapeutic injections are used less frequently in children compared to adult practice but may have a role in facilitating rehabilitation as part of a multidisciplinary approach.     

Medicines optimization in acute and chronic pain

Pain is a complex condition and warrants a multidisciplinary approach based on a bio-psycho-social model. Whilst often successful in acute pain, pharmacological treatment is rarely successful on its own in the management of chronic pain due to the high number of patients needed to treat to achieve a clinically meaningful improvement in function, quality of life and pain scores. There are also significant side effects in the short and long term. Recent re-analysis of clinic trial data focused on individual responder rates, showed that there is a cohort of patients who achieve 50% pain relief with subsequent improvement in physical function. To avoid intolerable side effects from medication used for chronic pain, titration needs to be slow and aimed towards the agreed risk–benefit between patients and treating physician with a clear plan for weaning and cessation if these goals are not achieved. Pain-orientated physiotherapy, either on its own or as part of a pain management programme, should be offered and medication reduced or weaned after restoration of function has been achieved.     

Rhetoric and reality on acute pain services in the UK: a national postal questionnaire survey

Background. The study aimed to explore the extent to which NHSacute pain services (APSs) have been established in accordancewith national guidance, and to assess the degree to which cliniciansin acute pain management believe that these services are fulfillingtheir role. Methods. A postal questionnaire survey addressed to the headof the acute pain service was sent to 403 National Health Servicehospitals each carrying out more than 1000 operative proceduresa year. Results. Completed questionnaires were received from 81% (325)of the hospitals, of which 83% (270) had an established acutepain service. Most of these (86%) described their service asMonday–Friday with a reduced service at other times; only5% described their service as covering 24 hours, 7 days a week.In the majority of hospitals (68%), the on-call anaesthetistwas the sole provider of out of hours services. Services werecategorized by respondents as thriving (30%), struggling tomanage (52%) or non-existent (17%). There was widespread agreement(     

The post-operative painful knee—Clinical and societal causation

Persistent post-surgical pain (PPSP) remains a problem after knee replacement. “Pain” is not likely to be monolithic or a single entity. It can broadly be divided into mechanical pain that is not continuous and is influenced by movement and non-mechanical pain, which is continuous and is marginally affected by activity. If the cause of mechanical pain can be identified, corrective surgery may help.Non-mechanical pain can be subdivided into three groups as follows: sepsis, neuropathic, and perceived pain. The first two groups can be treated to some extent, but the perceived pain group that is very heterogeneous, remains a significant problem.     

The future role of the anaesthesiologist in pain management

Background: Relieving pain during and after surgery and trauma has always been a basic duty of anaesthesiologists. With their skills and expertise in regional analgesia and pharmacological analgesia, anaesthesiologists have improved management of severe cancer pain. Will there be a place for anaesthesiologists in multidisciplinary pain clinics managing chronic non‐cancer pain patients in the future? Methods: This is a personal review of the development of pain management as a growing part of the responsibilities of anaesthesiologists during the past three decades and the importance of continued involvement of anaesthesiologists in this interesting and challenging aspect of clinical medicine. Results and conclusions: Optimal management of pain during and after surgery is a prerequisite for successful short‐ and long‐term rehabilitation after surgery. After surgery, reducing dynamic pain with prolonged optimal epidural analgesia and regional blocks facilitates mobilization and reduces chronic pain. The expertise of well‐trained anaesthesiologists in skilfully using regional analgesia and pharmacological pain relief continues to be in demand in palliative care. Some interventional techniques are useful in relieving chronic non‐cancer pain in selected patients. Well‐trained anaesthesiologist‐pain clinicians can perform interventional treatments safely. No doubt, anaesthesiologists will continue to have important roles in pain management in the future.